Effect of Edge-to-Edge Mitral Valve Repair on Chordal Strain: Fluid-Structure Interaction Simulations.

Edge-to-edge repair for mitral valve regurgitation is being increasingly performed in high-surgical risk patients using minimally invasive mitral clipping devices. Known procedural complications include chordal rupture and mitral leaflet perforation. Hence, it is important to quantitatively evaluate the effect of edge-to-edge repair on chordal integrity. in this study, we employ a computational mitral valve model to simulate functional mitral regurgitation (FMR) by creating papillary muscle displacement. Edge-to-edge repair is then modeled by simulated coaptation of the mid portion of the mitral leaflets. in the setting of simulated FMR, edge-to-edge repair was shown to sustain low regurgitant orifice area, until a two fold increase in the inter-papillary muscle distance as compared to the normal mitral valve. Strain in the chordae was evaluated near the papillary muscles and the leaflets. Following edge-to-edge repair, strain near the papillary muscles did not significantly change relative to the unrepaired valve, while strain near the leaflets increased significantly relative to the unrepaired valve. These data demonstrate the potential for computational simulations to aid in the pre-procedural evaluation of possible complications such as chordal rupture and leaflet perforation following percutaneous edge-to-edge repair.

Multivariable prediction of renal insufficiency developing after cardiac surgery.

BACKGROUND: Renal insufficiency after coronary artery bypass graft (CABG) surgery is associated with increased short-term and long-term mortality. We hypothesized that preoperative patient characteristics could be used to predict the patient-specific risk of developing postoperative renal insufficiency. METHODS AND RESULTS: Data were prospectively collected on 11,301 patients in northern New England who underwent isolated CABG surgery between 2001 and 2005. Based on National Kidney Foundation definitions, moderate renal insufficiency was defined as a GFR <60 mL/min/1.73 m2 and severe renal insufficiency as a GFR <30. Patients with at least moderate renal insufficiency at baseline were eliminated from the analysis, leaving 8363 patients who became our study cohort. A prediction model was developed to identify variables that best predicted the risk of developing severe renal insufficiency using multiple logistic regression, and the predictive ability of the model quantified using a bootstrap validated C-Index (Area Under ROC) and Hosmer-Lemeshow statistic. Three percent of the patients with normal renal function before CABG surgery developed severe renal insufficiency (229/8363). In a multivariable model the preoperative patient characteristics most strongly associated with postoperative severe renal insufficiency included: age, gender, white blood cell count >12,000, prior CABG, congestive heart failure, peripheral vascular disease, diabetes, hypertension, and preoperative intraaortic balloon pump. The predictive model was significant with chi2 150.8, probability value <0.0001. The model discriminated well, ROC 0.72 (95%CI: 0.68 to 0.75). The model was well calibrated according to the Hosmer-Lemeshow test. CONCLUSIONS: We developed a robust prediction rule to assist clinicians in identifying patients with normal, or near normal, preoperative renal function who are at high risk of developing severe renal insufficiency. Physicians may be able to take steps to limit this adverse outcome and its associated increase in morbidity and mortality.

Perioperative increases in serum creatinine are predictive of increased 90-day mortality after coronary artery bypass graft surgery.

BACKGROUND: Impaired renal function after coronary artery bypass graft (CABG) surgery is a key risk factor for in-hospital mortality. However, perioperative increases in serum creatinine and the association with mortality has not been well-studied. We assessed the hypothesis that perioperative increases in creatinine are associated with increased 90-day mortality. METHODS AND RESULTS: We studied 1391 patients in northern New England undergoing CABG in 2001 and evaluated preoperative and postoperative creatinine. Patients with preoperative dialysis were excluded. Data were linked to the National Death Index to assess 90-day survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by percent increase in creatinine from baseline: <25%, 25% to 49%, 50% to 99%, > or =100%. We assessed 90-day survival and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for creatinine groups, adjusting for age and sex. Patients with the largest creatinine increases (50% to 99% or > or =100%) had significantly higher 90-day mortality compared with patients with a smaller increase (<50%; P<0.001). Adjusted HR and 95% CI confirmed patients in the higher 2 groups had an increased risk of mortality compared with the <25% (referent); however, the 25% to 49% group was not different from the referent: 1.80 (95% CI: 0.73 to 4.44), 6.57 (95% CI, 3.03 to 14.27), and 22.10 (95% CI, 11.25 to 43.39). CONCLUSIONS: Patients with large creatinine increases (> or = 50%) after CABG surgery have a higher 90-day mortality compared with patients with small increases. Efforts to identify patients with impaired renal function and to preserve renal function before cardiac surgery may yield benefits for patients in the future.

Fluid-structure interaction and structural analyses using a comprehensive mitral valve model with 3D chordal structure.

Over the years, three-dimensional models of the mitral valve have generally been organized around a simplified anatomy. Leaflets have been typically modeled as membranes, tethered to discrete chordae typically modeled as one-dimensional, non-linear cables. Yet, recent, high-resolution medical images have revealed that there is no clear boundary between the chordae and the leaflets. In fact, the mitral valve has been revealed to be more of a webbed structure whose architecture is continuous with the chordae and their extensions into the leaflets. Such detailed images can serve as the basis of anatomically accurate, subject-specific models, wherein the entire valve is modeled with solid elements that more faithfully represent the chordae, the leaflets, and the transition between the two. These models have the potential to enhance our understanding of mitral valve mechanics and to re-examine the role of the mitral valve chordae, which heretofore have been considered to be 'invisible' to the fluid and to be of secondary importance to the leaflets. However, these new models also require a rethinking of modeling assumptions. In this study, we examine the conventional practice of loading the leaflets only and not the chordae in order to study the structural response of the mitral valve apparatus. Specifically, we demonstrate that fully resolved 3D models of the mitral valve require a fluid-structure interaction analysis to correctly load the valve even in the case of quasi-static mechanics. While a fluid-structure interaction mode is still more computationally expensive than a structural-only model, we also show that advances in GPU computing have made such models tractable. Copyright © 2016 John Wiley & Sons, Ltd.

Fluid-Structure Interaction Analysis of Ruptured Mitral Chordae Tendineae.

The chordal structure is a part of mitral valve geometry that has been commonly neglected or simplified in computational modeling due to its complexity. However, these simplifications cannot be used when investigating the roles of individual chordae tendineae in mitral valve closure. For the first time, advancements in imaging, computational techniques, and hardware technology make it possible to create models of the mitral valve without simplifications to its complex geometry, and to quickly run validated computer simulations that more realistically capture its function. Such simulations can then be used for a detailed analysis of chordae-related diseases. In this work, a comprehensive model of a subject-specific mitral valve with detailed chordal structure is used to analyze the distinct role played by individual chordae in closure of the mitral valve leaflets. Mitral closure was simulated for 51 possible chordal rupture points. Resultant regurgitant orifice area and strain change in the chordae at the papillary muscle tips were then calculated to examine the role of each ruptured chorda in the mitral valve closure. For certain subclassifications of chordae, regurgitant orifice area was found to trend positively with ruptured chordal diameter, and strain changes correlated negatively with regurgitant orifice area. Further advancements in clinical imaging modalities, coupled with the next generation of computational techniques will enable more physiologically realistic simulations.

Fluid-Structure Interaction Analysis of Papillary Muscle Forces Using a Comprehensive Mitral Valve Model with 3D Chordal Structure.

Numerical models of native heart valves are being used to study valve biomechanics to aid design and development of repair procedures and replacement devices. These models have evolved from simple two-dimensional approximations to complex three-dimensional, fully coupled fluid-structure interaction (FSI) systems. Such simulations are useful for predicting the mechanical and hemodynamic loading on implanted valve devices. A current challenge for improving the accuracy of these predictions is choosing and implementing modeling boundary conditions. In order to address this challenge, we are utilizing an advanced in vitro system to validate FSI conditions for the mitral valve system. Explanted ovine mitral valves were mounted in an in vitro setup, and structural data for the mitral valve was acquired with [Formula: see text]CT. Experimental data from the in vitro ovine mitral valve system were used to validate the computational model. As the valve closes, the hemodynamic data, high speed leaflet dynamics, and force vectors from the in vitro system were compared to the results of the FSI simulation computational model. The total force of 2.6 N per papillary muscle is matched by the computational model. In vitro and in vivo force measurements enable validating and adjusting material parameters to improve the accuracy of computational models. The simulations can then be used to answer questions that are otherwise not possible to investigate experimentally. This work is important to maximize the validity of computational models of not just the mitral valve, but any biomechanical aspect using computational simulation in designing medical devices.

High-resolution subject-specific mitral valve imaging and modeling: experimental and computational methods.

The diversity of mitral valve (MV) geometries and multitude of surgical options for correction of MV diseases necessitates the use of computational modeling. Numerical simulations of the MV would allow surgeons and engineers to evaluate repairs, devices, procedures, and concepts before performing them and before moving on to more costly testing modalities. Constructing, tuning, and validating these models rely upon extensive in vitro characterization of valve structure, function, and response to change due to diseases. Micro-computed tomography ([Formula: see text]CT) allows for unmatched spatial resolution for soft tissue imaging. However, it is still technically challenging to obtain an accurate geometry of the diastolic MV. We discuss here the development of a novel technique for treating MV specimens with glutaraldehyde fixative in order to minimize geometric distortions in preparation for [Formula: see text]CT scanning. The technique provides a resulting MV geometry which is significantly more detailed in chordal structure, accurate in leaflet shape, and closer to its physiological diastolic geometry. In this paper, computational fluid-structure interaction (FSI) simulations are used to show the importance of more detailed subject-specific MV geometry with 3D chordal structure to simulate a proper closure validated against [Formula: see text]CT images of the closed valve. Two computational models, before and after use of the aforementioned technique, are used to simulate closure of the MV.

Non-linear fluid-coupled computational model of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: The dynamics of the mitral valve result from the synergy of left heart geometry, local blood flow and tissue integrity. Herein is presented the first coupled fluid-structure computational model of the mitral valve in which valvular kinematics result from the interaction of local blood flow and a continuum representation of valvular microstructure. METHODS: The diastolic geometry of the mitral valve was assembled from previously published experimental data. Anterior and posterior leaflets were modeled as networks of entangled collagen fibers, embedded in an isotropic matrix. The resulting non-linear continuum description of mitral tissue was implemented in a three-dimensional membrane formulation. Chordal tension-only behavior was defined from experimental tensile tests. The computational model considered the valve immersed in a domain of Newtonian blood, with an experimentally determined viscosity corresponding to a shear rate of 180 s(-1) at 37 degrees C. Ventricular and atrial pressure curves were applied to ventricular and atrial surfaces of the blood domain. RESULTS: Peak closing flow and volume were 51 ml/s and 1.17 ml, respectively. Papillary muscle force ranged dynamically between 0.0 and 2.6 N. Acoustic pressure (RMS) was found to be 3.3 Pa, with a peak frequency of 72 Hz at 0.064 s from the onset of systole. Model predictions showed excellent agreement with available transmitral flow, papillary force and first heart sound (S1) acoustic data. CONCLUSION: The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent a significant advance in computational studies of the mitral valve. This model will be the foundation for future computational studies on the effect of pathophysiological tissue alterations on mitral valve competence.

Potassium supplementation, diet vs pills: a randomized trial in postoperative cardiac surgery patients.

BACKGROUND: Cardiac surgery patients are commonly treated with diuretics, which can result in hypokalemia requiring potassium supplementation. OBJECTIVE: Our objective was to determine whether cardiac surgery patients receiving therapy with potassium-wasting diuretics can safely and beneficially maintain serum potassium levels by eating potassium-rich foods. DESIGN: A prospectively randomized trial of diet vs medication supplementation of potassium was undertaken. Patients who were to undergo cardiac surgery and who would be receiving therapy with oral furosemide postoperatively were eligible for the study. Forty-eight patients were enrolled in the trial, and 38 patients completed the study. Patients received either potassium-rich foods (diet) or potassium chloride pills (medication). RESULTS: There was no significant difference in mean (+/- SD) serum potassium concentrations between groups preoperatively (4.25 +/- 0.30 vs 4.29 +/- 0.33 mEq/L, respectively), on postoperative day 3 (4.23 +/- 0.40 vs 4.27 +/- 0.40 mEq/L, respectively), or postoperative day 4 (4.23 +/- 0.48 vs 4.24 +/- 0.33 mEq/L, respectively) for the diet and medication groups. Length of stay was significantly lower in the diet group (5.0 +/- 0.9 vs 6.3 +/- 2.2 days, respectively). When asked their preferences for method of supplementation, 79% of patients preferred the diet method. CONCLUSIONS: Cardiac surgery patients receiving therapy with diuretics can maintain serum potassium levels at clinically adequate concentrations by eating potassium-rich foods. Length of stay was significantly reduced. This method of potassium supplementation demonstrates the potential for reduced costs and increased patient satisfaction.

Ambulatory intraaortic balloon pump use as bridge to heart transplant.

BACKGROUND: This study evaluates a modification of an ambulatory intraaortic balloon pump (IABP) technique used in patients with heart failure of ischemic origin for bridge to transplant. METHODS: In this retrospective review we evaluated the ability to place the ambulatory IABP, any complications, time on device, and success in bridging to transplant on the ambulatory IABP device. In addition, the cost as compared to current ventricular assist devices was determined. RESULTS: Between July 2000 and November 2001, 4 patients have been managed with ambulatory IABP in our combined University of Wisconsin and William S. Middleton Veterans Administration programs. All 4 patients had ischemia as their mode of heart failure, and each had a relative contraindication to standard ventricular assist device use. All 4 patients had ambulatory IABPs successfully placed through the left axillary artery without complication, and were able to ambulate early after ambulatory IABP placement, and increased their rehabilitation status before transplantation. Ambulatory IABP support ranged from 12 to 70 days. All 4 patients have been successfully transplanted and discharged from the hospital. Use of the ambulatory IABP support, even with multiple replacements, translated to 10- to 50-fold savings for each of the reported patients versus standard ventricular assist device use. CONCLUSIONS: As a result of our initial experience, we believe that ambulatory IABP is an excellent mode of support in selected patients, and is cost-effective, as compared to conventional ventricular assist device therapy.

A coupled fluid-structure finite element model of the aortic valve and root.

BACKGROUND AND AIM OF THE STUDY: The study aim was to develop a three-dimensional coupled fluid-structure finite element model of the aortic valve and root. This model extends previous purely structural finite element models, and represents a significant step toward realistic simulation of the complex interactions among tissue material properties and valvular function. METHODS: The aortic root and valve geometry were extracted from magnetic resonance images and imported into the LS-Dyna explicit finite element package. Leaflet and root tissue were modeled with elastic material properties, and blood was modeled as a Newtonian liquid. A dynamic, fully unsteady analysis was performed in which blood flow through the valve was computed along with the motion of the leaflets and root in response to standard physiologic pressure wave profiles. RESULTS: The opening and closing of the aortic valve under physiological loading conditions was successfully simulated, and feasibility of the model illustrated. The motion of the simulated leaflets was consistent with that seen in intact hearts. Analysis of fluid flow patterns revealed eddy structures in the sinus regions and flow into the coronary circulation. CONCLUSION: The addition of blood flow to structural models of the aortic valve and root is a significant advance in modeling, and allows a closer simulation of valvular function. The model will be used to further assess normal and abnormal physiology as well as the effects of surgical intervention.

Biaxial mechanical properties of porcine ascending aortic wall tissue.

BACKGROUND AND AIM OF THE STUDY: Biaxial mechanical properties have been reported for porcine aortic valve leaflets, but not for the aortic root wall. These data are important for understanding the relationship between tissue material properties and function, providing a baseline for diseased tissue, and for providing a basis for numerical models of aortic mechanics. The study aim was to determine the biaxial material properties of porcine aortic root wall tissue. METHODS: Tissue samples (20 mm x 20 mm) were obtained from the aortic root walls of 18 pigs (anterior and posterior samples from each pig) and tested with a custom-built biaxial tensile testing apparatus. The data were fitted to the strain energy formulation: W = ?[a(long)E11(2) + a(circ)Ecc(2) + 2a(int)E11Ecc], where W is the strain energy, E11 = longitudinal strain, Ecc = circumferential strain, along, a(circ), and aint are the constants that were determined, and represent the longitudinal and circumferential elastic moduli, and interaction between the two axes, respectively. RESULTS: The root wall tissue was less stiff in the longitudinal direction (along = 115.8 +/- 8.4 kPa) than the circumferential direction (a(circ) = 169.9.3 +/- 7.4 kPa). As expected, there was mechanical interaction between the two axes (a(int) = 45.7 +/- 3.4 kPa). Additionally, anterior tissue samples were less stiff than posterior samples. All tissue samples exhibited a linear stress-strain relationship up to 40% strain, in contrast to aortic leaflet tissue, which was highly non-linear. CONCLUSION: These results demonstrated that the porcine aortic root wall tissue is an anisotropic material with linear elastic properties, in contrast to leaflet tissue. Additionally, the data suggest that a finite element model using an isotropic material as a basis for the aorta is insufficient for a physiologically accurate representation.

Quantitative Evaluation of Annuloplasty on Mitral Valve Chordae Tendineae Forces to Supplement Surgical Planning Model Development.

PURPOSE: Computational models of the heart's mitral valve (MV) exhibit potential for preoperative surgical planning in ischemic mitral regurgitation (IMR). However challenges exist in defining boundary conditions to accurately model the function and response of the chordae tendineae to both IMR and surgical annuloplasty repair. Towards this goal, a ground-truth data set was generated by quantifying the isolated effects of IMR and mitral annuloplasty on leaflet coaptation, regurgitation, and tethering forces of the anterior strut and posterior intermediary chordae tendineae. METHODS: MVs were excised from ovine hearts (N=15) and mounted in a pulsatile heart simulator which has been demonstrated to mimic the systolic MV geometry and coaptation of healthy and chronic IMR sheep. Strut and intermediary chordae from both MV leaflets (N=4) were instrumented with force transducers. Tested conditions included a healthy control, IMR, oversized annuloplasty, true-sized annuloplasty, and undersized mitral annuloplasty. A2-P2 leaflet coaptation length, regurgitation, and chordal tethering were quantified and statistically compared across experimental conditions. RESULTS: IMR was successfully simulated with significant increases in MR, tethering forces for each of the chordae, and decrease in leaflet coaptation (p<.05). Compared to the IMR condition, increasing levels of downsized annuloplasty significantly reduced regurgitation, increased coaptation, reduced posteromedial papillary muscle strut chordal forces, and reduced intermediary chordal forces from the anterolateral papillary muscle (p<.05). CONCLUSIONS: These results provide for the first time a novel comprehensive data set for refining the ability of computational MV models to simulate IMR and varying sizes of complete rigid ring annuloplasty.

Fluid-Structure Interactions of the Mitral Valve and Left Heart: Comprehensive Strategies, Past, Present and Future.

The remodeling that occurs after a posterolateral myocardial infarction can alter mitral valve function by creating conformational abnormalities in the mitral annulus and in the posteromedial papillary muscle, leading to mitral regurgitation (MR). It is generally assumed that this remodeling is caused by a volume load and is mediated by an increase in diastolic wall stress. Thus, mitral regurgitation can be both the cause and effect of an abnormal cardiac stress environment. Computational modeling of ischemic MR and its surgical correction is attractive because it enables an examination of whether a given intervention addresses the correction of regurgitation (fluid-flow) at the cost of abnormal tissue stress. This is significant because the negative effects of an increased wall stress due to the intervention will only be evident over time. However, a meaningful fluid-structure interaction model of the left heart is not trivial; it requires a careful characterization of the in-vivo cardiac geometry, tissue parameterization though inverse analysis, a robust coupled solver that handles collapsing Lagrangian interfaces, automatic grid-generation algorithms that are capable of accurately discretizing the cardiac geometry, innovations in image analysis, competent and efficient constitutive models and an understanding of the spatial organization of tissue microstructure. In this manuscript, we profile our work toward a comprehensive fluid-structure interaction model of the left heart by reviewing our early work, presenting our current work and laying out our future work in four broad categories: data collection, geometry, fluid-structure interaction and validation.

Long-term survival after cardiac surgery is predicted by estimated glomerular filtration rate.

BACKGROUND: Estimated glomerular filtration rate (eGFR) before coronary artery bypass graft (CABG) surgery is a key risk factor of in-hospital mortality. However, in patients with normal renal function before CABG, acute kidney injury develops after the procedure, making postoperative renal function assessment necessary for evaluation. Postoperative eGFR and its association with long-term survival have not been well studied. METHODS: We studied 13,593 consecutive CABG patients in northern New England from 2001 to 2006. Patients with preoperative dialysis were excluded. Data were linked to the Social Security Association Death Master File to assess long-term survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by established categories of postoperative eGFR (90 or greater, 60 to 89, 30 to 59, 15 to 29, and less than 15 mL x min(-1) x 1.73 m(-2)). RESULTS: Median follow-up was 2.8 years (mean, 2.7; range, 0 to 5.5). Patients with moderate to severe acute kidney injury (less than 60) after CABG had significantly worse survival than patients with little or no acute kidney injury (90 or greater). CONCLUSIONS: Patients having moderate to severe acute kidney injury after CABG surgery had worse 5-year survival compared with patients who had normal or near-normal renal function.

The relationship of normal and abnormal microstructural proliferation to the mitral valve closure sound.

BACKGROUND: Many diseases that affect the mitral valve are accompanied by the proliferation or degradation of tissue microstructure. The early acoustic detection of these changes may lead to the better management of mitral valve disease. In this study, we examine the nonstationary acoustic effects of perturbing material parameters that characterize mitral valve tissue in terms of its microstructural components. Specifically, we examine the influence of the volume fraction, stiffness and splay of collagen fibers as well as the stiffness of the nonlinear matrix in which they are embedded. METHODS AND RESULTS: To model the transient vibrations of the mitral valve apparatus bathed in a blood medium, we have constructed a dynamic nonlinear fluid-coupled finite element model of the valve leaflets and chordae tendinae. The material behavior for the leaflets is based on an experimentally derived structural constitutive equation. The gross movement and small-scale acoustic vibrations of the valvular structures result from the application of physiologic pressure loads. Material changes that preserved the anisotropy of the valve leaflets were found to preserve valvular function. By contrast, material changes that altered the anisotropy of the valve were found to profoundly alter valvular function. These changes were manifest in the acoustic signatures of the valve closure sounds. Abnormally, stiffened valves closed more slowly and were accompanied by lower peak frequencies. CONCLUSION: The relationship between stiffness and frequency, though never documented in a native mitral valve, has been an axiom of heart sounds research. We find that the relationship is more subtle and that increases in stiffness may lead to either increases or decreases in peak frequency depending on their relationship to valvular function.