Coupled thermal-hemodynamics computational modeling of cryoballoon ablation for pulmonary vein isolation.

Cryoballoon ablation (CBA) is a cryo-energy based minimally invasive treatment procedure for patients suffering from left atrial (LA) fibrillation. Although this technique has proved to be effective, it is prone to reoccurrences and some serious thermal complications. Also, the factors affecting thermal distribution at the pulmonary vein-antrum junction that are critical to the treatment success is poorly understood. Computer modeling of CBA can resolve this issue and help understand the factors affecting this treatment. To do so, however, numerical challenges associated with the simulation of advection-dominant transport process must be resolved. Here, we describe the development of a thermal-hemodynamics computational framework to simulate incomplete occlusion in a patient-specific LA geometry during CBA. The modeling framework uses the finite element method to predict hemodynamics, thermal distribution, and lesion formation during CBA. An incremental pressure correction scheme is used to decouple velocity and pressure in the Navier-Stokes equation, whereas several stabilization techniques are also applied to overcome numerical instabilities. The framework was implemented using an open-source FE library (FEniCS). We show that model predictions of the hemodynamics in a realistic human LA geometry match well with measurements. The effects of cryoballoon position, pulmonary vein blood velocity and mitral regurgitation on lesion formation during CBA was investigated. For a -700C cryoballoon temperature, the model predicts lesion formation for gaps less than 2.5 mm and increasing efficiency of CBA for higher balloon tissue contact areas. The simulations also predict that lesion formation is not sensitive to variation in pulmonary vein blood velocity and mitral regurgitation. The framework can be applied to optimize CBA in patients for future clinical studies.

Force-dependent recruitment from myosin OFF-state increases end-systolic pressure-volume relationship in left ventricle.

Finite element (FE) modeling is becoming increasingly prevalent in the world of cardiac mechanics; however, many existing FE models are phenomenological and thus do not capture cellular-level mechanics. This work implements a cellular-level contraction scheme into an existing nonlinear FE code to model ventricular contraction. Specifically, this contraction model incorporates three myosin states: OFF-, ON-, and an attached force-generating state. It has been speculated that force-dependent transitions from the OFF- to ON-state may contribute to length-dependent activation at the cellular level. The current work investigates the contribution of force-dependent recruitment out of the OFF-state to ventricular-level function, specifically the Frank-Starling relationship, as seen through the end-systolic pressure-volume relationship (ESPVR). Five FE models were constructed using geometries of rat left ventricles obtained via cardiac magnetic resonance imaging. FE simulations were conducted to optimize parameters for the cellular contraction model such that the differences between FE predicted ventricular pressures for the models and experimentally measured pressures were minimized. The models were further validated by comparing FE predicted end-systolic strain to experimentally measured strain. Simulations mimicking vena cava occlusion generated descending pressure volume loops from which ESPVRs were calculated. In simulations with the inclusion of the OFF-state, using a force-dependent transition to the ON-state, the ESPVR calculated was steeper than in simulations excluding the OFF-state. Furthermore, the ESPVR was also steeper when compared to models that included the OFF-state without a force-dependent transition. This suggests that the force-dependent recruitment of thick filament heads from the OFF-state at the cellular level contributes to the Frank-Starling relationship observed at the organ level.

Applications of computational modeling in cardiac surgery.

Although computational modeling is common in many areas of science and engineering, only recently have advances in experimental techniques and medical imaging allowed this tool to be applied in cardiac surgery. Despite its infancy in cardiac surgery, computational modeling has been useful in calculating the effects of clinical devices and surgical procedures. In this review, we present several examples that demonstrate the capabilities of computational cardiac modeling in cardiac surgery. Specifically, we demonstrate its ability to simulate surgery, predict myofiber stress and pump function, and quantify changes to regional myocardial material properties. In addition, issues that would need to be resolved in order for computational modeling to play a greater role in cardiac surgery are discussed.

Analysis of patient-specific surgical ventricular restoration: importance of an ellipsoidal left ventricular geometry for diastolic and systolic function.

Surgical ventricular restoration (SVR) is a procedure designed to treat heart failure by surgically excluding infarcted tissues from the dilated failing left ventricle. To elucidate and predict the effects of geometrical changes from SVR on cardiac function, we created patient-specific mathematical (finite-element) left ventricular models before and after surgery using untagged magnetic resonance images. Our results predict that the postsurgical improvement in systolic function was compromised by a decrease in diastolic distensibility in patients. These two conflicting effects typically manifested as a more depressed Starling relationship (stroke volume vs. end-diastolic pressure) after surgery. By simulating a restoration of the left ventricle back to its measured baseline sphericity, we show that both diastolic and systolic function improved. This result confirms that the increase in left ventricular sphericity commonly observed after SVR (endoventricular circular patch plasty) has a negative impact and contributes partly to the depressed Starling relationship. On the other hand, peak myofiber stress was reduced substantially (by 50%) after SVR, and the resultant left ventricular myofiber stress distribution became more uniform. This significant reduction in myofiber stress after SVR may help reduce adverse remodeling of the left ventricle. These results are consistent with the speculation proposed in the Surgical Treatment for Ischemic Heart Failure trial (20) for the neutral outcome, that "the lack of benefit seen with surgical ventricular reconstruction is that benefits anticipated from surgical reduction of left ventricular volume (reduced wall stress and improvement in systolic function) are counter-balanced by a reduction in diastolic distensibility."

Algisyl-LVR™ with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart.

BACKGROUND: Left ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™+CABG) on both LV function and wall stress in heart failure patients. METHODS AND RESULTS: Magnetic resonance images obtained before treatment (n=3), and at 3 months (n=3) and 6 months (n=2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264 ± 91 ml to 146 ± 86 ml and ESV decreased from 184 ± 85 ml to 86 ± 76 ml. Ejection fraction increased from 32 ± 8% to 47 ± 18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06 ± 0.21 cm (baseline) to 1.3 ± 0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV. CONCLUSIONS: These results support the novel concept that Algisyl-LVR™+CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function.

Patient-specific finite element-based analysis of ventricular myofiber stress after Coapsys: importance of residual stress.

BACKGROUND: We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc, Maple Grove, MN) implantation using a finite element model of the left ventricle (LV). Chronic ischemic mitral regurgitation is caused by LV remodeling after posterolateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases chronic ischemic mitral regurgitation. METHODS: Finite element models of the LV were based on magnetic resonance images obtained before (preoperatively) and after (postoperatively) coronary artery bypass grafting with Coapsys implantation in a single patient. To determine the effect of Coapsys and LV before stress, virtual Coapsys was performed on the preoperative model. Diastolic and systolic material variables in the preoperative, postoperative, and virtual Coapsys models were adjusted so that model LV volume agreed with magnetic resonance imaging data. Chronic ischemic mitral regurgitation was abolished in the postoperative models. In each case, myofiber stress and pump function were calculated. RESULTS: Both postoperative and virtual Coapsys models shifted end-systolic and end-diastolic pressure-volume relationships to the left. As a consequence and because chronic ischemic mitral regurgitation was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at end-diastole and end-systole in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV prestress was necessary for accurate calculation of LV myofiber stress, especially in the remote zone. CONCLUSIONS: Coapsys decreases myofiber stress at end-diastole and end-systole. The improvement in myofiber stress may contribute to the long-term effect of Coapsys on LV remodeling.

First evidence of depressed contractility in the border zone of a human myocardial infarction.

BACKGROUND: The temporal progression in extent and severity of regional myofiber contractile dysfunction in normally perfused border zone (BZ) myocardium adjacent to a myocardial infarction (MI) has been shown to be an important pathophysiologic feature of the adverse remodeling process in large animal models. We sought, for the first time, to document the presence of impaired contractility of the myofibers in the human BZ myocardium. METHODS: A 62-year-old man who experienced an MI in 1985 and had recently had complete revascularization was studied. Myofiber systolic contractile stress developed in the normally perfused BZ adjacent to the MI (T(max_B)) and that developed in regions remote from the MI (T(max_R)) were quantified using cardiac catheterization, magnetic resonance imaging, and mathematical modeling. RESULTS: The resulting finite element model of the patient's beating left ventricle was able to simulate the reduced systolic strains measured using magnetic resonance imaging at matching left ventricular pressures and volumes. The T(max_B) (73.1 kPa) was found to be greatly reduced relative to T(max_R) (109.5 kPa). These results were found to be independent of assumptions relating to BZ myofiber orientation. CONCLUSIONS: The results of this study document the presence of impaired contractility of the myofibers in the BZ myocardium and support its role in the post-MI remodeling process in patients. To fully establish this important conclusion serial evaluations beginning at the time of the index MI will need to be performed in a cohort of patients. The current study supports the importance and demonstrates the feasibility of larger and longer-term studies.