Fick versus flow: a real-time invasive cardiovascular magnetic resonance (iCMR) reproducibility study.

BACKGROUND: Cardiac catheterization and cardiovascular magnetic resonance (CMR) imaging have distinct diagnostic roles in the congenital heart disease (CHD) population. Invasive CMR (iCMR) allows for a more thorough assessment of cardiac hemodynamics at the same time under the same conditions. It is assumed but not proven that iCMR gives an incremental value by providing more accurate flow quantification. METHODS: Subjects with CHD underwent real-time 1.5 T iCMR using a passive catheter tracking technique with partial saturation pulse of 40° to visualize the gadolinium-filled balloon, CMR-conditional guidewire, and cardiac structures simultaneously to aid in completion of right (RHC) and left heart catheterization (LHC). Repeat iCMR and catheterization measurements were performed to compare reliability by the Pearson (PCC) and concordance correlation coefficients (CCC). RESULTS: Thirty CHD (20 single ventricle and 10 bi-ventricular) subjects with a median age and weight of 8.3 years (2-33) and 27.7 kg (9.2-80), respectively,  successfully underwent iCMR RHC and LHC. No catheter related complications were encountered. Time taken for first pass RHC and LHC/aortic pull back was 5.1, and 2.9 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 321/328 (98%). One patient with multiple shunts was an outlier and excluded from further analysis. The PCC for catheter-derived pulmonary blood flow (Qp) (0.89, p < 0.001) is slightly lower than iCMR-derived Qp (0.96, p < 0.001), whereas catheter-derived systemic blood flow (Qs) (0.62, p = < 0.001) was considerably lower than iCMR-derived Qs (0.94, p < 0.001). CCC agreement for Qp at baseline (C1-CCC = 0.65, 95% CI 0.41-0.81) and retested conditions (C2-CCC = 0.78, 95% CI 0.58-0.89) were better than for Qs at baseline (C1-CCC = 0.22, 95% CI - 0.15-0.53) and retested conditions (C2-CCC = 0.52, 95% CI 0.17-0.76). CONCLUSION: This study further validates hemodynamic measurements obtained via iCMR. iCMR-derived flows have considerably higher test-retest reliability for Qs. iCMR evaluations allow for more reproducible hemodynamic assessments in the CHD population.

Feasibility and safety of quantitative adenosine stress perfusion cardiac magnetic resonance imaging in pediatric heart transplant patients with and without coronary allograft vasculopathy.

BACKGROUND: Pediatric heart transplant patients require cardiac catheterization to monitor for coronary allograft vasculopathy. Cardiac catheterization has no safe and consistent method for measuring microvascular disease. Stress perfusion cardiac magnetic resonance imaging (MRI) assessing microvascular disease has been performed in adults. OBJECTIVE: To investigate the feasibility and safety of performing cardiac MRI with quantitative adenosine stress perfusion testing in pediatric heart transplant patients with and without coronary allograft vasculopathy. MATERIALS AND METHODS: All pediatric heart transplant patients with coronary vasculopathy at our institution were asked to participate. Age- and gender-matched pediatric heart transplant patients without vasculopathy were recruited for comparison. Patients underwent cardiac MRI with adenosine stress perfusion testing. RESULTS: Sixteen pediatric heart transplant patients, ages 6-22 years, underwent testing. Nine patients had vasculopathy by angiography. No heart block or other complications occurred during the study. The myocardial perfusion reserve for patients with vasculopathy showed no significant difference with comparison patients (median: 1.43 vs. 1.48; P=0.49). Values for both groups were lower than expected values based on previous adult studies. The patients were also analyzed for time after transplant and the number of rejection episodes. Patients within 6 years of transplantation had a nonsignificant trend toward a higher myocardial perfusion reserve (median: 1.57) versus patients with older transplants (median: 1.47; P=0.46). Intra- and interobserver reproducibility were 97% and 92%, respectively. CONCLUSION: Myocardial perfusion reserve is a safe and feasible method for estimating myocardial perfusion in pediatric heart transplant patients. There is no reliable way to monitor microvascular disease in pediatric patients. This method shows potential and deserves investigation in a larger cohort.

Lymphatic pathway evaluation in congenital heart disease using 3D whole-heart balanced steady state free precession and T2-weighted cardiovascular magnetic resonance.

BACKGROUND: Due to passive blood flow in palliated single ventricle, central venous pressure increases chronically, ultimately impeding lymphatic drainage. Early visualization and treatment of these malformations is essential to reduce morbidity and mortality. Cardiovascular magnetic resonance (CMR) T2-weighted lymphangiography (T2w) is used for lymphatic assessment, but its low signal-to-noise ratio may result in incomplete visualization of thoracic duct pathway. 3D-balanced steady state free precession (3D-bSSFP) is commonly used to assess congenital cardiac disease anatomy. Here, we aimed to improve diagnostic imaging of thoracic duct pathway using 3D-bSSFP. METHODS: Patients underwent CMR during single ventricle or central lymphatic system assessment using T2w and 3D-bSSFP. T2w parameters included 3D-turbo spin echo (TSE), TE/TR = 600/2500 ms, resolution = 1 × 1 × 1.8 mm, respiratory triggering with bellows. 3D-bSSFP parameters included electrocardiogram triggering and diaphragm navigator, 1.6 mm isotropic resolution, TE/TR = 1.8/3.6 ms. Thoracic duct was identified independently in T2w and 3D-bSSFP images, tracked completely from cisterna chyli to its drainage site, and classified based on severity of lymphatic abnormalities. RESULTS: Forty-eight patients underwent CMR, 46 of whom were included in the study. Forty-five had congenital heart disease with single ventricle physiology. Median age at CMR was 4.3 year (range 0.9-35.1 year, IQR 2.4 year), and median weight was 14.4 kg (range, 7.9-112.9 kg, IQR 5.2 kg). Single ventricle with right dominant ventricle was noted in 31 patients. Thirty-eight patients (84%) were status post bidirectional Glenn and 7 (16%) were status post Fontan anastomosis. Thoracic duct visualization was achieved in 45 patients by T2w and 3D-bSSFP. Complete tracking to drainage site was attained in 11 patients (24%) by T2w vs 25 (54%) by 3D-bSSFP and in 28 (61%) by both. Classification of lymphatics was performed in 31 patients. CONCLUSION: Thoracic duct pathway can be visualized by 3D-bSSFP combined with T2w lymphangiography. Cardiac triggering and respiratory navigation likely help retain lymphatic signal in the retrocardiac area by 3D-bSSFP. Visualizing lymphatic system leaks is challenging on 3D-bSSFP images alone, but 3D-bSSFP offers good visualization of duct anatomy and landmark structures to help plan interventions. Together, these sequences can define abnormal lymphatic pathway following single ventricle palliative surgery, thus guiding lymphatic interventional procedures.

Retraining Convolutional Neural Networks for Specialized Cardiovascular Imaging Tasks: Lessons from Tetralogy of Fallot.

Ventricular contouring of cardiac magnetic resonance imaging is the gold standard for volumetric analysis for repaired tetralogy of Fallot (rTOF), but can be time-consuming and subject to variability. A convolutional neural network (CNN) ventricular contouring algorithm was developed to generate contours for mostly structural normal hearts. We aimed to improve this algorithm for use in rTOF and propose a more comprehensive method of evaluating algorithm performance. We evaluated the performance of a ventricular contouring CNN, that was trained on mostly structurally normal hearts, on rTOF patients. We then created an updated CNN by adding rTOF training cases and evaluated the new algorithm's performance generating contours for both the left and right ventricles (LV and RV) on new testing data. Algorithm performance was evaluated with spatial metrics (Dice Similarity Coefficient (DSC), Hausdorff distance, and average Hausdorff distance) and volumetric comparisons (e.g., differences in RV volumes). The original Mostly Structurally Normal (MSN) algorithm was better at contouring the LV than the RV in patients with rTOF. After retraining the algorithm, the new MSN + rTOF algorithm showed improvements for LV epicardial and RV endocardial contours on testing data to which it was naïve (N = 30; e.g., DSC 0.883 vs. 0.905 for LV epicardium at end diastole, p < 0.0001) and improvements in RV end-diastolic volumetrics (median %error 8.1 vs 11.4, p = 0.0022). Even with a small number of cases, CNN-based contouring for rTOF can be improved. This work should be extended to other forms of congenital heart disease with more extreme structural abnormalities. Aspects of this work have already been implemented in clinical practice, representing rapid clinical translation. The combined use of both spatial and volumetric comparisons yielded insights into algorithm errors.

Invasive cardiovascular magnetic resonance (iCMR) for diagnostic right and left heart catheterization using an MR-conditional guidewire and passive visualization in congenital heart disease.

BACKGROUND: Today's standard of care, in the congenital heart disease (CHD) population, involves performing cardiac catheterization under x-ray fluoroscopy and cardiac magnetic resonance (CMR) imaging separately. The unique ability of CMR to provide real-time functional imaging in multiple views without ionizing radiation exposure has the potential to be a powerful tool for diagnostic and interventional procedures. Limiting fluoroscopic radiation exposure remains a challenge for pediatric interventional cardiologists. This pilot study's objective is to establish feasibility of right (RHC) and left heart catheterization (LHC) during invasive CMR (iCMR) procedures at our institution in the CHD population. Furthermore, we aim to improve simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures. METHODS: Subjects with CHD were enrolled in a pilot study for iCMR procedures at 1.5 T with an MR-conditional guidewire. The CMR area is located adjacent to a standard catheterization laboratory. Using the interactive scanning mode for real-time control of the imaging location, a dilute gadolinium-filled balloon-tip catheter was used in combination with an MR-conditional guidewire to obtain cardiac saturations and hemodynamics. A recently developed catheter tracking technique using a real-time single-shot balanced steady-state free precession (bSSFP), flip angle (FA) 35-45°, echo time (TE) 1.3 ms, repetition time (TR) 2.7 ms, 40° partial saturation (pSAT) pre-pulse was used to visualize the gadolinium-filled balloon, MR-conditional guidewire, and cardiac structures simultaneously. MR-conditional guidewire visualization was enabled due to susceptibility artifact created by distal markers. Pre-clinical phantom testing was performed to determine the optimum imaging FA-pSAT combination. RESULTS: The iCMR procedure was successfully performed to completion in 31/34 (91%) subjects between August 1st, 2017 to December 13th, 2018. Median age and weight were 7.7 years and 25.2 kg (range: 3 months - 33 years and 8 - 80 kg). Twenty-one subjects had single ventricle (SV) anatomy: one subject was referred for pre-Glenn evaluation, 11 were pre-Fontan evaluations and 9 post-Fontan evaluations for protein losing enteropathy (PLE) and/or cyanosis. Thirteen subjects had bi-ventricular (BiV) anatomy, 4 were referred for coarctation of the aorta (CoA) evaluations, 3 underwent vaso-reactivity testing with inhaled nitric oxide, 3 investigated RV volume dimensions, two underwent branch PA stenosis evaluation, and the remaining subject was status post heart transplant. No catheter related complications were encountered. Average time taken for first pass RHC, LHC/aortic pull back, and to cross the Fontan fenestration was 5.2, 3.0, and 6.5 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 331/337 (98%). Subjects were transferred to the x-ray fluoroscopy lab if further intervention was required including Fontan fenestration device closure, balloon angioplasty of pulmonary arteries/conduits, CoA stenting, and/or coiling of aortopulmonary (AP) collaterals. Starting with subject #10, an MR-conditional guidewire was used in all subsequent subjects (15 SV and 10 BiV) with a success rate of 96% (24/25). Real-time CMR-guided RHC (25/25 subjects, 100%), retrograde and prograde LHC/aortic pull back (24/25 subjects, 96%), CoA crossing (3/4 subjects, 75%) and Fontan fenestration test occlusion (2/3 subjects, 67%) were successfully performed in the majority of subjects when an MR-conditional guidewire was utilized. CONCLUSION: Feasibility for detailed diagnostic RHC, LHC, and Fontan fenestration test occlusion iCMR procedures in SV and BiV pediatric subjects with complex CHD is demonstrated with the aid of an MR-conditional guidewire. A novel real-time pSAT GRE sequence with optimized FA-pSAT angle has facilitated simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures.

Feasibility of real-time cine cardiac magnetic resonance imaging to predict the presence of significant retrosternal adhesions prior to redo-sternotomy.

BACKGROUND: Injury to vital structures posterior to the sternum is a complication associated with redo sternotomy in congenital cardiac surgery. The goal of our study was a novel evaluation of real-time cine cardiovascular magnetic resonance (CMR) to predict the presence of significant retrosternal adhesions of cardiac and vascular structures prior to redo sternotomy in patients with congenital heart disease. METHODS: Twenty-three patients who had prior congenital heart surgery via median sternotomy had comprehensive CMR studies prior to redo sternotomy. The real time cine (RTC) sequence that was used is an ungated balanced steady-state free precession (bSSFP) sequence using SENSitivity Encoding for acceleration with real-time reconstruction. Spontaneously breathing patients were instructed to take deep breaths during the acquisition whilst increased tidal volumes were delivered to mechanically ventilated patients. All patients underwent redo cardiac surgery subsequently and the presence and severity of retrosternal adhesions were noted at the time of the redo sternotomies. RESULTS: Median age at the time of CMR and operation were 5.5 years (range, 0.2-18.4y) and 6.1 years (range, 0.3-18.8y) respectively. There were 15 males and 8 females in the study group. Preoperative retrosternal adhesions were identified on RTC in 13 patients and confirmed in 11 (85%) at the time of surgery. In only 2 patients, no adhesions were identified on CMR but were found to have significant retrosternal adhesions at surgery; false positive rate 15% (CI 0.4-29.6%), false negative rate 20% (CI 3.7-36.4%). The total classification error of the real time cine sequence was 17% (CI 1.7-32.4%) with an overall accuracy of 83% (CI 67.7-98.4%). Standard breath-hold cine images correlated poorly with surgical findings and did not increase the diagnostic yield. CONCLUSIONS: RTC imaging can predict the presence of significant retrosternal adhesions and thus help in risk assessment prior to redo sternotomy. These findings complement the surgical planning and potentially reduce surgical complications .

Validity of Pulmonary Valve Z-Scores in Predicting Valve-Sparing Tetralogy Repairs-Systematic Review †.

There is a lack of consensus regarding the preoperative pulmonary valve (PV) Z-score "cut-off" in tetralogy of Fallot (ToF) patients to attempt a successful valve sparing surgery (VSS). Therefore, the aim of this study was to review the available evidence regarding the association between preoperative PV Z-score and rate of re-intervention for residual right ventricular outflow tract (RVOT) obstruction, i.e. successful valve sparing surgery. A systematic search of studies reporting outcomes of VSS for ToF was performed utilizing PubMed, EMBASE, and Scopus databases. Patients with ToF variants such as pulmonary atresia, major aortopulmonary collaterals, absent pulmonary valve, associated atrioventricular septal defect, and discontinuous pulmonary arteries were excluded. Out of 712 screened publications, 15 studies met inclusion criteria. A total of 1091 patients had surgery at a median age and weight of 6.9 months and 7.2 kg, respectively. VSS was performed on the basis of intraoperative PV assessment in 14 out of 15 studies. The median preoperative PV Z-score was -1.7 (0 to -4.9) with a median re-intervention rate of 4.7% (0-36.8%) during a median follow-up of 2.83 years (1.4-15.8 years). Quantitatively, there was no correlation between decreasing preoperative PV Z-scores and increasing RVOT re-intervention rates with a correlation coefficient of -0.03 and an associated p-value of 0.91. In observational studies, VSS for ToF repair was based on intraoperative evaluation and sizing of the PV following complete relief of all levels of obstruction of the RVOT, rather than pre-operative echocardiography derived PV Z-scores.

Association Between Carotid Intima Media Thickness, Age, and Cardiovascular Risk Factors in Children and Adolescents.

BACKGROUND: Measures of carotid intima media thickness (cIMT) in adults are correlated with adiposity and the metabolic syndrome (MetS) and predict cardiovascular (CV) events. Relations in children are not as well studied. Our objective was to determine the relations of cIMT with body mass index (BMI) and CV risk score in children. METHODS: The study included 291 children (158 M/133 F) 6-18 years of age (140 aged 6-11/151 aged 12-18) with measurements of height, weight, waist circumference; fasting lipids, glucose, insulin, and cIMT. A CV risk cluster score was developed from sum of the z-scores of the five MetS components (waist circumference, blood pressure, serum triglycerides, high-density lipoprotein cholesterol, and insulin). Partial Pearson correlation coefficients were adjusted for age, sex, and race. RESULTS: There was no significant age difference in cIMT from 6 to 18 years of age. BMI and CV risk score were significantly correlated (P < 0.0001), and both were correlated with cIMT (r = 0.14, P = 0.02 and r = 0.16, P = 0.006, respectively). Slight age-related differences in associations of cIMT with CV risk score and BMI were explained by unusual values in a few children. CONCLUSIONS: These cross-sectional data in normal children show that cIMT was stable from childhood into adolescence. However, both BMI and CV risk score had small, but significant positive correlations with cIMT. Therefore, maintaining normal levels of adiposity and other risk variables may be useful in preventing early changes associated with preclinical atherosclerosis.

Heritability of Vascular Structure and Function: A Parent-Child Study.

BACKGROUND: Understanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring. METHODS AND RESULTS: High-resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow-mediated dilation were measured in the brachial artery. Intima-media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross-sectional distensibility were measured, and carotid cross-sectional compliance was measured in the carotid artery. Carotid-radial pulse wave velocity was obtained using SphygmoCor®. Heritability analysis (h2, expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body-mass index, smoking, and mean arterial pressure. Data are presented as mean±SE. Measures of brachial artery diameter (h2=25±9%, P=0.001), lumen diameter (h2=55±9%, P<0.001), intima-media thickness (h2=29±13%, P=0.014), diameter distensibility (h2=28±7%, P<0.001), cross-sectional distensibility (h2=27±7%, P<0.001), and pulse wave velocity (h2=26±9%, P<0.001) were significantly heritable. Flow-mediated dilation and incremental elastic modulus were not significantly heritable. Similar associations were observed in analysis restricted to siblings and complete Trios (mother, father, and child). CONCLUSIONS: These data show that the majority of noninvasive measures of vascular structure and function are heritable, suggesting that measurement of these subclinical risk factors in parents may be helpful in assessing childhood risk for future cardiovascular disease.

Patient-Specific MRI-Based Right Ventricle Models Using Different Zero-Load Diastole and Systole Geometries for Better Cardiac Stress and Strain Calculations and Pulmonary Valve Replacement Surgical Outcome Predictions.

BACKGROUND: Accurate calculation of ventricular stress and strain is critical for cardiovascular investigations. Sarcomere shortening in active contraction leads to change of ventricular zero-stress configurations during the cardiac cycle. A new model using different zero-load diastole and systole geometries was introduced to provide more accurate cardiac stress/strain calculations with potential to predict post pulmonary valve replacement (PVR) surgical outcome. METHODS: Cardiac magnetic resonance (CMR) data were obtained from 16 patients with repaired tetralogy of Fallot prior to and 6 months after pulmonary valve replacement (8 male, 8 female, mean age 34.5 years). Patients were divided into Group 1 (n = 8) with better post PVR outcome and Group 2 (n = 8) with worse post PVR outcome based on their change in RV ejection fraction (EF). CMR-based patient-specific computational RV/LV models using one zero-load geometry (1G model) and two zero-load geometries (diastole and systole, 2G model) were constructed and RV wall thickness, volume, circumferential and longitudinal curvatures, mechanical stress and strain were obtained for analysis. Pairwise T-test and Linear Mixed Effect (LME) model were used to determine if the differences from the 1G and 2G models were statistically significant, with the dependence of the pair-wise observations and the patient-slice clustering effects being taken into consideration. For group comparisons, continuous variables (RV volumes, WT, C- and L- curvatures, and stress and strain values) were summarized as mean ± SD and compared between the outcome groups by using an unpaired Student t-test. Logistic regression analysis was used to identify potential morphological and mechanical predictors for post PVR surgical outcome. RESULTS: Based on results from the 16 patients, mean begin-ejection stress and strain from the 2G model were 28% and 40% higher than that from the 1G model, respectively. Using the 2G model results, RV EF changes correlated negatively with stress (r = -0.609, P = 0.012) and with pre-PVR RV end-diastole volume (r = -0.60, P = 0.015), but did not correlate with WT, C-curvature, L-curvature, or strain. At begin-ejection, mean RV stress of Group 2 was 57.4% higher than that of Group 1 (130.1±60.7 vs. 82.7±38.8 kPa, P = 0.0042). Stress was the only parameter that showed significant differences between the two groups. The combination of circumferential curvature, RV volume and the difference between begin-ejection stress and end-ejection stress was the best predictor for post PVR outcome with an area under the ROC curve of 0.855. The begin-ejection stress was the best single predictor among the 8 individual parameters with an area under the ROC curve of 0.782. CONCLUSION: The new 2G model may be able to provide more accurate ventricular stress and strain calculations for potential clinical applications. Combining morphological and mechanical parameters may provide better predictions for post PVR outcome.

Mechanical stress is associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot.

OBJECTIVE: Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement. METHODS: Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis. RESULTS: Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1. CONCLUSIONS: Computational modeling and right ventricular stress may be used as tools to identify right ventricular function response to pulmonary valve replacement. Large-scale clinical studies are needed to validate these preliminary findings.

Comparison of pediatric patients with status epilepticus lasting 5-29 min versus ≥30 min.

The most common thresholds for considering prolonged seizures as status epilepticus (SE) are 5 and 30 min. It is unknown whether these different thresholds (5 or 30 min) identify patient populations with different electroclinical characteristics. We compared the characteristics of patients with SE lasting 5-29 min (SE5-29) with those with SE lasting ≥30 min (SE≥30). Inclusion criteria were the following: 1) 1 month to 21 years of age at the time of SE, 2) convulsive seizures, and 3) seizure duration ≥5 min. Exclusion criteria were the following: 1) exclusively neonatal seizures, 2) psychogenic nonepileptic seizures, or 3) incomplete information about seizure duration. Four hundred forty-five patients (50.1% male) with a median (p25-p75) age at SE of 5.5 (2.8-10.5) years were enrolled. Status epilepticus lasted for 5-29 min in 296 (66.5%) of subjects and for ≥30 min in 149 (33.5%). Patients with SE≥30 were younger than the patients with SE5-29 at the time of seizure onset (median: 1 versus 2.1 years, p=0.0007). Status epilepticus as the first seizure presentation was more frequent in patients with SE≥30 (24.2% versus 12.2%, p=0.002). There was a tendency towards a higher rate of abnormalities in the magnetic resonance imaging at baseline in patients with SE≥30 (70.5% versus 57.1%, p=0.061). Differences were not detected in seizure frequency, seizure types, presence of developmental delay, and electroencephalogram abnormalities at baseline. In the pediatric population, SE thresholds of either 5 or 30 min identify groups of patients with very similar electroclinical characteristics, which may influence future definitions of pediatric SE.

Clinical application and evaluation of the Bien diagnostic criteria for Rasmussen encephalitis.

PURPOSE: The 2005 diagnostic criteria for Rasmussen encephalitis (RE) are based on seizures, clinical deficits, electroencephalography (EEG), neuroimaging, and pathology (Brain, 128, 2005, 451). We applied these criteria to patients evaluated for RE and epilepsy surgery controls to determine the sensitivity, specificity, and positive and negative predictive values (PPVs, NPVs) using pathology as the gold standard. METHODS: We identified patients evaluated for RE based on medical records from 1993 to 2011. Fifty-two control patients with refractory epilepsy, unilateral magnetic resonance imaging (MRI) changes, and biopsies were selected from an epilepsy surgery database from matching years. Patients meeting all three of group A and/or two of three group B criteria were classified as meeting full criteria (positive). Patients not meeting full criteria were classified as negative. When available, pathology findings were re-reviewed with neuropathologists, and MRI imaging was re-reviewed with a neuroradiologist. KEY FINDINGS: RE was considered in the differential diagnosis for 82 patients, of whom 35 had biopsies. Twenty patients met full criteria (positive) without another explanation, including seven for whom biopsy was required to meet criteria and one in whom another etiology was identified. Two patients met full criteria but had another explanation. Thirty-five met partial criteria (negative), of whom 14 had another etiology identified. Twenty-five met no criteria (negative). The diagnostic criteria had a sensitivity of 81% with four false negatives (criteria-negative, biopsy-positive) when compared to pathology as a gold standard. Five false positives (criteria positive, biopsy negative) had identifiable alternate diagnoses. SIGNIFICANCE: The 2005 Bien clinical diagnostic criteria for RE have reasonably high sensitivity and specificity and good clinical-pathologic correlation in most cases. We suggest modification of the criteria to allow inclusion of cases with well-described but less common features. Specifically we suggest making the diagnosis in the absence of epilepsia partialis continua (EPC) or clear progression of focal cortical deficits or MRI findings if biopsy is positive and two of the A criteria are met (B3 plus two of three A criteria). This would improve the sensitivity of the criteria.

A Multiphysics Modeling Approach to Develop Right Ventricle Pulmonary Valve Replacement Surgical Procedures with a Contracting Band to Improve Ventricle Ejection Fraction.

Patients with repaired tetralogy of Fallot account for the majority of cases with late onset right ventricle (RV) failure. A new surgical procedure placing an elastic band in the right ventricle is proposed to improve RV function measured by ejection fraction. A multiphysics modeling approach is developed to combine cardiac magnetic resonance imaging, modeling, tissue engineering and mechanical testing to demonstrate feasibility of the new surgical procedure. Our modeling results indicated that the new surgical procedure has the potential to improve right ventricle ejection fraction by 2-7% which compared favorably with recently published drug trials to treat LV heart failure.

Using contracting band to improve right ventricle ejection fraction for patients with repaired tetralogy of Fallot: a modeling study using patient-specific CMR-based 2-layer anisotropic models of human right and left ventricles.

OBJECTIVE: Patients with repaired tetralogy of Fallot account for most cases of late-onset right ventricle failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. A new surgical option of placing an elastic band in the right ventricle is proposed to improve right ventricular cardiac function as measured by the ejection fraction. METHODS: A total of 20 computational right ventricular/left ventricular/patch/band combination models using cardiac magnetic resonance imaging from a patient with tetralogy of Fallot were constructed to investigate the effect of band material stiffness variations, band length, and active contraction. These models included 4 different band material properties, 3 band length, 3 active contracting band materials, and models with patch and scar replaced by contracting tissue. RESULTS: Our results indicated that the band insertion, combined with active band contraction and tissue regeneration techniques that restore right ventricular myocardium, has the potential to improve right ventricular ejection fraction by 7.5% (41.63% ejection fraction from the best active band model to more than 34.10% ejection fraction from baseline passive band model) and 4.2% (41.63% from the best active band model compared with cardiac magnetic resonance imaging-measured ejection fraction of 37.45%). CONCLUSIONS: The cardiac magnetic resonance imaging-based right ventricular/left ventricular/patch/band model provides a proof of concept for using elastic bands to improve right ventricular cardiac function. Band insertion, combined with myocardium regeneration techniques and right ventricular remodeling surgical procedures, has the potential to improve ventricular function in patients with repaired tetralogy of Fallot and other similar forms of right ventricular dysfunction after surgery. Additional investigations using in vitro experiments, animal models, and, finally, patient studies are warranted.

Experience with lacosamide in a series of children with drug-resistant focal epilepsy.

We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n=3), vagus nerve stimulation (n=9), and ketogenic diet (n=3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n=10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P<0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (≥50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with ≥50% seizure reduction) without severe adverse events.

Experience with rufinamide in a pediatric population: a single center's experience.

Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes.