Gorman Cardiovascular Research Group

Philadelphia, PA, United States

Gorman Cardiovascular Research Group

Philadelphia, PA, United States
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Bouma W.,University of Pennsylvania | Bouma W.,University of Groningen | Aoki C.,University of Pennsylvania | Vergnat M.,University of Pennsylvania | And 8 more authors.
Annals of Thoracic Surgery | Year: 2015

Background Current repair results for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings are characterized by high IMR recurrence rates. Current annuloplasty rings treat annular dilatation, but they do little to improve (and may actually exacerbate) leaflet tethering. New saddle-shaped annuloplasty rings have been shown to maintain or restore a more physiologic annular and leaflet geometry and function. Using a porcine IMR model, we sought to demonstrate the influence of annuloplasty ring shape on leaflet coaptation. Methods Eight weeks after posterolateral infarct, eight pigs with grade 2+ or higher IMR were randomized to undergo either a 28-mm flat ring annuloplasty (n = 4) or a 28-mm saddle-shaped ring annuloplasty (n = 4). Real-time three-dimensional echocardiography and a customized image analysis protocol allowed three-dimensional assessment of leaflet coaptation before and after annuloplasty. Results Total leaflet coaptation area was significantly higher after saddle-shaped ring annuloplasty (109.6 ± 26.9 mm2) compared with flat ring annuloplasty (46.2 ± 7.7 mm2, p <0.01). After annuloplasty, total coaptation area decreased by 87.5 mm2 (or 65%) in the flat annuloplasty group (p = 0.01), whereas total coaptation area increased by 22.2 mm2 (or 25%) in the saddle-shaped annuloplasty group (p = 0.28). Conclusions This study shows that the use of undersized saddle-shaped annuloplasty rings in mitral valve repair for IMR improves leaflet coaptation, whereas the use of undersized flat annuloplasty rings worsens leaflet coaptation. Because one of Carpentier's fundamental principles of mitral valve repair (durability) is to create a large surface of coaptation, saddle-shaped annuloplasty may increase repair durability. © 2015 The Society of Thoracic Surgeons.


Robb J.D.,Gorman Cardiovascular Research Group | Minakawa M.,Gorman Cardiovascular Research Group | Rodriguez E.,Children's Hospital of Philadelphia | Rodriguez E.,East Carolina University | And 5 more authors.
Circulation: Cardiovascular Interventions | Year: 2011

Background-Transannular patch (TAP) repair of tetralogy of Fallot often results in significant right ventricular outflow tract (RVOT) dilation and distortion. We hypothesized that insertion of Melody valves into the proximal right and left branch pulmonary arteries (PAs) would reduce pulmonary regurgitation fraction (PRF) in an ovine model of pulmonary insufficiency and dilated RVOT. Methods and Results-Ten sheep underwent baseline cardiac catheterization, surgical pulmonary valvectomy, and TAP placement. A subset (n=5) had Melody valves (2 devices per animal) inserted into the proximal right and left PAs during the surgical procedure. Melody valves were placed distal to the right-upper-lobe (RUL) artery branch, leaving the RUL "unprotected. " Preoperative MRIs (n=5) were used to determine baseline RV ejection fraction (RVEF) and left ventricular (LV) EF. All surviving animals (n=9) underwent MRI and catheterization 6 weeks postsurgery. Mean PRF was lower in the Melody valve group (15±6% versus 37±3%; P=0.014). The unprotected RUL was responsible for 64% of the PRF measured in the Melody valve group. In the non-Melody group, the RVEF was lower than baseline (P=0.003) and than in the Melody group (P=0.05). The LVEF was also lower in the non-Melody group versus baseline (P=0.004) and versus Melody (P=0.01). Conclusions-Bilateral branch PA Melody valve implantation significantly reduced PRF and altered RV and LV function favorably in a model of TAP for tetralogy of Fallot. This novel intervention may offer potential benefit in treating patients with anatomically heterogeneous disease of the RVOT. © 2011 American Heart Association, Inc.


Levack M.M.,Gorman Cardiovascular Research Group | Jassar A.S.,Gorman Cardiovascular Research Group | Jassar A.S.,University of Pennsylvania | Shang E.K.,University of Pennsylvania | And 8 more authors.
Circulation | Year: 2012

Background-Proponents of flexible annuloplasty rings have hypothesized that such devices maintain annular dynamics. This hypothesis is based on the supposition that annular motion is relatively normal in patients undergoing mitral valve repair. We hypothesized that mitral annular dynamics are impaired in ischemic mitral regurgitation and myxomatous mitral regurgitation. Methods and Results-A Philips iE33 echocardiographic module and X7-2t probe were used to acquire full-volume real-time 3-dimensional transesophageal echocardiography loops in 11 normal subjects, 11 patients with ischemic mitral regurgitation and 11 patients with myxomatous mitral regurgitation. Image analysis was performed using Tomtec Image Arena, 4D-MV Assessment, 2.1 (Munich, Germany). A midsystolic frame was selected for the initiation of annular tracking using the semiautomated program. Continuous parameters were normalized in time to provide for uniform systolic and diastolic periods. Both ischemic mitral regurgitation (9.98±155 cm) and myxomatous mitral regurgitation annuli (13.29±3.05 cm) were larger in area than normal annuli (7.95±1.40 cm) at midsystole. In general, ischemic mitral regurgitation annuli were less dynamic than controls. In myxomatous mitral regurgitation, annular dynamics were also markedly abnormal with the mitral annulus dilating rapidly in early systole in response to rising ventricular pressure. Conclusions-In both ischemic mitral regurgitation and myxomatous mitral regurgitation, annular dynamics and anatomy are abnormal. Flexible annuloplasty devices used in mitral valve repair are, therefore, unlikely to result in either normal annular dynamics or normal anatomy. © 2012 American Heart Association, Inc.


Macarthur J.W.,Gorman Cardiovascular Research Group | Macarthur J.W.,Stanford University | Cohen J.E.,Gorman Cardiovascular Research Group | Cohen J.E.,Stanford University | And 18 more authors.
Circulation Research | Year: 2014

RATIONALE:: After myocardial infarction, there is an inadequate blood supply to the myocardium, and the surrounding borderzone becomes hypocontractile. OBJECTIVE:: To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of myocardial infarction, the modified endothelial progenitor stem cell chemokine, engineered stromal cell-derived factor 1α analog (ESA), would induce endothelial progenitor stem cell chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility. METHODS AND RESULTS:: Thirty-six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction, and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac MRI and pressure-volume catheter transduction. Bone marrow was harvested for in vitro analysis, and myocardial biopsies were taken for mRNA, protein, and immunohistochemical analysis. ESA induced greater chemotaxis of endothelial progenitor stem cells compared with saline (P<0.01) and was equivalent to recombinant stromal cell-derived factor 1α (P=0.27). Analysis of mRNA expression and protein levels in ESA-treated animals revealed reduced matrix metalloproteinase 2 in the borderzone (P<0.05), with elevated levels of tissue inhibitor of matrix metalloproteinase 1 and elastin in the infarct (P<0.05), whereas immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (P<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (P<0.01), increased maximal principle strain in the borderzone (P<0.01), and a steeper slope of the end-systolic pressure-volume relationship (P=0.01). CONCLUSIONS:: The novel, biomolecularly designed peptide ESA induces chemotaxis of endothelial progenitor stem cells, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of myocardial infarction. © 2014 American Heart Association, Inc.


Gillespie M.J.,Gorman Cardiovascular Research Group | Gillespie M.J.,Children's Hospital of Philadelphia | Aoki C.,Gorman Cardiovascular Research Group | Aoki C.,University of Pennsylvania | And 10 more authors.
Annals of Thoracic Surgery | Year: 2015

Purpose We describe our initial experience with on-bypass and off-bypass (off-pump) mitral valve replacement with the modified version of our novel catheter-based sutureless mitral valve (SMV) technology, which was developed to atraumatically anchor and seal in the mitral position. Description The SMV is a self-expanding device consisting of a custom designed nitinol framework and a pericardial leaflet valve mechanism. For the current studies, our original device was modified (SMV2) to reduce the delivery profile and to allow for controlled deployment while still maintaining the key principles necessary for atraumatic anchoring and sealing in the mitral valve position. Evaluation Ten Yorkshire pigs underwent successful SMV2 device implantation through a left atriotomy (on-pump, n = 6; off-pump, n = 4). Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Postmortem examination demonstrated that the SMV2 devices were anchored securely. Conclusions This study demonstrates the feasibility and short-term success of off-pump mitral valve replacement using a novel, catheter-based device in a porcine model. © 2015 The Society of Thoracic Surgeons.


Xu C.,Gorman Cardiovascular Research Group | Brinster C.J.,University of Pennsylvania | Jassar A.S.,Gorman Cardiovascular Research Group | Jassar A.S.,University of Pennsylvania | And 7 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2010

Three-dimensional (3-D) echocardiography allows the generation of anatomically correct and time-resolved geometric mitral valve (MV) models. However, as imaged in vivo, the MV assumes its systolic geometric configuration only when loaded. Customarily, finite element analysis (FEA) is used to predict material stress and strain fields rendered by applying a load on an initially unloaded model. Therefore, this study endeavors to provide a framework for the application of in vivo MV geometry and FEA to MV physiology, pathophysiology, and surgical repair. We hypothesize that in vivo MV geometry can be reasonably used as a surrogate for the unloaded valve in computational (FEA) simulations, yielding reasonable and meaningful stress and strain magnitudes and distributions. Three experiments were undertaken to demonstrate that the MV leaflets are relatively nondeformed during systolic loading: 1) leaflet strain in vivo was measured using sonomicrometry in an ovine model, 2) hybrid models of normal human MVs as constructed using transesophageal real-time 3-D echocardiography (rt-3DE) were repeatedly loaded using FEA, and 3) serial rt-3DE images of normal human MVs were used to construct models at end diastole and end isovolumic contraction to detect any deformation during isovolumic contraction. The average linear strain associated with isovolumic contraction was 0.02 ± 0.01, measured in vivo with sonomicrometry. Repeated loading of the hybrid normal human MV demonstrated little change in stress or geometry: peak von Mises stress changed by <4% at all locations on the anterior and posterior leaflets. Finally, the in vivo human MV deformed minimally during isovolumic contraction, as measured by the mean absolute difference calculated over the surfaces of both leaflets between serial MV models: 0.53 ± 0.19 mm. FEA modeling of MV models derived from in vivo high-resolution truly 3-D imaging is reasonable and useful for stress prediction in MV pathologies and repairs. Copyright © 2010 the American Physiological Society.


Gillespie M.J.,Children's Hospital of Philadelphia | Gillespie M.J.,Gorman Cardiovascular Research Group | Minakawa M.,Gorman Cardiovascular Research Group | Minakawa M.,University of Pennsylvania | And 22 more authors.
Annals of Thoracic Surgery | Year: 2013

Purpose: Transcatheter mitral valve replacement would represent a major advance in heart valve therapy. Such a device requires a specialized anchoring and sealing technology. This study was designed to test the feasibility of a novel mitral valve replacement device (the sutureless mitral valve [SMV]) designed to anchor and seal in the mitral position without need for sutures. Description: The SMV is a self-expanding device consisting of a custom-designed nitinol framework and a pericardial leaflet valve mechanism. Evaluation: Ten sheep underwent successful surgical SMV device implantation. All animals underwent cardiac catheterization 6 hours postoperatively. Hemodynamic, angiographic, echocardiographic and necroscopic data were recorded. The mean aortic cross-clamp time was 9.5 ± 3.1 minutes. Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Necropsy demonstrated that the SMV devices were anchored securely. Conclusions: This study demonstrates the feasibility and short-term success of sutureless mitral valve replacement using a novel SMV device. © 2013 The Society of Thoracic Surgeons.


Mahmood F.,Beth Israel Deaconess Medical Center | Kim H.,Beth Israel Deaconess Medical Center | Chaudary B.,Beth Israel Deaconess Medical Center | Bergman R.,Beth Israel Deaconess Medical Center | And 6 more authors.
Journal of Cardiothoracic and Vascular Anesthesia | Year: 2013

Objective: To demonstrate the clinical feasibility of accurately measuring tricuspid annular area by 3-dimensional (3D) transesophageal echocardiography (TEE) and to assess the geometric differences based on the presence of tricuspid regurgitation (TR). Also, the shape of the tricuspid annulus was compared with previous descriptions in the literature. Design: Prospective. Setting: Tertiary care university hospital. Interventions: Three-dimensional TEE. Participants: Patients undergoing cardiac surgery. Measurements and Main Results: Volumetric data sets from 20 patients were acquired by 3D TEE and prospectively analyzed. Comparisons in annular geometry were made between groups based on the presence of TR. The QLab (Philips Medical Systems, Andover, MA) software package was used to calculate tricuspid annular area by both linear elliptical dimensions and planimetry. Further analyses were performed in the 4D Cardio-View (TomTec Corporation GmBH, Munich, Germany) and MATLAB (Natick, MA) software environments to accurately assess annular shape. It was found that patients with greater TR had an eccentrically dilated annulus with a larger annular area. Also, the area as measured by the linear ellipse method was overestimated as compared to the planimetry method. Furthermore, the irregular saddle-shaped geometry of the tricuspid annulus was confirmed through the mathematic model developed by the authors. Conclusions: Three-dimensional TEE can be used to measure the tricuspid annular area in a clinically feasible fashion, with an eccentric dilation seen in patients with TR. The tricuspid annulus shape is complex, with annular high and low points, and annular area calculation based on linear measurements significantly overestimates 3D planimetered area. © 2013 Elsevier Inc.

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