Sinus node dysfunction during transcatheter assessment and stent correction of sinus venosus atrial septal defects.

Covered stent correction of a superior sinus venosus atrial septal defect is increasingly performed as an alternative to surgical repair. While sinus node dysfunction requiring pacemaker implantation may be required after surgical repair, this has not been previously reported after covered stent implantation. We reviewed the experience in two interventional centers. Balloon inflation in the superior vena cava was used to confirm the anomalous pulmonary vein drainage would be unobstructed after stent implantation. During balloon testing in 62 consecutive patients, we assessed gradients across the pulmonary vein to left atrium while monitoring the rhythm. We observed the outcomes after covered stent correction in 51 patients. In a single patient, significant bradycardia and pauses developed on repeat balloon testing and the procedure was abandoned without stent implantation. In another patient, there was no sign of sinus node dysfunction during balloon testing but several hours after stent implantation, the patient became symptomatic from sinus bradycardia and pauses and had a pacemaker implanted 3 days later. Over a year later there are some signs of improvement in sinus node function. While sinus node dysfunction has not been described previously during balloon testing or after stent implantation, this report demonstrates for the first time that it may occur. Larger registries are therefore required to monitor for this uncommon complication.

Prevalence of cardiac valvar abnormalities in children and young people with autosomal dominant polycystic kidney disease.

BACKGROUND: Valvar abnormalities in children and adults with autosomal dominant polycystic kidney disease (ADPKD) have previously been reported as a frequent occurrence. Mitral valve prolapse (MVP), in particular, has been reported in almost one-third of adult patients and nearly 12% of children with ADPKD. Our objective in this study was to establish the prevalence of valvar abnormalities in a large, contemporary series of children and young people (CYP) with ADPKD. METHODS: A retrospective, single centre, cross-sectional analysis of the echocardiograms performed on all consecutive children seen in a dedicated paediatric ADPKD clinic. Full anatomical and functional echocardiograms were performed and analysed for valvar abnormalities. RESULTS: The echocardiograms of 102 CYP with ADPKD (range 0.25-18 years, mean age 10.3 years, SD ± 5.3 years) were analysed. One (0.98%), 3-year-old boy, had MVP. There was no associated mitral regurgitation. Evaluating variations in normal valvar anatomy, 9 (8.8%) patients, aged 7.1 to 18 years, had minor bowing ± visual elongation of either the anterior or posterior leaflet of the mitral valve, none of which fell within the criteria of true MVP. Three (1.9%) patients, 2 boys and 1 girl aged between 7 and 14 years, had trivial or mild aortic regurgitation. No patients had echocardiographic evidence of tricuspid valve prolapse (TVP). CONCLUSION: In this contemporary cohort of CYP with ADPKD, the incidence of MVP and other valvar lesions is significantly lower than previously reported. A higher resolution version of the Graphical abstract is available as Supplementary information.

3D Approaches in Complex CHD: Where Are We? Funny Printing and Beautiful Images, or a Useful Tool?

Echocardiography, CT and MRI have a crucial role in the management of congenital heart disease (CHD) patients. All of these modalities can be presented in a 2D or a 3D rendered format. The aim of this paper is to review the key advantages and potential limitations, as well as the future challenges of a 3D approach in each imaging modality. The focus of this review is on anatomic rather than functional assessment. Conventional 2D echocardiography presents limitations when imaging complex lesions, whereas 3D imaging depicts the anatomy in all dimensions. CT and MRI can visualise extracardiac vasculature and guide complex biventricular repair. Three-dimensional printed models can be used in depicting complex intracardiac relationships and defining the surgical strategy in specific lesions. Extended reality imaging retained dynamic cardiac motion holds great potential for planning surgical and catheter procedures. Overall, the use of 3D imaging has resulted in a better understanding of anatomy, with a direct impact on the surgical and catheter approach, particularly in more complex cases.

Visualization and Quantification of the Unrepaired Complete Atrioventricular Canal Valve Using Open-Source Software.

BACKGROUND: Repair of complete atrioventricular canal (CAVC) is often complicated by residual left atrioventricular valve regurgitation. The structure of the mitral and tricuspid valves in biventricular hearts has previously been shown to be associated with valve dysfunction. However, the three-dimensional (3D) structure of the entire unrepaired CAVC valve has not been quantified. Understanding the 3D structure of the CAVC may inform optimized repair. METHODS: Novel open-source work flows were created in SlicerHeart for the modeling and quantification of CAVC valves on the basis of 3D echocardiographic images. These methods were applied to model the annulus, leaflets, and papillary muscle (PM) structure of 35 patients (29 with trisomy 21) with CAVC using transthoracic 3D echocardiography. The mean leaflet and annular shapes were calculated and visualized using shape analysis. Metrics of the complete native CAVC valve structure were compared with those of normal mitral valves using the Mann-Whitney U test. Associations between CAVC structure and atrioventricular valve regurgitation were analyzed. RESULTS: CAVC leaflet metrics varied throughout systole. Compared with normal mitral valves, the left CAVC PMs were more acutely angled in relation to the annular plane (P < .001). In addition, the anterolateral PM was laterally and inferiorly rotated in CAVC, while the posteromedial PM was more superiorly and laterally rotated, relative to normal mitral valves (P < .001). Lower native CAVC atrioventricular valve annular height and annular height-to-valve width ratio before repair were both associated with moderate or greater left atrioventricular valve regurgitation after repair (P < .01). CONCLUSIONS: It is feasible to model and quantify 3D CAVC structure using 3D echocardiographic images. The results demonstrate significant variation in CAVC structure across the cohort and differences in annular, leaflet, and PM structure compared with the mitral valve. These tools may be used in future studies to catalyze future research intended to identify structural associations of valve dysfunction and to optimize repair in this vulnerable and complex population.

Dynamic Annular Modeling of the Unrepaired Complete Atrioventricular Canal Annulus.

BACKGROUND: Repair of complete atrioventricular canal (CAVC) is often complicated by atrioventricular valve regurgitation, particularly of the left-sided valve. Understanding the 3-dimensional (3D) structure of the atrioventricular canal annulus before repair may help to inform optimized repair. However, the 3D shape and movement of the CAVC annulus has been neither quantified nor rigorously compared with a normal mitral valve annulus. METHODS: The complete annuli of 43 patients with CAVC were modeled in 4 cardiac phases using transthoracic 3D echocardiograms and custom code. The annular structure was compared with the annuli of 20 normal pediatric mitral valves using 3D metrics and statistical shape analysis (Procrustes analysis). RESULTS: The unrepaired CAVC annulus varied in shape significantly throughout the cardiac cycle. Procrustes analysis visually demonstrated that the average normalized CAVC annular shape is more planar than the normal mitral annulus. Quantitatively, the annular height-to-valve width ratio of the native left CAVC atrioventricular valve was significantly lower than that of a normal mitral valve in all systolic phases (P < .001). CONCLUSIONS: The left half of the CAVC annulus is more planar than that of a normal mitral valve with an annular height-to-valve width ratio similar to dysfunctional mitral valves. Given the known importance of annular shape to mitral valve function, further exploration of the association of 3D structure to valve function in CAVC is warranted.

Melody Valve Fracture Causing Mitral Stenosis: Novel Solution for Transapical Valve-in-Valve.

The use of Melody valves in the mitral position has been introduced in clinical practice. Stent fracture is a recognized complication of Melody valve implantation in the pulmonary position; however, reports in the mitral position are rare. We present the case of an 8-year-old boy in whom complete fracture of the proximal stent struts occurred, causing acute severe mitral stenosis, and in whom urgent hybrid transapical Melody valve implantation in the fractured Melody valve was performed successfully using a novel modified technique. This modification simplified the implantation, led to reduced time of the procedure, and minimized hemodynamic instability.

Virtual reality three-dimensional echocardiographic imaging for planning surgical atrioventricular valve repair.

OBJECTIVES: To investigate how virtual reality (VR) imaging impacts decision-making in atrioventricular valve surgery. METHODS: This was a single-center retrospective study involving 15 children and adolescents, median age 6 years (range, 0.33-16) requiring surgical repair of the atrioventricular valves between the years 2016 and 2019. The patients' preoperative 3-dimesnional (3D) echocardiographic data were used to create 3D visualization in a VR application. Five pediatric cardiothoracic surgeons completed a questionnaire formulated to compare their surgical decisions regarding the cases after reviewing conventionally presented 2-dimesnional and 3D echocardiographic images and again after visualization of 3D echocardiograms using the VR platform. Finally, intraoperative findings were shared with surgeons to confirm assessment of the pathology. RESULTS: In 67% of cases presented with VR, surgeons reported having "more" or "much more" confidence in their understanding of each patient's pathology and their surgical approach. In all but one case, surgeons were at least as confident after reviewing the VR compared with standard imaging. The case where surgeons reported to be least confident on VR had the worst technical quality of data used. After viewing patient cases on VR, surgeons reported that they would have made minor modifications to surgical approach in 53% and major modifications in 7% of cases. CONCLUSIONS: The main impact of viewing imaging on VR is the improved clarity of the anatomical structures. Surgeons reported that this would have impacted the surgical approach in the majority of cases. Poor-quality 3D echocardiographic data were associated with a negative impact of VR visualization; thus. quality assessment of imaging is necessary before projecting in a VR format.

A Virtual Reality System for Improved Image-Based Planning of Complex Cardiac Procedures.

The intricate nature of congenital heart disease requires understanding of the complex, patient-specific three-dimensional dynamic anatomy of the heart, from imaging data such as three-dimensional echocardiography for successful outcomes from surgical and interventional procedures. Conventional clinical systems use flat screens, and therefore, display remains two-dimensional, which undermines the full understanding of the three-dimensional dynamic data. Additionally, the control of three-dimensional visualisation with two-dimensional tools is often difficult, so used only by imaging specialists. In this paper, we describe a virtual reality system for immersive surgery planning using dynamic three-dimensional echocardiography, which enables fast prototyping for visualisation such as volume rendering, multiplanar reformatting, flow visualisation and advanced interaction such as three-dimensional cropping, windowing, measurement, haptic feedback, automatic image orientation and multiuser interactions. The available features were evaluated by imaging and nonimaging clinicians, showing that the virtual reality system can help improve the understanding and communication of three-dimensional echocardiography imaging and potentially benefit congenital heart disease treatment.

Multimodality cardiac evaluation in children and young adults with multisystem inflammation associated with COVID-19.

AIMS: Following the peak of the UK COVID-19 epidemic, a new multisystem inflammatory condition with significant cardiovascular effects emerged in young people. We utilized multimodality imaging to provide a detailed sequential description of the cardiac involvement. METHODS AND RESULTS: Twenty consecutive patients (mean age 10.6 ± 3.8 years) presenting to our institution underwent serial echocardiographic evaluation on admission (median day 5 of illness), the day coinciding with worst cardiac function (median day 7), and the day of discharge (median day 15). We performed cardiac computed tomography (CT) to assess coronary anatomy (median day 15) and cardiac magnetic resonance imaging (CMR) to assess dysfunction (median day 20). On admission, almost all patients displayed abnormal strain and tissue Doppler indices. Three-dimensional (3D) echocardiographic ejection fraction (EF) was <55% in half of the patients. Valvular regurgitation (75%) and small pericardial effusions (10%) were detected. Serial echocardiography demonstrated that the mean 3D EF deteriorated (54.7 ± 8.3% vs. 46.4 ± 8.6%, P = 0.017) before improving at discharge (P = 0.008). Left main coronary artery (LMCA) dimensions were significantly larger at discharge than at admission (Z score -0.11 ± 0.87 vs. 0.78 ± 1.23, P = 0.007). CT showed uniform coronary artery dilatation commonly affecting the LMCA (9/12). CMR detected abnormal strain in all patients with global dysfunction (EF <55%) in 35%, myocardial oedema in 50%, and subendocardial infarct in 5% (1/20) patients. CONCLUSIONS: Pancarditis with cardiac dysfunction is common and associated with myocardial oedema. Patients require close monitoring due to coronary artery dilatation and the risk of thrombotic myocardial infarction.

Transcatheter Correction of Superior Sinus Venosus Atrial Septal Defects as an Alternative to Surgical Treatment.

BACKGROUND: The superior sinus venosus atrial septal defect (SVASD) is characterized by deficiency of the common wall between the superior vena cava (SVC) and the right upper pulmonary vein (RUPV), which is no longer committed to the left atrium. OBJECTIVES: This study sought to evaluate the potential for redirecting the SVC and RUPV flow to the right and left atria, respectively, by implantation of a covered stent in the SVC. METHODS: Review of 48 consecutive adult SVASD patients undergoing assessment for correction. Pre-procedural evaluation included cross-sectional imaging and ex vivo simulation using printed or virtual 3-dimensional models. RESULTS: Transcatheter correction was performed in 25 patients, with a further 6 awaiting stent implantation. Only 8 patients were deemed technically unsuitable. The procedure involved balloon test inflation in the anticipated stent landing zone with simultaneous transesophageal echocardiography and pulmonary venography to confirm defect closure and unobstructed pulmonary venous drainage, followed by deployment of a 10-zig covered Cheatham platinum stent. Stents of lengths between 5 and 8 cm were implanted. A second, uncovered stent was used for anchoring in 9 patients. The RUPV was protected with a high-pressure balloon during stent implantation to prevent pulmonary venous obstruction in 4 patients. The median follow-up period was 1.4 (interquartile range: 0.8 to 1.7) years, with no mortality. Stent embolization occurred in 1 patient; another required drainage of hemopericardium. Cardiac computed tomography after 3 months confirmed unobstructed pulmonary venous return. At latest follow-up, a residual shunt was present in 1 patient. CONCLUSIONS: Transcatheter correction of SVASD may be considered as an alternative to surgery in a substantial proportion of patients.

Cardiac expression of Brn-3a and Brn-3b POU transcription factors and regulation of Hsp27 gene expression.

The Brn-3 family of transcription factors play a critical role in regulating expression of genes that control cell fate, including the small heat shock protein Hsp27. The aim of this study was to investigate the relationship between Brn-3a and Brn-3b and Hsp27 expression in the developing rodent heart. Brn-3a and Brn-3b were detected from embryonic days 9.5-10.5 (E9.5-E10.5) in the mouse heart, with significant increases seen later during development. Two isoforms (long and short) of each protein were detected during embryogenesis and postnatally. Brn-3a messenger RNA (mRNA) and protein were localized by E13.0 to the atrio-ventricular (AV) valve cushions and leaflets, outflow tract (OFT), epicardium and cardiac ganglia. By E14.5, Brn-3a was also localised to the septa and compact ventricular myocardium. An increase in expression of the long Brn-3a(l) isoform between E17 and adult coincided with a decrease in expression of Brn-3b(l) and a marked increase in expression of Hsp27. Hearts from Brn-3a-/- mice displayed a partially penetrant phenotype marked by thickening of the endocardial cushions and AV valve leaflets and hypoplastic ventricular myocardium. Loss of Brn-3a was correlated with a compensatory increase in Brn-3b and GATA3 mRNA but no change in Hsp27 mRNA. Reporter assays in isolated cardiomyocytes demonstrated that both Brn-3a and Brn-3b activate the hsp27 promoter via a consensus Brn-3-binding site. Therefore, Brn-3 POU factors may play an important role in the development and maintenance of critical cell types and structures within the heart, in part via developmental regulation of myocardial Hsp27 expression. Furthermore, Brn-3a may be necessary for correct valve and myocardial remodelling and maturation.

Expression of the Brn-3b transcription factor correlates with expression of HSP-27 in breast cancer biopsies and is required for maximal activation of the HSP-27 promoter.

In breast cancer, overexpression of the small heat shock protein, HSP-27, is associated with increased anchorage-independent growth, increased invasiveness, and resistance to chemotherapeutic drugs and is associated with poor prognosis and reduced disease-free survival. Therefore, factors that increase the expression of HSP-27 in breast cancer are likely to affect the prognosis and outcome of treatment. In this study, we show a strong correlation between elevated levels of the Brn-3b POU transcription factor and high levels of HSP-27 protein in manipulated MCF-7 breast cancer cells as well as in human breast biopsies. Conversely, HSP-27 is decreased on loss of Brn-3b. In cotransfection assays, Brn-3b can strongly transactivate the HSP-27 promoter, supporting a role for direct regulation of HSP-27 expression. Brn-3b also cooperates with the estrogen receptor (ER) to facilitate maximal stimulation of the HSP-27 promoter, with significantly enhanced activity of this promoter observed on coexpression of Brn-3b and ER compared with either alone. RNA interference and site-directed mutagenesis support the requirement for the Brn-3b binding site on the HSP-27 promoter, which facilitates maximal transactivation either alone or on interaction with the ER. Chromatin immunoprecipitation provides evidence for association of Brn-3b with the HSP-27 promoter in the intact cell. Thus, Brn-3b can, directly and indirectly (via interaction with the ER), activate HSP-27 expression, and this may represent one mechanism by which Brn-3b mediates its effects in breast cancer cells.

Detection of heart disease by open access echocardiography: a retrospective analysis of general practice referrals.

BACKGROUND: Heart disease is difficult to detect clinically and it has been suggested that echocardiography should be available to all patients with possible cardiac symptoms or signs. AIM: To analyse the results of 2 years of open access echocardiography for the frequency of structural heart disease according to request. DESIGN AND SETTING: Retrospective database analysis in a teaching hospital open access echocardiography service. METHOD: Reports of all open access transthoracic echocardiograms between January 2011 and December 2012 were categorised as normal, having minor abnormalities, or significant abnormalities according to the indication. RESULTS: There were 2343 open access echocardiograms performed and there were significant abnormalities in 29%, predominantly valve disease (n = 304, 13%), LV systolic dysfunction (n = 179, 8%), aortic dilatation (n = 80, 3%), or pulmonary hypertension (n = 91, 4%). If echocardiography had been targeted at a high-risk group, 267 with valve disease would have been detected (compared to 127 with murmur alone) and 139 with LV systolic dysfunction (compared to 91 with suspected heart failure alone). Most GP practices requested fewer than 10 studies, but 6 practices requested over 70 studies. CONCLUSION: Open access echocardiograms are often abnormal but structural disease may not be suspected from the clinical request. Uptake by individual practices is patchy. A targeted expansion of echocardiography in patients with a high likelihood of disease is therefore likely to increase the detection of clinically important pathology.

A training programme in screening echocardiography.

BACKGROUND: Although the value of echocardiography in acutely unwell patients is well established, it is often difficult to deliver conventional studies immediately. This has led to the development of training programmes in screening echocardiography. CONTEXT: Echocardiography is a difficult skill to master and requires an integration of knowledge-based learning and mentored practical training. INNOVATION: We developed a three-stage programme: (1) a 1-day course containing didactic lectures on normal and abnormal pathology, a 2-hour practical element with rotation through different tutors then seminars and self-assessment, with an interactive quiz; (2) a period of consolidation via apprenticeship with a recognised trainer; and (3) formal assessment. IMPLICATIONS: We propose a specific training programme to teach the difficult practical skill of screening echocardiography. The use of theoretical and practical elements with structured teaching and an apprenticeship may serve as a model for teaching other practical skills in clinical medicine.

Intracardiac malignant Triton tumor: a first presentation.

We present the first case of an intracardiac malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (malignant Triton tumor) in a 63-year-old man who underwent elective, uncomplicated resection of his symptomatic left atrial mass.