Predictive modeling of the virtual Hemi-Fontan operation for second stage single ventricle palliation: Two patient-specific cases

Single ventricle hearts are congenital cardiovascular defects in which the heart has only one functional pumping chamber. The treatment for these conditions typically requires a three-staged operative process where Stage 1 is typically achieved by a shunt between the systemic and pulmonary arteries, and Stage 2 by connecting the superior venous return to the pulmonary circulation. Surgically, the Stage 2 circulation can be achieved through a procedure called the Hemi-Fontan, which reconstructs the right atrium and pulmonary artery to allow for an enlarged confluence with the superior vena cava. Based on pre-operative data obtained from two patients prior to Stage 2 surgery, we developed two patient-specific multi-scale computational models, each including the 3D geometrical model of the surgical junction constructed from magnetic resonance imaging, and a closed-loop systemic lumped-parameter network derived from clinical measurements. “Virtual” Hemi-Fontan surgery was performed on the 3D model with guidance from clinical surgeons, and a corresponding multi-scale simulation predicts the patient\u27s post-operative hemodynamic and physiologic conditions. For each patient, a post-operative active scenario with an increase in the heart rate (HR) and a decrease in the pulmonary and systemic vascular resistance (PVR and SVR) was also performed. Results between the baseline and this “active” state were compared to evaluate the hemodynamic and physiologic implications of changing conditions. Simulation results revealed a characteristic swirling vortex in the Hemi-Fontan in both patients, with flow hugging the wall along the SVC to Hemi-Fontan confluence. One patient model had higher levels of swirling, recirculation, and flow stagnation. However, in both models, the power loss within the surgical junction was less than 13% of the total power loss in the pulmonary circulation, and less than 2% of the total ventricular power. This implies little impact of the surgical junction geometry on the SVC pressure, cardiac output, and other systemic parameters. In contrast, varying HR, PVR, and SVR led to significant changes in theses clinically relevant global parameters. Adopting a work-flow of customized virtual planning of the Hemi-Fontan procedure with patient-specific data, this study demonstrates the ability of multi-scale modeling to reproduce patient specific flow conditions under differing physiological states. Results demonstrate that the same operation performed in two different patients can lead to different hemodynamic characteristics, and that modeling can be used to uncover physiologic changes associated with different clinical conditions

Integration of Clinical Data Collected at Different Times for Virtual Surgery in Single Ventricle Patients: A Case Study

International audienceNewborns with single ventricle physiology are usually palliated with a multi-staged procedure. When cardiovascular complications e.g., collateral vessel formation occur during the inter-stage periods, further treatments are required. An 8-month-old patient, who underwent second stage (i.e., bi-directional Glenn, BDG) surgery at 4 months, was diagnosed with a major veno-venous collateral vessel (VVC) which was endovascularly occluded to improve blood oxygen saturations. Few clinical data were collected at 8 months, whereas at 4 months a more detailed data set was available. The aim of this study is threefold: (i) to show how to build a patient-specific model describing the hemodynamics in the presence of VVC, using patient-specific clinical data collected at different times; (ii) to use this model to perform virtual VVC occlusion for quantitative hemodynamics prediction; and (iii) to compare predicted hemodynamics with post-operative measurements. The three-dimensional BDG geometry, resulting from the virtual surgery on the first stage model, was coupled with a lumped parameter model (LPM) of the 8-month patient's circulation. The latter was developed by scaling the 4-month LPM to account for changes in vascular impedances due to growth and adaptation. After virtual VVC closure, the model confirmed the 2 mmHg BDG pressure increase, as clinically observed, suggesting the importance of modeling vascular adaptation following the BDG procedure

Patient-specific parameter estimation in single-ventricle lumped circulation models under uncertainty

Computational models of cardiovascular physiology can inform clinical decision-making, providing a physically consistent framework to assess vascular pressures and flow distributions, and aiding in treatment planning. In particular, lumped parameter network (LPN) models that make an analogy to electrical circuits offer a fast and surprisingly realistic method to reproduce the circulatory physiology. The complexity of LPN models can vary significantly to account, for example, for cardiac and valve function, respiration, autoregulation, and time-dependent hemodynamics. More complex models provide insight into detailed physiological mechanisms, but their utility is maximized if one can quickly identify patient specific parameters. The clinical utility of LPN models with many parameters will be greatly enhanced by automated parameter identification, particularly if parameter tuning can match non-invasively obtained clinical data. We present a framework for automated tuning of 0D lumped model parameters to match clinical data. We demonstrate the utility of this framework through application to single ventricle pediatric patients with Norwood physiology. Through a combination of local identifiability, Bayesian estimation and maximum a posteriori simplex optimization, we show the ability to automatically determine physiologically consistent point estimates of the parameters and to quantify uncertainty induced by errors and assumptions in the collected clinical data. We show that multi-level estimation, that is, updating the parameter prior information through sub-model analysis, can lead to a significant reduction in the parameter marginal posterior variance. We first consider virtual patient conditions, with clinical targets generated through model solutions, and second application to a cohort of four single-ventricle patients with Norwood physiology. Copyright © 2016 John Wiley & Sons, Ltd

A coupled computational framework for multiscale modeling and optimization of single ventricle repair

Multiscale modeling provides a means to relate global response to local changes in geometry and hemodynamics in the circulatory system. In this work, we couple a customized lumped parameter network (LPN) representing the whole circulation (heart, systemic and pulmonary circulations) to three-dimensional finite element models of two stages of the single ventricle surgical pathway. A fully-coupled closed-loop approach is employed using custom codes with Neumann boundary conditions at the inlets and outlets. The methodology is described, and applied to two stages of single ventricle repair to illustrate its utility: the BT-shunt (stage 1), and the Fontan surgery (stage 3).</jats:p

Integration of Clinical Data Collected at Different Times for Virtual Surgery in Single Ventricle Patients: A Case Study

Newborns with single ventricle physiology are usually palliated with a multi-staged procedure. When cardiovascular complications e.g., collateral vessel formation occur during the inter-stage periods, further treatments are required. An 8-month-old patient, who underwent second stage (i.e., bi-directional Glenn, BDG) surgery at 4 months, was diagnosed with a major veno-venous collateral vessel (VVC) which was endovascularly occluded to improve blood oxygen saturations. Few clinical data were collected at 8 months, whereas at 4 months a more detailed data set was available. The aim of this study is threefold: (i) to show how to build a patient-specific model describing the hemodynamics in the presence of VVC, using patient-specific clinical data collected at different times; (ii) to use this model to perform virtual VVC occlusion for quantitative hemodynamics prediction; and (iii) to compare predicted hemodynamics with post-operative measurements. The three-dimensional BDG geometry, resulting from the virtual surgery on the first stage model, was coupled with a lumped parameter model (LPM) of the 8-month patient's circulation. The latter was developed by scaling the 4-month LPM to account for changes in vascular impedances due to growth and adaptation. After virtual VVC closure, the model confirmed the 2 mmHg BDG pressure increase, as clinically observed, suggesting the importance of modeling vascular adaptation following the BDG procedure

From Patient-Specific Data to Multiscale Hemodynamics Simulations: the Challenge of Boundary Conditions

International audienceComputer fluid dynamics is now a common tool to explore hemodynamics in patient- specific simulations, either to better understand a specific physiopathology, explore several physiological states or to create a representative hemodynamics model preoperatively to explore several virtual surgical options. In this context, the specification of boundary conditions is key because pressure and flow within the modeled domain are driven by the interplay between geometry (form) and hemodynamics boundary conditions (function). However, these boundary conditions are rarely the measured variables. We thus show how one can go from patient-specific clinical data (MRI and catheterization) to simulation input parameters, including modeling assumptions and the impact of both on simulation results. To take into account the rest of the circulation outside of the three-dimensional modeled domain, a number of reduced order models exist. We explain how Windkessel models and more involved lumped parameter models can be calibrated, and discuss their predictive aspects. The specification of boundary conditions in patient-specific simulations can also create numerical challenges for which recent developments are explained. Applications include preoperative modeling and virtual surgical options in the Fontan palliation of single ventricle congenital heart disease, under rest and exercise

Respiratory effects on hemodynamics in patient-specific CFD models of the Fontan circulation under exercise conditions

Single ventricle malformations are complex congenital heart defects which require a three-stage surgical treatment, starting from the very first days of life, to separate the systemic and pulmonary circulations, and restore the serial circuit occurring in normal patients. The final surgery results in a total cavopulmonary connection (TCPC), where both the superior and the inferior vena cava are connected to the right pulmonary artery. Several clinical and computational studies have been done to optimize the geometry of the TCPC, with the aim of minimizing energy losses and improving surgical outcomes. To date, only few modeling studies have taken into account respiration and exercise as important factors to quantify the performance of a Fontan geometry. The objective of this work is to test the dependence of fluid dynamic variables and energy efficiency on respiration in patient-specific models of Fontan circulation, when subjected to exercise tests. A closed-loop multiscale approach was used, including a simple respiration model that modulates the extravascular pressures in the thoracic and abdominal cavities, to generate physiologic time-varying flow conditions. A lumped parameter network (LPN) representing the whole circulation was coupled to a patient-specific 3D finite volume model of the preoperative bidirectional cavo-pulmonary anastomosis (BCPA) with detailed pulmonary anatomy. Subsequently, three virtual TCPC alternatives were coupled to the LPN and investigated in terms of both local and global hemodynamics. In particular, a T-junction of the venae cavae to the pulmonary arteries, a design with an offset between the venae cavae and a Y-graft design were compared under exercise conditions. Results showed that the BCPA model is able to realistically capture oscillations due to both cardiac and respiratory effects, when compared to the venous Doppler velocity tracings acquired preoperatively on the patient. The differences in hemodynamics between the three investigated TCPC options were minimal and similar to those obtained without inclusion of respiratory effects. Hence, the three surgical options result to be equivalent according to the analyzed parameters. Moreover, although the simulation of the Fontan circulation with a respiratory model requires a longer computational time, the developed framework allows for a more physiologic method to incorporate respiratory effects that was not possible using other methods

From patient-specific data to multiscale hemodynamics simulations: the challenge of boundary conditions.

Computer fluid dynamics is now a common tool to explore hemodynamics in patientspecific simulations, either to better understand a specific physiopathology, explore several physiological states or to create a representative hemodynamics model preoperatively to explore several virtual surgical options. In this context, the specification of boundary conditions is key because pressure and flow within the modeled domain are driven by the interplay between geometry (form) and hemodynamics boundary conditions (function). However, these boundary conditions are rarely the measured variables. We thus show how one can go from patient-specific clinical data (MRI and catheterization) to simulation input parameters, including modeling assumptions and the impact of both on simulation results. To take into account the rest of the circulation outside of the three-dimensional modeled domain, a number of reduced order models exist. We explain how Windkessel models and more involved lumped parameter models can be calibrated, and discuss their predictive aspects. The specification of boundary conditions in patient-specific simulations can also create numerical challenges for which recent developments are explained. Applications include preoperative modeling and virtual surgical options in the Fontan palliation of single ventricle congenital heart disease, under rest and exercise

A Disseminated Mycobacterium Abscessus Infection in a Patient Affected by Pulmonary Graft versus Host Disease: Case Report with a Revision of Literature

Mycobacterium abscessus complex, hereinafter Mab, is a taxonomic group of rapidly growing, nontuberculous mycobacteria (NTM). Despite major advances in understanding virulence, pathogenicity and mechanism of antibiotic resistance, Mab remains a significant cause of pulmonary and extra-pulmonary disease. Herein, we describe a disseminated, macrolide-resistant, Mab subspecies abscessus infection occurring in a severely immune-compromised 34-year-old allotransplanted female patient affected by pulmonary chronic graft versus host disease (cGVHD). The infection was characterized by hematogenous spread, and besides lungs, it involved skin, and soft tissues, resulting in a highly debilitating, painful, and finally fatal disease. Our case describes the severe impact of Mab infections in the setting of allogeneic hematopoietic stem cells transplant (alloHSCT) and related complications. It also highlights the unmet need of preventive and surveillance measures together with the urgency of developing effective vaccines and drugs against emerging NTM. The scarce literature regarding Mab infections in alloHSCT patients is also reviewed

Virtual surgeries in patients with congenital heart disease: a multi-scale modelling test case.

International audienceThe objective of this work is to perform a virtual planning of surgical repairs in patients with congenital heart diseases--to test the predictive capability of a closed-loop multi-scale model. As a first step, we reproduced the pre-operative state of a specific patient with a univentricular circulation and a bidirectional cavopulmonary anastomosis (BCPA), starting from the patient's clinical data. Namely, by adopting a closed-loop multi-scale approach, the boundary conditions at the inlet and outlet sections of the three-dimensional model were automatically calculated by a lumped parameter network. Successively, we simulated three alternative surgical designs of the total cavopulmonary connection (TCPC). In particular, a T-junction of the venae cavae to the pulmonary arteries (T-TCPC), a design with an offset between the venae cavae (O-TCPC) and a Y-graft design (Y-TCPC) were compared. A multi-scale closed-loop model consisting of a lumped parameter network representing the whole circulation and a patient-specific three-dimensional finite volume model of the BCPA with detailed pulmonary anatomy was built. The three TCPC alternatives were investigated in terms of energetics and haemodynamics. Effects of exercise were also investigated. Results showed that the pre-operative caval flows should not be used as boundary conditions in post-operative simulations owing to changes in the flow waveforms post-operatively. The multi-scale approach is a possible solution to overcome this incongruence. Power losses of the Y-TCPC were lower than all other TCPC models both at rest and under exercise conditions and it distributed the inferior vena cava flow evenly to both lungs. Further work is needed to correlate results from these simulations with clinical outcomes