Faculty Bibliography

BACKGROUND:Stroke is the most feared complication associated with the Berlin Heart EXCOR pediatric ventricular assist device (VAD), the most commonly used VAD in children, and affects 1 in 3 children. We sought to determine whether a modified anti-thrombotic guideline, involving more intense platelet inhibition and less reliance on platelet function testing, is associated with a lower incidence of stroke. METHODS:All children supported with the EXCOR at Stanford from 2009 to 2014 were divided into 2 cohorts based on the primary anti-thrombotic guideline used to prevent pump thrombosis: (1) the Edmonton Anti-thrombotic Guideline (EG) cohort, which included children implanted before September 2012 when dual anti-platelet therapy was used with doses titrated to Thromboelastrography/PlateletMapping (TEG/PM); and (2) the Stanford Modified Anti-thrombotic Guideline (SG) cohort, which included children implanted on or after September 2012 when triple anti-platelet therapy was used routinely and where doses were uptitrated to high, weight-based dosing targets, with low-dose steroids administered as needed for inflammation. RESULTS:At baseline, the EG (N = 16) and SG (N = 11) cohorts were similar. The incidence rate of stroke in the SG cohort was 84% lower than in the EG cohort (0.8 vs 4.9 events per 1,000 days of support, p = 0.031), and 86% lower than in the previous Investigational Device Exemption trial (p = 0.006). The bleeding rate was also lower in the SG cohort (p = 0.015). Target doses of aspirin, clopidogrel and dipyridamole were higher (all p < 0.003), with less dosing variability in the SG cohort than in the EG cohort. There was no difference in adenosine diphosphate inhibition by TEG/PM, but arachidonic acid inhibition was higher in the SG cohort (median 75% vs 39%, p = 0.008). CONCLUSIONS:Stroke was significantly less common in pediatric patients supported with the Berlin Heart EXCOR VAD using a triple anti-platelet regimen uptitrated to high, weight-based dosing targets as compared with the dual anti-platelet regimen titrated to PM, and without a higher risk of bleeding. Larger studies are needed to confirm these findings.

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern in the United States with high prevalence, growing incidence, and serious adverse outcomes. OBJECTIVE: We aimed to develop and validate a model to identify patients at risk of receiving a new diagnosis of CKD (incident CKD) during the next 1 year in a general population. METHODS: The study population consisted of patients who had visited any care facility in the Maine Health Information Exchange network any time between January 1, 2013, and December 31, 2015, and had no history of CKD diagnosis. Two retrospective cohorts of electronic medical records (EMRs) were constructed for model derivation (N=1,310,363) and validation (N=1,430,772). The model was derived using a gradient tree-based boost algorithm to assign a score to each individual that measured the probability of receiving a new diagnosis of CKD from January 1, 2014, to December 31, 2014, based on the preceding 1-year clinical profile. A feature selection process was conducted to reduce the dimension of the data from 14,680 EMR features to 146 as predictors in the final model. Relative risk was calculated by the model to gauge the risk ratio of the individual to population mean of receiving a CKD diagnosis in next 1 year. The model was tested on the validation cohort to predict risk of CKD diagnosis in the period from January 1, 2015, to December 31, 2015, using the preceding 1-year clinical profile. RESULTS: The final model had a c-statistic of 0.871 in the validation cohort. It stratified patients into low-risk (score 0-0.005), intermediate-risk (score 0.005-0.05), and high-risk (score >/= 0.05) levels. The incidence of CKD in the high-risk patient group was 7.94%, 13.7 times higher than the incidence in the overall cohort (0.58%). Survival analysis showed that patients in the 3 risk categories had significantly different CKD outcomes as a function of time (P<.001), indicating an effective classification of patients by the model. CONCLUSIONS: We developed and validated a model that is able to identify patients at high risk of having CKD in the next 1 year by statistically learning from the EMR-based clinical history in the preceding 1 year. Identification of these patients indicates care opportunities such as monitoring and adopting intervention plans that may benefit the quality of care and outcomes in the long term.

BACKGROUND:Follow-up of transcatheter pulmonary valve replacement (TPVR) with the Melody valve has demonstrated good short-term and long-term outcomes, but there are no published studies focused on valve performance in the Contegra bovine jugular vein conduit. METHODS AND RESULTS/RESULTS:<0.001). The incidence of Melody transcatheter pulmonary valve stent fracture (3.4%) and infectious endocarditis (4.3%) were both low. Serious adverse events occurred in 3 patients. CONCLUSIONS:Melody TPVR in Contegra conduits is safe and effective and can be performed in a wide range of conduit sizes with preserved valve function and low incidence of stent fracture and endocarditis.

Rapid prototyping facilitates comprehension of complex cardiac anatomy. However, determining when this additional information proves instrumental in patient management remains a challenge. We describe our experience with patient-specific anatomic models created using rapid prototyping from various imaging modalities, suggesting their utility in surgical and interventional planning in congenital heart disease (CHD). Virtual and physical 3-dimensional (3D) models were generated from CT or MRI data, using commercially available software for patients with complex muscular ventricular septal defects (CMVSD) and double-outlet right ventricle (DORV). Six patients with complex anatomy and uncertainty of the optimal management strategy were included in this study. The models were subsequently used to guide management decisions, and the outcomes reviewed. 3D models clearly demonstrated the complex intra-cardiac anatomy in all six patients and were utilized to guide management decisions. In the three patients with CMVSD, one underwent successful endovascular device closure following a prior failed attempt at transcatheter closure, and the other two underwent successful primary surgical closure with the aid of 3D models. In all three cases of DORV, the models provided better anatomic delineation and additional information that altered or confirmed the surgical plan. Patient-specific 3D heart models show promise in accurately defining intra-cardiac anatomy in CHD, specifically CMVSD and DORV. We believe these models improve understanding of the complex anatomical spatial relationships in these defects and provide additional insight for pre/intra-interventional management and surgical planning.

INTRODUCTION Melody transcatheter pulmonary valve (TPV) implantation is frequently considered in patients with Right Ventricle Outflow Tract (RVOT) conduit obstruction, as a minimally invasive alternative to open-heart surgery.1 However, TPV implantation is associated to a risk of coronary artery (CA) compression.2 In this work, an innovative Finite Element (FE) balloon dilatation model has been built to predict CA compression in order to avoid patient exposure to unnecessary risks. In this study four patients, who underwent MRI or CT in anticipation to receive TPV, were considered. Images were segmented to generate 3D models. A balloon dilatation FE simulation was implemented for each of the models. The balloon was represented as a deformable 3D cylinder positioned at the center of mass at the narrowest point of the conduit lumen. Then, radial displacement was applied uniformly until the balloon reached the dimension of a fully inflated balloon. A linear elastic constitutive model was chosen to describe all the vasculature, and parameters for it were retrieved from literature. A frictionless contact algorithm was implemented between the balloon and the conduit and between the conduit and the surrounding structures. The results of the simulations allowed analysis of important parameters that could play an active role in the determination of the angioplasty procedure outcome in terms of CA compression. MATERIALS AND METHODS Patient-Specific Models Patients who were candidates for Transcatheter Pulmonary Valve Replacement (TPVR) were included (n = 4). The investigators from Tandon School of Engineering were blinded to the results of the procedure. Each patient underwent pre-catheterization Magnetic Resonance Imaging (MRI) or Computerized Tomography scan (CT scan) and patient-specific models were created from these images using Mimics (Materialize, Belgium), Meshmixer (Autodesk, California) and Cubit (C Sim Software, Utah) software. Each model was constituted by the components of the cardiovascular system affected by the angioplasty procedure, the pulmonary artery (PA), the aorta and the coronary arteries (CA). A 60 mm long segment of PA was selected from the right ventricle outflow tract (RVOT) to the PA bifurcation so that the conduit was included. Similarly, a 60 mm long segment of aorta was selected from the aortic root to the aortic arch. Finally, left and right CAs were selected where visible. Our protocol required the CA branches to be at least 20 mm in length to be included in the study. The model thus obtained, was manipulated using 3D CAD tools available in Meshmixer to smooth the model and to generate a 3D hollow geometry from a model representing only the blood pool. The hollowing procedure required the definition of the thickness of the arterial wall, which was chosen to be 2 mm for the aorta and the RVOT conduit, and 1 mm for the CA branches,3 see Fig. 1A-D. Finally, the model was meshed using Cubit. The PA model was divided in three parts: a 30 mm long central section that defined the contact surfaces, internally with the balloon and externally with the aorta and CAs; and the two remaining parts, each 15 mm long, extending before and after the contact area. Tetrahedral elements where used for meshing the models, and in average, the number of elements used was 14,406 +/- 5875. The model thus obtained was then exported in ABAQUS (Dassault Systemes, RI) for the finite element simulations. Balloon Models In this study, two separate approaches were used to model the angioplasty balloon. In one case an analytical rigid surface is used to simulate the balloon, and the results of this approach are compared with a deformable balloon model. * Rigid Balloon In order to replicate folding of the angioplasty balloon into a catheter, the rigid balloon model was composed by 5 analytical rigid surfaces made in such a way that, after the applied radial displacement, the shells were forming a cylinder with a diameter matching that of an inflated angioplasty balloon, see Fig. 1E. * Deformable Balloon The deformable balloon model was created in ABAQUS. In this case, the balloon was modeled as a deformable 3D cylinder of 20 mm length, 1 mm of external diameter and 0.2 mm thickness.1 A mesh of 63 quadrilateral elements was generated and solved by employing reduced integration algorithms and large-strain formulation, see Fig. 1F. Material Models Human arterial tissue was modeled as a linear-elastic isotropic material with Young's modulus of 2.7 MPa and Poisson ratio of 0.49.4Duetothe lack of data on thematerialproperties of the conduit after implantation, the material properties of the conduit were assumed to be similar to those of the arterial tissue. Based on literature, the balloon was modeled as an isotropic, linear-elastic material, with a Young's modulus of 900 MPa and Poisson's ratio of 0.3.5-6 Contact Definition Each model surface was defined and surface-to-surface frictionless hard contact was imposed between the external surface of the balloon model and the internal surface of the conduit. Surface to surface frictionless hard contact was also imposed between the external pulmonary artery surface external surface of the aorta and the CA. The contact model used assumed that: (1) the surfaces transmit no contact pressure unless the nodes of the slave-surface contact the master-surface; (2) no penetration is allowed at each surface; (3) there is no limit to the magnitude of contact pressure that can be transmitted when the surfaces are in contact. The direct method was chosen as contact constraint enforcement method. Surface to surface contact was used such that the master role was given to the surface with the coarser mesh and/or larger area. For the analyses with analytical rigid surfaces, the master role was always given to the rigid shell. Boundary Conditions All the extremities of the conduit and of the aorta are constrained through an encastre. The extremity at the end of the CA is constrained as well through an encastre. Displacement Protocol The angioplasty intervention was simulated by displacing the balloon to the diameter used during the intervention. Although the TPVR standard protocol, states that the angioplasty balloon can be inflated to 110% of the original conduit diameter or 24 mm,1,2 whichever is greater, this protocol could be applied only to patient 2, see Fig. 1G. RESULTS For all the simulations, the balloon expanded under the imposed displacement conditions causing the conduit to deform. As the balloon displacement was increased, the central part of the conduit also expanded. It was also noticeable that once the balloon had reached its nominal diameter, the maximum stress value was localized in the portion of the conduit with the highest curvature for all four models. Rigid Balloon vs Deformable Balloon By comparing the two different approaches to model angioplasty, it was found that more stable results were obtained using the meshed cylinder balloon model rather than the one made of analytically rigid surfaces. However, it was possible to compare the results of the two models for deformations up to the 80% of the complete final angioplasty balloon diameter. Results on the conduit in terms of stress and deformation were strongly comparable. In fact, the average Von Mises stress varied by 0.76%, while the average displacement varied by 0.3%. In both cases the values obtained in the deformable model were smaller than the ones obtained in the rigid one. Angioplasty Outcomes For all the patient-specific models we evaluated whether CA compression could be modeled with this approach. The results show that in two cases the CA deforms, but there is no contact with the conduit. In these cases, we defined the CA to be distorted and not compressed as it deforms as a consequence of compression at the level of the aortic root, see Fig. 2A-D. DISCUSSION Segmentation of the patient geometries generated regular models, which made possible to complete the computational analysis. Overall, 50% of the sample population analyzed showed the risk of coronary deformation as a result of the angioplasty balloon expansion. Computational methods, such as the finite element method, represent an interesting alternative to the state-of-art catheterization lab evaluation, which have been found to have a low prediction value. The results of the four expansion simulations presented similar values of the maximum Von Mises stresses on the pulmonary arteries, while they present different results in terms of displacement and stresses in the coronary arteries, showing that coronary compression is strictly dependent on the specific geometry on the specific patient. CONCLUSIONS In this study, the effect of the balloon expansion during pre- TPV Angioplasty procedure was investigated by means of the FE method. Data of four patients who underwent attempted MelodyTM valve implantation were used. A deformable cylindrical balloon model was developed and compared with a balloon model constituted by analytical rigid shells to evaluate whether the choice of a different balloon model can be significant in terms of displacement results in the artery. The developed models allowed analysis of important parameters that could play a role in the determination on the angioplasty procedure outcome in terms of coronary compression. Finally, this work successfully identified a method to simulate a pre-TPVR procedure. Future work includes the analysis of a pressure based balloon expansion. This approach would be closer to the actual procedure and make possible the realization of a folded balloon model obtained by applying a negative pressure from a cylindrical configuration.(Table Presented)

BACKGROUND: Diabetes case finding based on structured medical records does not fully identify diabetic patients whose medical histories related to diabetes are available in the form of free text. Manual chart reviews have been used but involve high labor costs and long latency. OBJECTIVE: This study developed and tested a Web-based diabetes case finding algorithm using both structured and unstructured electronic medical records (EMRs). METHODS: This study was based on the health information exchange (HIE) EMR database that covers almost all health facilities in the state of Maine, United States. Using narrative clinical notes, a Web-based natural language processing (NLP) case finding algorithm was retrospectively (July 1, 2012, to June 30, 2013) developed with a random subset of HIE-associated facilities, which was then blind tested with the remaining facilities. The NLP-based algorithm was subsequently integrated into the HIE database and validated prospectively (July 1, 2013, to June 30, 2014). RESULTS: Of the 935,891 patients in the prospective cohort, 64,168 diabetes cases were identified using diagnosis codes alone. Our NLP-based case finding algorithm prospectively found an additional 5756 uncodified cases (5756/64,168, 8.97% increase) with a positive predictive value of .90. Of the 21,720 diabetic patients identified by both methods, 6616 patients (6616/21,720, 30.46%) were identified by the NLP-based algorithm before a diabetes diagnosis was noted in the structured EMR (mean time difference = 48 days). CONCLUSIONS: The online NLP algorithm was effective in identifying uncodified diabetes cases in real time, leading to a significant improvement in diabetes case finding. The successful integration of the NLP-based case finding algorithm into the Maine HIE database indicates a strong potential for application of this novel method to achieve a more complete ascertainment of diagnoses of diabetes mellitus.

We report a rare case of progressive left ventricular outflow tract (LVOT) obstruction after percutaneous device closure of a mechanical prosthetic mitral valve (MV) paravalvular leak (PVL) in the region of aortomitral curtain in a patient who also had small mechanical aortic valve prosthesis with patient-prosthesis mismatch.

Transcatheter pulmonary valve replacement (TPVR) is an important treatment option in repaired tetralogy of Fallot (TOF) and right ventricular outflow tract (RVOT) dysfunction. Indications for timing of TPVR are extrapolated from surgical pulmonary valve replacement guidelines, which are themselves controversial as published evidence is scarce and expert opinion therefore prevails. We review current indications for PVR following TOF repair, focusing on those for TPVR specifically, and discuss anatomical and functional considerations as these pertain to determination of candidacy for TPVR. Hemodynamic assessment surrounding PVR has focused on assessment of the right ventricle (RV) size and systolic function, with the goal of intervening in the asymptomatic patient prior to the development of irreversible RV deterioration and right heart failure. The impact of abnormal RV mechanics on the LV has been appreciated, with the assessment of LV function assuming higher priority in decision-making regarding possible PVR. In addition to the standard volumetric assessment, evaluation with indices of myocardial wall strain, tissue velocities, diastology, and ventricular response to exercise is emerging as tools with potential to further refine timing of PVR. We conclude that, at present, current evidence, although limited, supports a more aggressive approach in those who meet inclusion for TPVR in patients with repaired TOF and RVOT dysfunction guided by the discussed hemodynamic assessment, however, more importantly this review should lay the framework for future investigations regarding hemodynamic assessment of this population.

Ascending aortic and subvalvar left ventricular outflow tract (LVOT) pseudoaneurysms are rare complications following aortic valve or root replacement surgery. Clinically important paravalvular leaks are rare complications following any valve replacement surgery. We report an unusual case of sequential percutaneous closure of mitral prosthetic paravalvular leak and complex communicating ascending aortic and subvalvar LVOT pseudoaneurysms, which demonstrates the importance of multimodal imaging assessment surrounding percutaneous closure. (c) 2015 Wiley Periodicals, Inc.

We report a case of retrograde transcatheter device closure of a complex paravalvular leak (PVL) after bioprosthetic pulmonary valve replacement (PVR) in a 13-year-old patient with congenital pulmonary valve stenosis. There are prior reports of pulmonary PVL closure after PVR in adults (Seery and Slack, Congenit Heart Dis 2014;9:E19-F22), but indications for and technical considerations in PVL closure after bioprosthetic PVR, particularly in children, are not well defined. (c) 2015 Wiley Periodicals, Inc.