In-Vitro and In-Silico Investigations of Alternative Surgical Techniques for Single Ventricular Disease

Single ventricle (SV) anomalies account for one-fourth of all cases of congenital Heart disease. The conventional second and third stage i.e. Comprehensive stage II and Fontan procedure of the existing three-staged surgical approach serving as a palliative treatment for this anomaly, entails multiple complications and achieves a survival rate of 50%. Hence, to reduce the morbidity and mortality rate associated with the second and third stages of the existing palliative procedure, the novel alternative techniques called “Hybrid Comprehensive Stage II” (HCSII), and a “Self-powered Fontan circulation” have been proposed. The goal of this research is to conduct in-vitro investigations to validate computational and clinical findings on these proposed novel surgical techniques. The research involves the development of a benchtop study of HCSII and self-powered Fontan circulation

Computational fluid dynamics models and congenital heart diseases

Mathematical modeling is a powerful tool to investigate hemodynamics of the circulatory system. With improving imaging techniques and detailed clinical investigations, it is now possible to construct patient-specific models of reconstructive surgeries for the treatment of congenital heart diseases. These models can help clinicians to better understand the hemodynamic behavior of different surgical options for a treated patient. This review outlines recent advances in mathematical modeling in congenital heart diseases, the discoveries and limitations these models present, and future directions that are on the horizon

Computational fluid dynamics models and congenital heart diseases

Mathematical modeling is a powerful tool to investigate hemodynamics of the circulatory system. With improving imaging techniques and detailed clinical investigations, it is now possible to construct patient-specific models of reconstructive surgeries for the treatment of congenital heart diseases. These models can help clinicians to better understand the hemodynamic behavior of different surgical options for a treated patient. This review outlines recent advances in mathematical modeling in congenital heart diseases, the discoveries and limitations these models present, and future directions that are on the horizon

Computational Fluid Dynamics Investigation of A Novel Hybrid Comprehensive Stage II Operation For Single Ventricle Palliation

Hypoplastic left heart syndrome (HLHS) is a type of heart defect where the left ventricle is underdeveloped or not developed, resulting in only a single functioning right ventricle. Approximately 7.5% of patients with congenital heart disease are born with a single ventricle (SV) which is accompanied by a spectrum of other malformations such as atrophied ascending aorta, atrial septal defects, and ventricular septal defects (VSD). The existing three-hybrid staged surgical approach serving as a palliative treatment for this anomaly entails multiple complications and achieves a survival rate of only 50%. To reduce the trauma associated with the second stage of the hybrid procedure the hybrid comprehensive stage 2 (HCSII) operation can be a novel palliation alternative for a select subset of SV patients with adequate antegrade aortic flow. The procedure reduces surgical trauma in newborns by introducing a stented intrapulmonary baffle to avoid dissection of the pulmonary arteries and reconstruction of the aortic arch while obviating the dissection of the ductal continuation and distal arch. It is the purpose of this dissertation to undertake a computational investigation to elucidate the complex hemodynamics of patients who have undergone HCS II. This was accomplished in a multiscale manner coupling a 0D lumped parameter model (LPM) of the peripheral circulation with 3D pulsatile Computational Fluid Dynamics (CFD) model providing the details and enabling investigation of the HCS II complex hemodynamics. The use of CFD allows modeling of blood flow, the study of the effect of different surgical procedures, suggestion of potential improvements from investigation of areas of concern which are: the pressure drop across the baffle, the loading of the baffle itself, shear stress and shear rates that might lead to thrombus formation, as well as oxygen transport and particle residence time. A 3D anatomical model representative of a patient having undergone the HCSII was rendered utilizing the solid modeling software Solidworks based on anatomical landmarks from CT scans, and a 0D LPM was tuned to produce flowrates and waveforms that matched catheter data. The pulsatile CFD computations were carried out using the commercial STARCCM+ solver. Several cases of baffle strictures relevant to surgical implementations were considered and results showed that the largest pressure drop across the baffle reported was about 3 mmHg while for the same narrowing size and accounting for the distal arch kink, a four-fold increase is observed yielding a 12.15 mmHg drop. Moreover, the analysis showed that for averaged blood flow velocity of 0.5 m/s, no vortex shedding from the baffle was observed in the computational model due to the short distance from the baffle to the aortic arch apex. The velocity and pressure-flow fields were examined at different points throughout the cardia cycle: late diastole, early systole, peak systole, and early diastole. Reverse flow was observed towards late diastolic phase due to the presence of an adverse pressure gradient, and a stagnant flow in the aortic arch apex was also noticed. For the pulmonary circulation and due to the low flow velocity and low pulsatility, the T-junction shape of the SVC presented no risk of recirculation or swirling that may promote thrombogenesis. The wall shear stress on the baffle surface was also reported in pulsatile flow. It was observed that the flow detaches in systole and subsequently reattaches to the baffle surface. Moreover, the baffle surface experiences high wall shear stress magnitudes during systole and uneven distribution of WSS during diastole. The variation in the baffle related narrowing had a little impact on the flow hemodynamics, as shown by the nearly constant oxygen transport across the models. The geometrical modification applied to the models had little effect on the oxygen delivery for up to a 15% change between a 4 mm increment of MPA minimum diameter. The results showed consistency with the published data of Glenn patients. Particle residence time was also reported to identify any blood recirculation or flow stagnation that may lead to platelet activation leading to clot formation rate. On average particles take about 0.5(s) to exit the fluid domain. This time span is equal to the time of one cardiac cycle. Finally, the energy loss and energy efficiency were calculated as a function of split ratio and baffle related narrowing. Across all models, the efficiency was shown to be high

In Vitro Multi Scale Models to Study the Early Stage Circulations for Single Ventricle Heart Diseases Palliations

Single ventricle physiology can result from various congenital heart defects in which the patient has only one functional ventricle. Hypoplastic left heart syndrome refers to patients born with an underdeveloped left ventricle. A three stage palliation strategy is applied over the first several years of life to establish a viable circulation path using the one functioning ventricle. Results of the first stage Norwood procedure on neonates with hypoplastic left heart syndrome are unsatisfactory with high morbidities and mortalities primarily due to high ventricle load and other complications. An early second stage Bidirectional Glenn (BDG) procedure is not a suitable option for neonates due to their high pulmonary vascular resistance (PVR), which limits pulmonary blood flow. Realistic experimental models of these circulations are not well established and would be useful for studying the physiological response to surgical decisions on the distribution of flows to the various territories, so as to predict clinical hemodynamics and guide clinical planning. These would serve well to study novel intervention strategies and the effects of known complications at the local and systems-level. This study proved the hypothesis that it is possible to model accurately the first and second stage palliation circulations using multi-scale in vitro circulation models and to use these models to test novel surgical strategies while including the effects of possible complications. A multi-scale mock circulatory system (MCS), which couples a lumped parameter network model (LPN) of the neonatal circulation with an anatomically accurate three-dimensional model of the surgical anastomosis site, was built to simulate the hemodynamic performance of both the Stage 1 and Stage 2 circulations. A pediatric ventricular assist device was used as the single ventricle and a respiration model was applied to the Stage 2 circulation system. Resulting parameters measured were pressure and flow rates within the various territories, and systemic oxygen delivery (OD) were calculated. The Stage 1 and Stage 2 systems were validated by direct comparisons of time-based and mean pressures and flow rates between the experimental measurements, available clinical recordings and/or CFD simulations. Regression and correlation analyses and unpaired t-tests showed that there was excellent agreement between the clinical and experimental time-based results as measured throughout the circulations (0.60 \u3c R^2 \u3c 0.99; p \u3e 0.05, r.m.s error\u3c 5%). A novel, potentially alternative surgical strategy for the initial palliation, was proposed and was tested, called the assisted bidirectional Glenn (ABG) procedure. The approach taps the higher potential energy of the systemic circulation through a systemic to caval shunt with nozzle to increase pulmonary blood flow and oxygen delivery within a superior cavopulmonary connection. Experimental model was validated against a numerical model (0.65 \u3c sigma \u3c 0.97; p \u3e 0.05). The tested results demonstrated the ABG had two main advantages over the Norwood circulation. First, the flow through the ABG shunt is a fraction of the pulmonary flow, reducing the volume overload on the single ventricle and improving systemic and coronary perfusion. Second, the ABG should provide a more stable source of pulmonary flow, which should reduce thrombotic risk or intimal thickening over an mBT shunt. A study to examine the ejector pump effect was conducted. Two parameters were investigated: (1) the superior vena cava (SVC) and pulmonary artery (PA) pressure difference; and (2) the SVC and PA pressure difference relative to PA flow rate. Results validated the hypothesis that an ejector pump advantage can be adopted in a superior cavo-pulmonary circulation, where the low-energy pulmonary blood flow can be assisted by an additional source of high energy flow from the systemic circulation. But the ejector pump effect produced by the current nozzle designs was not strong. Parametric study includes nozzle size, placement, and nozzle shape was conducted. Results shown that nozzle to shunt diameter ratio had the most important effects on the ABG performance. As β increased, pulmonary artery flow rate and systemic oxygen delivery increased. A suggested β value falls between 0.48 and 0.72. The study showed that a bigger β produced a smaller resistance value. The shape of the nozzle did not change the resistance value. The effects of shunt angle, nozzle placement and nozzle shape on the ABG circulation were not statistical significant. The aortic coarctation study showed that the aortic coarctation could have an effect on the ABG circulation. The coarctation index (CoI) around 0.5 was found to be the transition point between no effects (CoI \u3e 0.5) and discernible effects on the ABG circulation. These effects include changes in pulmonary to systemic flow distribution. In summary, this research verified and validated an in vitro mock circulatory system (MCS) for Stage 1 and Stage 2 circulations. The system was used to assess a novel conceptual surgery option named the ABG. Parametric studies were conducted to give guidance on designing the important element for the ABG: the shunt (nozzle) connecting the SVC and systemic circulation. The performance of the ABG under one unhealthy condition, namely, aortic coarctation was assessed

Hypoplastic Left Heart Syndrome Current Considerations and Expectations

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients

Staged surgical palliation and ventricular performance in functionally single ventricle anatomy

This thesis reports a series of laboratory and clinical studies designed to investigate the acute effect of surgical palliation on ventricular function in children with functionally single ventricle anatomy. Ventricular volume and pressure were measured using a combined pressure-conductance catheter. Initial laboratory-based experiments were performed using a physical model of the left ventricle, which allowed examination of the measurement techniques used in the clinical studies but under controlled conditions. These experiments identified a non-linear conductance-absolute volume relationship and demonstrated for the first time that the calibration coefficient, $\alpha_{SV}$ produced a significant, volume-dependent measurement error. These experiments also demonstrated that conductance volume measurements were adversely influenced by other electrical signals. The ventricular electrogram produced clinically important measurement error that has not previously been described. Two clinical studies were then undertaken to investigate the separate effects of the bidirectional cavo-pulmonary anastomosis (BCPA) and the completion total cavo-pulmonary connection (TCPC). These studies represent the core of the thesis. Both procedures were associated with significant changes in the pressure and volume conditions of the dominant ventricle. In addition, the BCPA was associated with a substantial and immediate improvement in ventricular systolic function but this was accompanied by an increase in diastolic chamber stiffness. By contrast, the TCPC was not associated with a significant change ventricular systolic or diastolic function in spite of the changes in ventricular load. Comparable changes were observed in patients with a dominant ventricle of either left or right ventricular morphology. These studies provide a more detailed understanding about the acute events that accompany surgical palliation in children with functionally single ventricle anatomy. These findings confirm the validity of staged surgical palliation in the management of these children

IN VITRO MULTI-SCALE PATIENT-SPECIFIC MODELING OF HEMODYNAMICS IN STAGE 1 NORWOOD PALLIATION FOR THE TREATMENT OF SINGLE VENTRICLE HEART DISEASE

Hypoplastic left heart syndrome (HLHS) is a congenital heart defect in which the left ventricle is severely underdeveloped. The Norwood procedure is the first stage procedure to make an unrestrictive systemic blood flow and at the same time balance it with the pulmonary flow. This is done by constructing a neo-aorta using the pulmonary artery root and the autologous aorta, and then installing a shunt to the pulmonary artery. Variations of the Norwood surgery include the modified Blalock-Taussig (mBT) shunt, which diverts blood from the innominate artery to the pulmonary artery (PA), and the Right Ventricle Shunt (RVS), which diverts blood from the right ventricle to the PA. Recurrent neo-aortic coarctation (NAO) is a frequent complication of the Norwood procedure. It causes changes in circulation flow rate balances and hypertension in the aortic arch. Conventionally, the value of a coarctation index (CoI) is used in choosing interventions to treat NAO. Aortic arch morphology of Norwood patients is suspected to be a factor of hemodynamic response to NAO. This study aims to develop and validate an in vitro model of the Norwood circulation and to use it to better understand the hemodynamic impact of progressive coarctation severity in the Norwood patients with mBT and RVS shunts. Five patient-specific cases were selected, each case having a different aortic morphology. A multi-scale mock circulatory system (MCS) was developed to simulate patient-specific Norwood circulation. The MCS couples a lumped parameter network (LPN) model of the circulation with the 3D test section of the aorta and superior arteries. The system includes branches for the pulmonary, upper body, lower body and single ventricle. The MCS was set to patient specific conditions based on the clinical measurements. Flow rate and pressure measurements were made around the circulation model. The native arch anatomy of each patient was morphed to simulate coarctation by controlling the amount of narrowing of the aortic isthmus, while keeping the original patient-specific aortic geometry intact. Separate NAO models were created to provide for a range of CoI. Aortic pressure measurements were made to study pressure drop and recovery effects. In a further study, the MCS was modified to simulate the Norwood circulation with RVS. The NAO models were used to study coarctation effects. The MCS was validated against clinical measurements. The experimental measurements demonstrated that the time-based flow rate and pressure developed within the circulation recapitulated clinical measurements (0.72 \u3c R2 \u3c 0.95). The results showed good fidelity in replicating the mean values of the Norwood circulation at the patient-specific level (p \u3e 0.10). The system demonstrated the coarctation effects in the Norwood circulation with mBT. For all patient cases, the single ventricle power (SVP), mean pressure difference, and Qp/Qs increased noticeably when CoI \u3c 0.5 (p\u3c0.05). An increased SVP correlated with abnormal aortic arch morphology (dilated or tubular). Measurements from two of four cases studied showed that substituting the mBT with the RVS can relieve pulmonary overcirculation and improve the pulmonary to systemic flow balance (Qp/Qs). Using the RVS reduced SVP requirements by 74.5 mW on average. A tubular arch morphology was associated with a higher SVP with the RVS than those patients with a dilated arch. The study has shown that the hypothesis, “NAO may not need immediate surgical intervention at an early stage for some patients†was accepted. Aortic arch morphology does affect the hemodynamic response to NAO. Any morphological abnormality causes extra SVP. The RVS can relieve overcirculation and is associated with lower SVP level and SVP changes in some of the patients