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.

Echocardiography: conotruncal anomaly: a case of common arterial trunk with intact ventricular septum and hypoplastic left heart complex with unbalanced pulmonary stenoses.

We describe the echocardiographic findings of a common arterial trunk with intact ventricular septum, mitral and left ventricular hypoplasia, atretic left ventricular outlet and bilateral, and unbalanced pulmonary artery stenoses.

Cardiovascular magnetic resonance pulmonary perfusion for guidance of interventional treatment of pulmonary vein stenosis.

BACKGROUND: Pulmonary vein (PV) stenosis represents a rare but serious complication following radiofrequency ablation of atrial fibrillation with a comprehensive diagnosis including morphological stenosis grading together with the assessment of its functional consequences being imperative within the relatively narrow window for therapeutic intervention. The present study determined the clinical utility of a combined, single-session cardiovascular magnetic resonance (CMR) imaging protocol integrating pulmonary perfusion and PV angiographic assessment for pre-procedural planning and follow-up of patients referred for interventional PV stenosis treatment. METHODS: CMR examinations (cine imaging, dynamic pulmonary perfusion, three-dimensional PV angiography) were performed in 32 consecutive patients prior to interventional treatment of PV stenosis and at 1-day and 3-months follow-up. Degree of PV stenosis was visually determined on CMR angiography; visual and quantitative analysis of pulmonary perfusion imaging was done for all five lung lobes. RESULTS: Interventional treatment of PV stenosis achieved an acute procedural success rate of 90%. Agreement between visually evaluated pulmonary perfusion imaging and the presence or absence of a ≥ 70% PV stenosis was nearly perfect (Cohen's kappa, 0.96). ROC analysis demonstrated high discriminatory power of quantitative pulmonary perfusion measurements for the detection of ≥ 70% PV stenosis (AUC for time-to-peak enhancement, 0.96; wash-in rate, 0.93; maximum enhancement, 0.90). Quantitative pulmonary perfusion analysis proved a very large treatment effect attributable to successful PV revascularization already after 1 day. CONCLUSION: Integration of CMR pulmonary perfusion imaging into the clinical work-up of patients with PV stenosis allowed for efficient peri-procedural stratification and follow-up evaluation of revascularization success.

Performance of pacemaker leads in alternative lead positions after tricuspid valve replacement.

BACKGROUND: Bradycardic arrhythmias requiring pacemaker (PM) implantation are still common in patients in need of tricuspid valve replacement (TVR). Leaving an existing PM lead in an extravalvular position may represent a helpful alternative in special situations like the implantation of a mechanical TV. This study aimed to examine the short- to mid-term outcome of paravalvular leads concerning lead survival and prosthesis dysfunction in patients after TVR. METHODS: A retrospective case-control study of patients with TVR and ventricular pacing was conducted. Patients from the database of the Leipzig Heart Center were included. Data of the paravalvular lead group (PVG) and coronary sinus lead group (CSG) were compared to a control group with conventional transvalvular leads (TVG). RESULTS: Eighty patients with TVR and cardiac PM (TVG [n = 13], PVG [n = 40], and CSG [n = 27]) were included. The mean follow-up was 2.8 years. The rate of lead revisions (TVG 15.4%, PVG 2.5%, and CSG 7.5%) was lower in PVG but without significance (P = .286). The CSG demonstrated significantly higher pacing thresholds (1.4 V/0.8 ms) than TVG (0.5 V/0.4 ms), P = .004. However, the deterioration of threshold amplitudes during follow-up was similar in CSG (7.4%) and PVG (7.5%) compared with controls (7.7%). Function of TV prosthesis regarding development of stenosis or regurgitation showed a similarity between the groups (regurgitation PVG P = .692, CSG P = 1; stenosis PVG P = .586, CSG P = 0.69). CONCLUSION: Paravalvular positioning of PM leads seems to represent a reasonable alternative to the conventional transvalvular lead positioning concerning the lead and Tricuspid Valve prosthesis's function and durability in selected patients.

Closure of Secundum Atrial Septal Defects by Using the Occlutech Occluder Devices in More Than 1300 Patients: The IRFACODE Project: A Retrospective Case Series.

BACKGROUND: The Occlutech Figulla ASD device series (OFSO) shows an improved device design for interventional ASD closure, larger follow-up series are missing. METHODS: We retrospectively reviewed the feasibility, safety, implantation properties, results, and follow-up of ASD closure using Occlutech devices over a 5 year period by establishing a multi-institutional collaborative result registry with 16 contributing centers from 11 countries (IRFACODE). RESULTS: In 1315 patients of all age groups (female 66.9%), successful (98%) ASD closure was performed (mean age 28.9 years, weight 52 kg, height 148.6 cm). Of the defects, 47.9% showed no or only a deficient aortic rim; in 11.9%, there was more than one defect; a septum aneurysm was present in 21.5%; and the mean implanted device size was 20.5 mm. Immediate closure was achieved in 78.6%, at discharge in 83.1%, and 96.4% and 97.3% at 6 and 12 months follow-up, respectively. During a mean follow-up of 2.7 years (in total 3597 patient years), significant complications were minimal (total = 8, <1%) with secondary device embolizations in five and AV-blocks in three patients. No erosion or death was reported. CONCLUSION: ASD closure using OFSO is feasible in a large variety of patients, safe with only a minimal risk of severe side effects and especially without any aortic erosions despite a large percentage of large and complicated defects. © 2016 Wiley Periodicals, Inc.

Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate-Rapid Tumor Regression Documented by Real Time 3D Echocardiography.

The presented case reports on successful treatment with everolimus in a neonate with left ventricular giant rhabdomyoma. The authors used a different dosage regime compared to literature and documented rapid tumor regression by 3D echocardiography.

Specific Morphology of Coronary Artery Aneurysms in Mainly White Patients With Kawasaki Disease: Initial Data From the Cardiac Catheterization in Kawasaki Disease Registry.

BACKGROUND: Patients with Kawasaki disease (KD) with coronary artery involvement require long-term cardiac care. Although respective evidence-based recommendations are missing, cardiac catheterization is still considered the gold standard for diagnosing detailed coronary pathology. Therefore, to better understand coronary artery pathology development, we conducted a survey to document and evaluate cardiac catheterization data in a European population. METHODS AND RESULTS: We retrospectively analyzed cardiac catheterization data from KD children from the year 2010 until April 2023. This registry covers basic acute-phase clinical data, and more importantly, detailed information on morphology, distribution, and the development of coronary artery pathologies. A total of 164 mainly White patients (65% boys) were included. A relevant number of patients had no coronary artery aneurysm (CAA) at the cardiac catheterization, indicating that distal CAAs were almost exclusively detected alongside proximal CAAs. Patients with multiple CAAs revealed a significant positive correlation between the number of CAAs and their dimensions in diameter and in length. Location of the CAA within the coronary artery, age at onset of KD, or natal sex did not significantly influence CAA diameters, but CAAs were longer in older children and in boys. CONCLUSIONS: That distal CAAs were only present together with proximal ones will hopefully reduce diagnostic CCs in patients with KD without echocardiographically detected proximal CAAs. Furthermore, this study gives valuable insights into dimensional specifics of CAAs in patients with KD. As an ongoing registry, future analyses will further explore long-term outcomes and performed treatments, helping to refine clinical long-term strategies for patients with KD. REGISTRATION: URL: https://drks.de/; Unique Identifier: DRKS00031022.

Odd acoustic window and elongated ventricles: echocardiographic diagnosis of congenital absence of the pericardium.

A 14-year-old boy with a heart murmur was referred to the authors' department because structural heart disease could not be ruled out by standard echocardiographic views. The best apical four-chamber view was obtained with the patient turned to a right lateral decubitus position and the transducer shifted almost to the posterior axillary line. A biplane chest x-ray also showed a counterclockwise heart axis deviation. Magnetic resonance imaging confirmed the suspected congenital absence of the pericardium.

Echocardiographic detection of coronary air embolism as the cause of cardiac arrest in a neonate with transposition of the great arteries.

A hemodynamically stable neonate with transposition of the great arteries suddenly went into cardiac arrest during preparation for transport to the operating room. Emergency echocardiography during cardiac massage detected coronary air embolism as the presumed cause of arrest. After about 15 minutes of resuscitation, it was possible to establish return of spontaneous circulation. Since the most likely source of air was the neonate's peripheral venous line, we have introduced inline microfilters for all neonates and all patients with right-to-left shunt lesions and did not encounter proven air embolism thereafter.

A case report: Amplatzer occluder device closure of an iatrogenic ventricular septal defect following radiofrequency ablation.

BACKGROUND: Interventricular septal perforation is an extremely rare complication of radiofrequency ablation (RFA), with an incidence of 1%. The most common mechanism is a 'steam pop', which can be described as 'mini-explosions' of gas bubbles. Data for percutaneous repair of cardiac perforations due to RFA are limited. CASE SUMMARY: A 78-year-old female patient was referred to our department for the treatment of two iatrogenic ventricular septal defects (VSDs) following radiofrequency ablation (RFA) of premature ventricular contractions. One week post-ablation, chest pain and progressive dyspnoea occurred. Transthoracic echocardiography detected a VSD, diameter 10 mm. Hence, iatrogenic, RFA-related myocardial injury was considered the most likely cause of VSD, and the patient was referred to our tertiary care centre for surgical repair. Cardiovascular magnetic resonance (CMR) imaging demonstrated border-zone oedema of the VSD only and confirmed the absence of necrotic tissue boundaries, and the patient was deemed suitable for percutaneous device closure. Laevocardiography identified an additional, smaller muscular defect that cannot be explained by analysing the Carto-Map. Both defects could be successfully closed percutaneously using two Amplatzer VSD occluder devices. DISCUSSION: In conclusion, this case demonstrates a successful percutaneous closure of a VSD resulting from RFA using an Amplatzer septal occluder device. CMR might improve tissue characterization of the VSD borders and support the decision if to opt for interventional or surgical closure.

Effectiveness of neonatal pulse oximetry screening for detection of critical congenital heart disease in daily clinical routine--results from a prospective multicenter study.

Pulse oximetry screening (POS) has been proposed as an effective, noninvasive, inexpensive tool allowing earlier diagnosis of critical congenital heart disease (cCHD). Our aim was to test the hypothesis that POS can reduce the diagnostic gap in cCHD in daily clinical routine in the setting of tertiary, secondary and primary care centres. We conducted a prospective multicenter trial in Saxony, Germany. POS was performed in healthy term and post-term newborns at the age of 24-72 h. If an oxygen saturation (SpO(2)) of

Physiologic effects and functional outcome after treatment of dysfunctional right ventricular outflow tract in congenital heart disease using a two-stage intervention.

BACKGROUND: Pathophysiological differences in relief of pulmonary stenosis (PS) as opposed to pulmonary regurgitation (PR) by percutaneous pulmonary valve implantation (PPVI) remain elusive, but might impact current assessment of procedural success and ultimately indications. METHODS: Invasive pressure measurements, cardiac magnetic resonance imaging and cardiopulmonary exercise testing were performed before pre-stenting (BMS), after BMS and after PPVI in patients with either PS or PR. RESULTS: In PS (n = 14), BMS reduced the right ventricular (RV) to systemic pressure ratio (0.8 ± 0.2 vs. 0.4 ± 0.1%; p < .01), improved RF EF (53 ± 14 vs. 59 ± 12%; p = .01) but introduced free PR (PR fraction post 39 ± 12%; p < .01) with no changes in effective RV stroke volume (SV). PPVI eliminated PR (PR fraction 5 ± 3%; p < .01) and improved effective RV SV (p < .01) with no changes in RV EF (p = .47). Peak VO2 improved significantly after BMS, with no changes following PPVI (26 ± 9 vs. 30 ± 11 vs. 31 ± 10 ml/kg*min). In PR (n = 14), BMS exaggerated PR (PR fraction post 47 ± 10) with reduction in effective RV SV (pre 43 ± 9 vs. post 38 ± 8 ml/m2; p = .01), which improved after PPVI (post PPVI 49 ± 9 ml/m2; p < .01), secondary to elimination of PR (PR fraction 5 ± 4%; p < .01). RV EF (pre 53 ± 11 vs. post 53 ± 9 vs. post PPVI 50 ± 9%) and Peak VO2 (pre 22 ± 7 vs. post 21 ± 7 vs. post PPVI 23 ± 7 ml/kg*min) remained unchanged. CONCLUSIONS: Exercise capacity in patients with right ventricular outflow tract dysfunction is primarily afterload-dependent.

Transcatheter aortic valve closure to treat severe aortic regurgitation in a patient failing stage I palliation for hypoplastic left heart syndrome.

We present a patient with borderline left ventricle, in whom significant aortic regurgitation after failed attempt of biventricular repair with balloon valvuloplasty and consecutive Norwood stage 1 procedure substantially contributed to persisting hemodynamic instability. Transcatheter closure of the aortic valve using an Amplatzer(R) septal occluder was performed and led to clinical stabilization. At medium-term follow-up, there was neither residual aortic regurgitation nor obstruction of the coronary artery origins.

Pulse Oximetry Screening in Germany-Historical Aspects and Future Perspectives.

In January 2017, pulse oximetry screening was legally implemented in routine neonatal care in Germany. The preceding developments, which were the prerequisite for this step, are described in the specific context of Germany's health care system. Continued evaluation of the method is imperative and may lead to modifications in the screening protocol, ideally in accordance with the efforts in other countries.

Lung Abscess as Delayed Manifestation of Pulmonary Arterial Narrowing After Sleeve Resection.

A patient who had undergone right upper bilobectomy because of a carcinoid experienced lung abscesses 17 months after operation. After recurrences, despite different antibiotic agents, dual-energy computed tomography showed subtotal stenosis of the right lower lobe pulmonary artery with marked pulmonary perfusion-reduction. Rare causes of lung-abscesses should be considered.

Emergency Covered Stent Implantation For Rupture Of A Pulmonary Vein After Balloon Angioplasty For Postinterventional Pulmonary Vein Stenosis.

Pulmonary vein (PV) stenosis is a known complication of PV isolation procedures for atrial fibrillation. We describe in this report a case of emergency covered stent implantation for rupture of a PV after balloon angioplasty for postinterventional PV stenosis occlusion. Focus is on stent implantation and on a novel aspect of magnetic resonance imaging for postprocedural outcome evaluation. A focused review of the current literature regarding ongoing limitations of PV stenosis treatment is provided.

Stent implantation of left main coronary artery stenosis in an infant: Effective long-term treatment?

Coronary artery stenosis is a rare phenomenon in children. Coronary stent implantation is generally not considered a standard treatment option due to technical difficulties and potential complications in this group of patients. Nevertheless, several pediatric cases reporting successful implantation with acceptable short-term experiences have been described. The following case presents a successful stent implantation for left main coronary artery (LMCA) stenosis early after surgery for anomalous left coronary artery from pulmonary artery (ALCAPA) at the age of 6 months. The excellent mid-term results and notably the procedure's potential as a longterm treatment in small children are highlighted. A 6-month-old infant underwent surgery for ALCAPA. Due to sudden postoperative deterioration, cardiac catheterization was performed. Coronary angiography revealed severe (90%) ostial LMCA stenosis. A PROMUS drug-eluting stent (Promus Element AL3.0 × 8 mm, Boston Scientific, Natick, Massachusetts, USA) was implanted. The procedure was performed without complications. Antiplatelet therapy with acetylsalicylic acid and clopidogrel was initiated. Subsequently, cardiac function improved slowly. Cardiac catheterization 3 years 8 months after stent implantation showed no restenosis with a proximal LMCA diameter still at the 50(th) percentile for age. Neither were signs of heart failure reported at the last follow-up at 7 years of age. Presupposing normal growth, the implanted stent would thus provide sufficient myocardial perfusion with a LMCA lumen at the 40(th) percentile at the age of 16 years. In selected cases, coronary stent implantation may be an effective mid- to long-term treatment of coronary artery stenosis even in very young children.

Improved quality of life after treatment of prolonged asystole during breath holding spells with a cardiac pacemaker.

OBJECTIVES: To validate the physical and psychological effectiveness of cardiac pacing in pediatric patients with breath-holding spells (BHS) and prolonged asystole. MATERIALS AND METHODS: The records and clinical data of all the patients with BHS who presented to our center in the period of 2001-2013 were reviewed. All patients who received cardiac pacemaker implantation for prolonged asystole during BHS were included. In addition, the parents were asked to fill out a standardized quality of life (QOL) questionnaire. RESULTS: Seven patients were identified. The mean onset of symptoms was 7 month (1-12 months) of age, documented asystole was 12-21 seconds, and a permanent cardiac pacemaker device was implanted at a mean age of 23 months (8 months-3.9 years). No pacemaker related adverse events were recorded. Follow up showed immediate resolution from spells in four cases (4/7). Two patients (2/7) showed significant reduction of frequency and severity of spells, with complete elimination of loss of consciousness (LOC). One patient (1/7) with an additional neurologic disorder continued to have minor pallid BHS and eventually switched from pallid to cyanotic spells without further detection of bradycardia or asystole in holter examination. QOL questionnaire revealed significant reduction in subjective stress levels of patients (P = 0.012) and parents (P = 0.007) after pacemaker implantation. CONCLUSION: Cardiac pacing using appropriate pacemaker settings seems effective in the prevention of LOC and reduction of the frequency of BHS. Our results imply a reduction of subjective stress levels of patients and parents as well as an increased quality of everyday life. After all, randomized controlled trials of the influence of cardiac pacemaker implantation on subjective stress levels in patients with BHS are needed.

Performance of steroid eluting bipolar epicardial leads in pediatric and congenital heart disease patients: 15 years of single center experience.

OBJECTIVE: Cardiac pacing is sometimes required for patients with congenital heart disease for various reasons. Because of complex anatomy, repetitive previous heart surgery and patient size, epicardial leads are of special importance in these patients. Using epicardial leads has been discussed controversly regarding pacing performance and lead survival. The aim of this study was to review the long-term data on pacing performance as well as lead survival of epicardial leads implanted in our center. METHODS: Retrospective chart review and review of the literature. RESULTS: 82 consecutive pediatric patients or adult patients with congenital heart disease with 158 epicardial leads (Medtronic 4968, bipolar, steroid - eluting) were included. We found 1.2% pacemaker-related early postoperative complications. The incidence of lead dysfunction was 7.5% (12/158) for primary (i.e. directly related to the lead itself) lead dysfunction and 3.2% (5/158) of lead abandonment for reasons not directly related to the lead itself. Primary lead dysfunction occured after a median of 3.83 years. Lead survival at 2, 5 and 10 years was 98.7%, 93% and 92.4%. There were no infections reported. Stable median measurements for impedance (RA/RV/LV of 577/483/610 Ohm), sensing threshold (RA/RV/LV of 2.0/11.0/10.0 mV) and pacing threshold (RA/RV/LV of 0.75 V at 0.4 ms/1.0 V at 0.49 ms/1.0 V at 0.45 ms) indicated a good mid- to longterm performance. The only risk factor for primary lead dysfunction was young age at implantation. CONCLUSION: The use of epicardial leads in pediatric and adult patients with congenital heart disease shows good longterm outcomes in terms of pacing performance and lead survival. The authors encourage using epicardial leads in patients with congenital heart disease based on the patient's individual characteristics.