Characterization of the Rate of Aortic Dilation in Young Patients with Thoracic Aortic Aneurysm.

Longitudinal changes in aortic diameters of young patients with thoracic aortic aneurysm (TAA) have not been completely described, particularly over long periods of follow-up. This retrospective study sought to characterize the rates of proximal aortic dilation in young patients, identify risk factors for TAA progression, and evaluate the predictive utility of early echocardiographic follow-up. Inclusion criteria were: (1) TAA or TAA-predisposing genetic diagnosis, (2) age < 25 years at first echocardiogram, and (3) minimum of 5 years of echocardiographic follow-up. Proximal aortic diameters were measured by echocardiography and Z-scores calculated to index for body surface area. TAA severity was classified as no TAA (Z-score < 2), mild (Z-score 2 to 4), or at least moderate (Z-score > 4). Among 141 included patients, mean age at first echocardiogram was 7.3 ± 3.5 years. Mean follow-up duration was 9.8 ± 3.5 years. Fifty five patients had a genetic syndrome, and 38 of the non-syndromic patients had bicuspid aortic valve (BAV). The rate of aortic dilation was significantly higher at the ascending aorta than other aortic segments. BAV and age > 10 years at first echocardiogram were associated with increased rate of ascending aorta dilation. At the ascending aorta, over 25% of patients had categorical increase in TAA severity between first and last echocardiograms, and such patients demonstrated higher rate of dilation within their first 2 years of follow-up. These longitudinal findings highlight progressive ascending aorta dilation in young patients, which may worsen around adolescence. This may help determine timing of follow-up and target ages for clinical trials.

Improved outcomes in neonates who require venoarterial extracorporeal membrane oxygenation after the Norwood procedure.

BACKGROUND: Extracorporeal membrane oxygenation after the Norwood procedure has historically been associated with poor outcomes, with reported hospital survival rates of 13%-48%. We hypothesized that contemporary outcomes in this population have improved. We aimed to compare clinical outcomes of contemporary cohorts of patients with functional single ventricle physiology who did and did not receive extracorporeal membrane oxygenation after the Norwood procedure. METHODS: Single-center retrospective cohort study of patients with single ventricle anatomy who underwent the Norwood procedure between 2009 and 2017 was performed. Kaplan-Meier survival curves were constructed, and Cox proportional hazard regression analyses were performed to compare transplant-free survival in patients who did and did not receive venoarterial extracorporeal membrane oxygenation. RESULTS: In total, 85 patients met inclusion criteria. Venoarterial extracorporeal membrane oxygenation was utilized in 25 patients (29%). A total of 18 patients (72%) who received venoarterial extracorporeal membrane oxygenation survived to hospital discharge, compared to 54 patients (92%) who did not receive venoarterial extracorporeal membrane oxygenation (p = 0.013). Post-discharge transplant-free survival was not significantly different between patients who did and did not receive venoarterial extracorporeal membrane oxygenation (log-rank p value = 0.28). Cox proportional hazard regression analysis revealed that the occurrence of cardiac arrest requiring cardiopulmonary resuscitation (hazard ratio = 4.5; 95% confidence interval = 2.0-10.1) during the perioperative period was independently associated with death or transplantation, whereas venoarterial extracorporeal membrane oxygenation was not an independent risk factor for death or transplantation (hazard ratio = 2.0; 95% confidence interval = 0.8-4.9). CONCLUSION: In our cohort of children who received venoarterial extracorporeal membrane oxygenation after the Norwood procedure, hospital survival was improved compared to historical data. In addition, venoarterial extracorporeal membrane oxygenation utilization was not independently associated with worse outcomes.

The Risk of Thromboembolic Complications in Fontan Patients with Atrial Flutter/Fibrillation Treated with Electrical Cardioversion.

Atrial flutter or fibrillation (AFF) remains a major chronic complication of the Fontan procedure. This complication further predisposes this patient population to thromboembolic events. However, the incidence of thromboembolic complications in Fontan patients with AFF prior to or acutely after electrical cardioversion is unknown. This study aimed to characterize the risk of post-cardioversion thromboembolic events in this population. We performed a retrospective medical record review of all patients with a history of Fontan operation treated with direct current cardioversion for AFF at Riley Children's Hospital between June 1992 and March 2014. A total of 57 patients were identified and reviewed. A total of 216 episodes of AFF required electrical cardioversion. Patients were treated with anticoagulation/antiplatelet therapy in 86.1 % (N = 186) of AFF episodes. Right atrial or Fontan conduit clots were observed in 33 patients (57.9 %) with 61 episodes of AFF. Approximately half (49.2 %, N = 30) of these episodes were treated immediately with electrical cardioversion. Twenty-five of 33 (75.8 %) patients with intracardiac thrombi had an atriopulmonary Fontan. Five (15.2 %) patients with a lateral caval tunnel had clots in the Fontan conduit, and three (9.1 %) patients with right atrium to right ventricular outflow tract (RVOT) connections presented with right atrial mural thrombi. Nine of the 57 (15.8 %) patients had documented stroke, and three (5.3 %) patients had pulmonary emboli during follow-up, although none of these emboli were associated with electrical cardioversion. The risk of thrombus and thromboembolism associated with AFF is high in the Fontan population. However, the risk of thromboembolism associated with cardioversion in the setting of anticoagulation is very low.

Midterm survival of infants requiring postoperative extracorporeal membrane oxygenation after Norwood palliation.

This study reports the mid-term survival for neonates undergoing extracorporeal membrane oxygenation (ECMO) after Norwood palliation at a single center. Limited data exist on the mid-term survival of patients undergoing ECMO after Norwood palliation. We reviewed our ECMO experience from July 1994 to October 2008 and compared two groups: patients who required ECMO after Norwood palliation and patients who underwent Norwood palliation without ECMO. We analyzed 30-day survival, survival to hospital discharge, and survival to most recent follow-up. One hundred sixty patients underwent Norwood palliation for hypoplastic left heart syndrome (HLHS) and its variants. A total of 32 patients (20%) required postoperative ECMO. Using Kaplan-Meier analysis, the predicted survival rates for Norwood/non-ECMO patients to 30 days, 1 year, and 3 years after the procedure are 87.6% (CI 79.5-91.5%), 62.5% (CI 54.3-71.0%), and 59.9% (CI 50.8-67.8%), respectively. Survival to 30 days, 1 year, and 3 years after Norwood was significantly decreased in Norwood/ ECMO patients, with predicted survival rates of 50.0% (CI 31.9-65.7%), 24.6% (CI 11.4-40.4), and 13.2% (CI 3.9-28.3%), respectively (p < 0.0001). Risk factors for hospital mortality included nonelective or emergency placement onto ECMO, longer duration of ECMO support, and the development of acute renal failure while on ECMO. Of the original Norwood/ECMO hospital survivors, only half of these patients survived a mean of nearly 4 years. ECMO after Norwood palliation is associated with significant mortality. Our data suggest that neonates who require ECMO after Norwood palliation are prone to continued attrition once discharged from the hospital.

Comparison between transthoracic echocardiography and cardiac magnetic resonance imaging in patients status post atrial switch procedure.

OBJECTIVES: This study compares image quality, cost, right ventricular ejection fraction analysis, and baffle visualization between transthoracic echocardiography and cardiac magnetic resonance imaging in those status post atrial switch for transposition of the great arteries. BACKGROUND: This population requires imaging for serial evaluations. Transthoracic echocardiography is often first line but has drawbacks, many of which are addressed by cardiac magnetic resonance imaging. METHODS: Twelve patients (mean age 25 years) with relatively concurrent (mean 157 days) studies were included. Three separate echocardiography and magnetic resonance imaging physicians independently analyzed baffles, image quality, and right ventricular ejection fractions. Institutional and Medicaid charges were compared. RESULTS: For right ventricular ejection fraction, echocardiography (36.1%) underestimated cardiac magnetic resonance imaging (47.8%, P = .002). Image quality for transthoracic echocardiography was significantly rated lower than cardiac magnetic resonance imaging (P = .002). Baffles were better seen in cardiac magnetic resonance imaging (transthoracic echocardiography vs. cardiac magnetic resonance imaging: superior vena cava 86% vs. 100% [P = .063]; inferior vena cava 33% vs. 97% [P = .002]; pulmonary vein 92% vs. 100% [P = .250]). Comparing hospital charges and Medicaid reimbursement, transthoracic echocardiography respectively costs 18% and 38% less than cardiac magnetic resonance imaging. CONCLUSIONS: In conclusion, transthoracic echocardiography underestimated right ventricular ejection fraction compared to cardiac magnetic resonance imaging. Cardiac magnetic resonance imaging had consistently higher image quality and better visualization of the baffles. Cost differences are minimal. We propose that cardiac magnetic resonance imaging be considered first line for imaging in certain patients' status post atrial switch procedure.

Crystal structure of the Pseudomonas aeruginosa virulence factor regulator.

Virulence factor regulator (Vfr) enhances Pseudomonas aeruginosa pathogenicity through its role as a global transcriptional regulator. The crystal structure of Vfr shows that it is a winged-helix DNA-binding protein like its homologue cyclic AMP receptor protein (CRP). In addition to an expected primary cyclic AMP-binding site, a second ligand-binding site is nestled between the N-terminal domain and the C-terminal helix-turn-helix domain. Unlike CRP, Vfr is a symmetric dimer in the absence of DNA. Removal of seven disordered N-terminal residues of Vfr prevents the growth of P. aeruginosa.

Attempts to change culture in a line-obsessed pediatric world: the Riley Heart Center line initiative.

Interventions to reduce central line-associated bloodstream infections in pediatric patients have not yet been validated. Unique approaches to reducing infection rates may be warranted in this population.

A review of atypical antipsychotic medications for posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can be a chronic and disabling illness with a limited response to antidepressant treatment, particularly in the case of combat-induced PTSD. The purpose of this study is to review randomized controlled and open-label trials of atypical antipsychotics for the treatment of PTSD. We conducted PUBMED and PILOTS database searches for clinical trials of atypical antipsychotic medications for PTSD in May 2010. Eighteen clinical trials (10 double-blind placebo-controlled, eight open-label) of atypical antipsychotics for PTSD were found and reviewed. Effect sizes of double-blind placebo-controlled trials were small, but were positive for risperidone and quetiapine. Intrusive and hypervigilance symptom subscales showed the most improvement. We concluded that atypical antipsychotic medications have a modest benefit for the treatment of PTSD. Larger randomized controlled trials are needed to clarify the potential utility of these medications in the treatment of PTSD and more rigorous examination of metabolic side effects is warranted.

Is left ventricular noncompaction in children truly an isolated lesion?

Left ventricular noncompaction (LVNC) is a form of cardiomyopathy resulting from a disorder of endomyocardial morphogenesis. It has been associated with significant morbidity and mortality. The aim of this study was to characterize associated cardiac findings in children with LVNC and to identify risk factors associated with increased mortality. From our echocardiography database, we identified 46 patients diagnosed with LVNC between December 1999 and February 2005. The mean age at presentation was 3.6 +/- 5.6 years, and the mean duration of follow-up was 1.9 +/- 2.1 years. Left ventricular ejection fraction was decreased in 24 patients (52%; mean 39.5% +/- 13.1%). Thirty-six patients (78%) had associated cardiac lesions, including atrial septal defect (n = 16 [35%]), ventricular septal defect (n = 17 [37%]), patent ductus arteriosus (n = 14 [30%]), and Ebstein's anomaly (n = 5 [11%]). Electrocardiogram abnormalities were found in 80% of patients; most commonly they included left (n = 15 [43%]) and right ventricular hypertrophy (n = 19 [54%]). Documented arrhythmias included ectopic atrial rhythm (n = 2), junctional rhythm (n = 2), supraventricular tachycardia (n = 2), and ventricular tachycardia (n = 1). Overall mortality was 20%, and there was no association with ejection fraction, morphologic defect, or arrhythmia. Mean age at diagnosis in survivors (4.5 +/- 6.1 years) was higher than nonsurvivors (0.4 +/- 0.7 years) (p < 0.0001). LVNC is a rarely isolated form of cardiomyopathy, and it is associated with significant additional cardiac abnormalities. Although it does not have an invariably fatal course, early presentation in infancy does carry an increased risk of mortality.

Tonal interface to MacroMolecules (TIMMol): A textual and tonal tool for molecular visualization.

We developed the three-dimensional visualization software, Tonal Interface to MacroMolecules or TIMMol, for studying atomic coordinates of protein structures. Key features include audio tones indicating x, y, z location, identification of the cursor location in one-dimensional and three-dimensional space, textual output that can be easily linked to speech or Braille output, and the ability to scroll along the main chain backbone of a protein structure. This program was initially designed for visually impaired users, and it already has shown its effectiveness in helping a blind researcher study X-ray crystal structure data. Subsequently, TIMMol has been enhanced with a graphical display to act as a bridge to ease communication between sighted and visually impaired users as well as to serve users with spatial visualization difficulties. We performed a pilot study to assess the efficacy of the program in conveying three-dimensional information about proteins with and without graphical output to a general scientific audience. Attitudes regarding using TIMMol were assessed using Rasmol, a common visualization package, for comparison. With the use of text and tones exclusively, a majority of users were able to identify specific secondary structure elements, three-dimensional relationships among atoms, and atoms coordinating a ligand. In addition, a majority of users saw benefits in using TIMMol and would recommend it to those having difficulty with standard tools.