T1 mapping of the myocardium and liver in the single ventricle population.

BACKGROUND: Fontan associated liver disease (FALD) is an increasingly recognized complication of the single ventricle circulation characterized by hepatic venous congestion leading to hepatic fibrosis. Within the Fontan myocardium, fibrotic myocardial remodeling may occur and lead to ventricular dysfunction. Magnetic resonance imaging (MRI) T1 mapping can characterize both myocardial and liver properties. OBJECTIVE: The aim of this study was to compare myocardial and liver T1 between single ventricle patients with and without a Fontan and biventricular controls. MATERIALS AND METHODS: A retrospective study of 3 groups of patients: 16 single ventricle patients before Fontan (SVpre 2 newborns, 9 pre-Glenn, 5 pre-Fontan, 31% single right ventricle [SRV]), 16 Fontans (56% SRV) and 10 repaired d-transposition of the great arteries (TGA). Native modified Look-Locker inversion T1 times were measured in the myocardium and liver. Cardiac MRI parameters, myocardial and liver T1 values were compared in the three groups. Correlations were assessed between liver T1 and cardiac parameters. RESULTS: Myocardial T1 was higher in SVpre (1,056 ± 48 ms) and Fontans (1,047 ± 41 ms) compared to TGA (1,012 ± 48 ms, P < 0.05). Increased liver T1 was found in both SVpre (683 ± 82 ms) and Fontan (727 ± 49 ms) patients compared to TGA patients (587 ± 58 ms, P < 0.001). There was no difference between single left ventricle (SLV) versus SRV myocardial or liver T1. Liver T1 showed moderate correlations with myocardial T1 (r = 0.48, confidence interval [CI] 0.26-0.72) and ejection fraction (r = -0.36, CI -0.66-0.95) but not with other volumetric parameters. CONCLUSION: Increased liver T1 at both pre- and post-Fontan stages suggests there are intrinsic liver abnormalities early in the course of single ventricle palliation. Increased myocardial T1 and its relationship to liver T1 suggest a combination of edema from passive venous congestion and/or myocardial fibrosis occurring in this population. Liver T1 may provide an earlier marker of liver disease warranting further study.

Speckle-Tracking Analysis in Fetuses With Tetralogy of Fallot: Evaluation of Right and Left Ventricular Contractility and Left Ventricular Function.

OBJECTIVES: This study examines fetuses with tetralogy of Fallot (TOF) and evaluates the right (RV) and left (LV) ventricular contractility and LV function using speckle-tracking analysis of the endocardium. METHODS: The study group consisted of 44 fetuses with TOF, of which 34% had pulmonary valve atresia (N = 15) and 59% (N = 26) had pulmonary valve stenosis. The RV and LV global fractional area change, longitudinal contractility (longitudinal strain, free wall strain, septal strain, free wall and septal annular fractional shortening, and free wall and septal wall annular plane systolic excursion), and transverse contractility (24-segment fractional shortening) as well as LV functional assessment (stroke volume, cardiac output, and ejection fraction) were measured using speckle-tracking analysis. The z-scores of the measurements were compared to 200 controls. RESULTS: Compared to controls, measurements of LV contractility in fetuses with TOF demonstrated significantly abnormal values for global contractility, longitudinal contractility, and transverse contractility of the mid and apical segments. LV function was abnormal for stroke volume (SV), cardiac output (CO), and ejection fraction (EF). In comparison, RV contractility demonstrated no significant difference between TOF and control z-score values for RV global contractility. Only two RV measurements were found to be abnormal: longitudinal contractility and transverse contractility of the apical segments. CONCLUSION: Using multiple measurement tools to evaluate global, longitudinal, and transverse contractility, this study identified significant differences between fetuses with TOF and healthy controls, with greater contractility abnormalities seen in the LV than in the RV.

Evaluation of Fetal Cardiac Size and Shape: A New Screening Tool to Identify Fetuses at Risk for Tetralogy of Fallot.

OBJECTIVE: Prenatal detection rates for tetralogy of Fallot (TOF) vary between 23 and 85.7%, in part because of the absence of significant structural abnormalities of the 4-chamber view (4CV), as well as the relative difficulty in detection of abnormalities during the screening examination of the outflow tracts. The purpose of this study was to evaluate whether the 4CV and ventricles in fetuses with TOF may be characterized by abnormalities of size and shape of these structures. METHODS: This study retrospectively evaluated 44 fetuses with the postnatal diagnosis of TOF. Measurements were made from the 4CV (end-diastolic length, width, area, global sphericity index, and cardiac axis) and the right (RV) and left (LV) ventricles (area, length, 24-segment transverse widths, sphericity index, and RV/LV ratios). Logistic regression analysis was performed to identify variables that might separate fetuses with TOF from normal controls. RESULTS: The mean gestational age at the time of the last examination prior to delivery was 28 weeks 5 days (SD 4 weeks, 4 days). The mean z-scores were significantly lower in fetuses with TOF for the 4CV and RV and LV measurements of size and shape. Logistic regression analysis identified simple linear measurements of the 4CV, RV, and LV that had a sensitivity of 90.9 and specificity of 98.5% that outperformed the 4CV cardiac axis (sensitivity of 22.7%) as a screening tool for TOF. CONCLUSIONS: Measurements of the 4CV, RV, and LV can be used as an adjunct to the outflow tract screening examination to identify fetuses with TOF.

A multicenter survey on post-transplant lymphoproliferative disorders in pediatric heart transplant recipients: A case for development of consensus guidelines for screening, surveillance, and treatment?

Post-transplant lymphoproliferative disorders (PTLD) are the main malignancy seen after pediatric heart transplant and are a significant cause of morbidity and mortality. Prior to the development of detailed guidelines, we sought to identify trends in screening, diagnosis, and treatment of pediatric PTLD. All Pediatric Heart Transplant Society (PHTS) institutions were surveyed. No identifiable patient information was shared. From 56 PHTS centers, 22 responses were received (39.3%). 100% agree PTLD cannot be diagnosed solely based on elevated Epstein-Barr virus (EBV) load. All respondents routinely screen for EBV by blood PCR, but frequency of screening varies. There was intermediate consensus regarding the use of computed tomography (CT) and/or positron emission tomography (PET) in surveillance management for PTLD. Most centers require a diagnostic biopsy before initiating new treatment for PTLD (14 of 18, 77.8%), but many reduce immune suppression based on elevated EBV without pathologic PTLD (16 of 22, 72.7%). Beyond immune modulation, rituximab is most commonly used (9 of 13, 69.2%). Consultation with oncology is common (17 of 17, 100%), but timing varies widely. Our survey highlights significant elements of agreement and significant practice variation among PHTS institutions regarding pediatric PTLD. Reduction of immune suppression prior to pathologic diagnosis of PTLD is a common management strategy. When this fails, rituximab is used, but is most often reserved until after confirmation of the diagnosis. Oncology subspecialists are commonly involved in these cases. Our findings highlight the need to develop improved guidelines for evaluation and treatment of pediatric PTLD.

Transvenous pacemaker implantation after the bidirectional Glenn operation for patients with complex congenital disease.

INTRODUCTION: The bidirectional Glenn operation for congenital heart disease produces anatomical constraints to conventional transvenous pacemaker implantation. An iliac approach, although not previously described in this population, is potentially a preferable alternative to a thoracotomy for epicardial pacing. METHODS AND RESULTS: A single-center retrospective review was performed for all patients that underwent transvenous pacemaker implantation following the bidirectional Glenn operation with partial biventricular repair. Follow-up data, implant indications, and techniques were recorded. Five patients underwent a transvenous iliac approach (median age 26.9 years, interquartile range [IQR] 25.8-27.6). Pacing indications included AV block in 3 patients (2 requiring cardiac resychronization therapy) and sinus node dysfunction in 2. Implanted leads were atrial in 4 and ventricular in 3 (1 of the latter was placed in the coronary sinus). In two cases, transvenous leads were tunneled to a preexisting epicardial abdominal generator. Median follow-up was 4.1 years (range 1.0-16.7 years). One patient underwent device revision for lead position-related groin discomfort; a second patient developed atrial lead failure following a Maze operation and underwent lead replacement by the iliac approach. Patients were not routinely anticoagulated postprocedure given lead position in the subpulmonary circulation. At last follow-up, all patients were alive. One patient underwent heart transplantation 6 months after implant with only partial resolution of pacing-induced cardiomyopathy. CONCLUSIONS: Trans-iliac pacemaker placement may be an effective alternative to surgery for patients requiring permanent pacing after the Glenn operation.

Implementation of Virtual Fontan Heart Camps During a Pandemic.

BACKGROUND: Children with a Fontan operation represent a unique form of congenital heart disease (CHD) that requires multiple cardiac surgeries and procedures with an uncertain long-term outcome. Given the rarity of the types of CHD that require this procedure, many children with a Fontan do not know any others like them. METHODS: With the cancelation of medically supervised heart camps due to the COVID-19 pandemic, we have organized several physician-led virtual day camps for children with a Fontan operation to connect with others in their province and across Canada. The aim of this study was to describe the implementation and evaluation of these camps via the use of an anonymous online survey immediately after the event and reminders on days 2 and 4 postevent. RESULTS: Fifty-one children have participated in at least 1 of our camps. Registration data showed that 70% of participants did not know anyone else with a Fontan. Postcamp evaluations showed that 86% to 94% learned something new about their heart and 95% to 100% felt more connected to other children like them. CONCLUSION: We have demonstrated the implementation of a virtual heart camp to expand the support network for children with a Fontan. These experiences may help to promote healthy psychosocial adjustments through inclusion and relatedness.

Stereoscopic Display Is Superior to Conventional Display for Three-Dimensional Echocardiography of Congenital Heart Anatomy.

BACKGROUND: Three-dimensional echocardiography (3DE) improves visualization of cardiac lesions. Current viewing of 3DE studies on a conventional display diminishes the encoded stereoscopic (stereo) information for depth perception. This study aims to evaluate clinician subjective and objective experience of stereo display compared with nonstereo display of 3DE in congenital heart disease. METHODS: In this prospective study, 22 cardiologists, advanced cardiology trainees, and cardiothoracic surgeons used a commercially available stereo display system with proprietary software to view 10 3DE data sets, alternating between simple and complex lesions. In part A, participants viewed each data set, randomized to 1 minute of stereo display followed by 1 minute of nonstereo display, or vice versa. In part B, participants could freely toggle between stereo and nonstereo display for an additional 90 seconds per data set. Participants answered a series of questions and rated their subjective experience using stereo versus nonstereo display mode on a Likert scale. Objective data on time spent in each display mode during part B and duration of interaction and degree of movement of the 3DE data set in parts A and B were also collected. RESULTS: All clinician groups found stereo display preferable to nonstereo display of 3DE (P < .0001). Viewing complex lesions was rated lower than simple lesions when using nonstereo display (P < .01). Simple and complex lesions were equally well rated when using stereo display (P = .14). When given a choice of display modes in part B, participants spent more time in stereo display (P < .0001) and interacted more with the 3DE data sets in stereo display (P < .0001). CONCLUSIONS: Interactive stereoscopic display of 3DE was preferred over conventional nonstereo display by all clinician groups for viewing both simple and complex lesions. This preference is especially true for viewing complex lesions.

Screening for rejection in symptomatic pediatric heart transplant recipients: the sensitivity of BNP.

As the pediatric OHT population expands, there is increasing demand for convenient, yet sensitive screening techniques to identify children with acute rejection when they present to acute care facilities. In children, symptoms of acute rejection or other causes of graft dysfunction are often non-specific and can mimic other childhood illnesses. The aim of this study was to assess the utility of BNP as a biomarker to assist providers in clinical decision-making when evaluating symptomatic pediatric heart transplant patients. One hundred twenty-two urgent care and emergency room visits from 53 symptomatic pediatric OHT patients were retrospectively reviewed to evaluate the relationship between BNP levels, symptoms, and clinical diagnosis at these visits. An ROC curve was generated to determine the accuracy of BNP as a screening tool for acute rejection in this patient population. In this group of patients, a BNP value of >700 pg/mL was 100% sensitive and 92% specific for detecting allograft acute rejection (NPV of 100%). We concluded that BNP is a highly sensitive screening test for acute rejection in symptomatic pediatric heart transplant patients.

Pediatric cardiomyopathies: causes, epidemiology, clinical course, preventive strategies and therapies.

Pediatric cardiomyopathies, which are rare but serious disorders of the muscles of the heart, affect at least one in every 100,000 children in the USA. Approximately 40% of children with symptomatic cardiomyopathy undergo heart transplantation or die from cardiac complications within 2 years. However, a significant number of children suffering from cardiomyopathy are surviving into adulthood, making it an important chronic illness for both pediatric and adult clinicians to understand. The natural history, risk factors, prevalence and incidence of this pediatric condition were not fully understood before the 1990s. Questions regarding optimal diagnostic, prognostic and treatment methods remain. Children require long-term follow-up into adulthood in order to identify the factors associated with best clinical practice including diagnostic approaches, as well as optimal treatment approaches. In this article, we comprehensively review current research on various presentations of this disease, along with current knowledge about their causes, treatments and clinical outcomes.

Cardiotoxicity in childhood cancer survivors: strategies for prevention and management.

Advances in cancer treatment have greatly improved survival rates of children with cancer. However, these same chemotherapeutic or radiologic treatments may result in long-term health consequences. Anthracyclines, chemotherapeutic drugs commonly used to treat children with cancer, are known to be cardiotoxic, but the mechanism by which they induce cardiac damage is still not fully understood. A higher cumulative anthracycline dose and a younger age of diagnosis are only a few of the many risk factors that identify the children at increased risk of developing cardiotoxicity. While cardiotoxicity can develop at anytime, starting from treatment initiation and well into adulthood, identifying the best cardioprotective measures to minimize the long-term damage caused by anthracyclines in children is imperative. Dexrazoxane is the only known agent to date, that is associated with less cardiac dysfunction, without reducing the oncologic efficacy of the anthracycline doxorubicin in children. Given the serious long-term health consequences of cancer treatments on survivors of childhood cancers, it is essential to investigate new approaches to improving the safety of cancer treatments.

The p-type ATPase superfamily.

P-type ATPases function to provide homeostasis in higher eukaryotes, but they are essentially ubiquitous, being found in all domains of life. Thever and Saier [J Memb Biol 2009;229:115-130] recently reported analyses of eukaryotic P-type ATPases, dividing them into nine functionally characterized and 13 functionally uncharacterized (FUPA) families. In this report, we analyze P-type ATPases in all major prokaryotic phyla for which complete genome sequence data are available, and we compare the results with those for eukaryotic P-type ATPases. Topological type I (heavy metal) P-type ATPases predominate in prokaryotes (approx. tenfold) while type II ATPases (specific for Na(+),K(+), H(+) Ca(2+), Mg(2+) and phospholipids) predominate in eukaryotes (approx. twofold). Many P-type ATPase families are found exclusively in prokaryotes (e.g. Kdp-type K(+) uptake ATPases (type III) and all ten prokaryotic FUPA familes), while others are restricted to eukaryotes (e.g. phospholipid flippases and all 13 eukaryotic FUPA families). Horizontal gene transfer has occurred frequently among bacteria and archaea, which have similar distributions of these enzymes, but rarely between most eukaryotic kingdoms, and even more rarely between eukaryotes and prokaryotes. In some bacterial phyla (e.g. Bacteroidetes, Flavobacteria and Fusobacteria), ATPase gene gain and loss as well as horizontal transfer occurred seldom in contrast to most other bacterial phyla. Some families (i.e. Kdp-type ATPases) underwent far less horizontal gene transfer than other prokaryotic families, possibly due to their multisubunit characteristics. Functional motifs are better conserved across family lines than across organismal lines, and these motifs can be family specific, facilitating functional predictions. In some cases, gene fusion events created P-type ATPases covalently linked to regulatory catalytic enzymes. In one family (FUPA Family 24), a type I ATPase gene (N-terminal) is fused to a type II ATPase gene (C-terminal) with retention of function only for the latter. Several pseudogene-encoded nonfunctional ATPases were identified. Genome minimalization led to preferential loss of P-type ATPase genes. We suggest that in prokaryotes and some unicellular eukaryotes, the primary function of P-type ATPases is protection from extreme environmental stress conditions. The classification of P-type ATPases of unknown function into phylogenetic families provides guides for future molecular biological studies.