Heart failure (HF) is a common cause of hospitalisation and mortality across industrialised countries. The number of hospitalisations and deaths attributed to heart failure is increasing, and this trend is predicted to continue. Numerical and in-vitro simulations of the human cardiovascular system constitute the basic tools for enhancing diagnostic and therapeutic technologies for HF and this would in turn, have significant effects on morbidity,mortality, and healthcare expenditure. Mechanical Circulatory Support (MCS) as a destination therapy for HF is rising significantly as it provides a cost-effective alternative to long-term treatment and cardiac transplantation. However, long-term versatility is far from ideal and incidence of transient and permanent neurological events is still high. To this end, evolution of MCS devices calls for more sophisticated design and evaluation methods. The purpose of this work is to develop a numerical model and to implemented a novel in-vitro model of the cardiovascular system with the intention of evaluating the performance characteristics of a purposely selected centrifugal pump impeller for the treatment of both Class III and IV HF conditions when placed in series with the heart at two different anatomic locations: Ascending Aorta and Descending Aorta. An existing lumped-parameter model of the CV system, that included models for the heart, the pulmonary and the systemic circulatory loops by adapting a modified version of the fourth-element Windkessel model was enhanced by dividing the systemic circulation into six parallel vascular beds, and by including an autoregulatory system to control both pressures and volumes throughout the system. As part of the novelty of the present work, a volume reflex loop was included with the purpose of simulating volume overload conditions, as commonly found in HF conditions, and obtaining a more realistic analysis of volume displacement, while using a MCS device. The in-vitro model implemented in this work adopted most of the features included in the mathematical counterpart with the purpose of validating the numerical results. As a result of the combination of models and proper optimisation of the system parameters, predictions of pathophysiological trends and MCS usage are satisfactorily obtained. The models implemented in this work offer a valuable tool for the selection and performance evaluation of MCS devices for the treatment of HF conditions.

Increasing numbers of old and sick patients who are no longer eligible for prolonged invasive implantation surgery have encouraged many researchers to investigate the development of a Mechanical Circulatory Support (MCS) device with more reliability and less possible invasive complications, which would benefit the majority of patients. This thesis will test experimentally and numerically the feasibility of installing an MCS device, as a bridge to destination, in the descending aorta, in a series configuration with the heart. To this end, a multi-chamber Simulator of the Cardio-Vascular blood-flow Loop (SCVL) was designed to simulate the in-vitro flow rates, pressures and other parameters representing normal and diseased conditions of the human cardiovascular system. The multi-chamber SCVL includes models for all four chambers of the heart, and the systemic as well as the pulmonic circulations. Next, a comprehensive study was conducted using the SCVL system to compare the novel in-series placement of the pump, in the descending aorta, with traditional in-parallel placements. Then, a comprehensive numerical study was conducted using the modified Concentrated Lumped Parameter (CLP) model developed by the same team. The numerical results are compared and verified by the experimental results under various conditions. The results for the pump installed in the descending aorta show that the pressure drop, upstream of the pump, facilitates the cardiac output as a result of after-load reduction. However, at the same time the generated pressure drop at the proximal part of the descending aorta induces a slight drop in the carotid perfusion which will be autoregulated by the brain in a native system. Further, the pressure rise downstream of the pump improves the blood perfusion in the renal artery. The pulse wave analysis show that the placement of the pump in the descending aorta leads to improved pulsatility which is beneficial for end-organ functionality in the native cardiovascular system.

Introduction: Heart failure remains a major public health problem, with recent estimates indicating that end-stage heart failure with two-year mortality rates of 70-80% affects over 60,000 patients in the US each year. Medical management can be used but success declines for patients with end stage heart failure. Although cardiac transplantation is optimal, less than 2500 cardiac transplants are performed annually due to the severely limited supply of donor organs. Mechanical circulatory support (MCS) devices are now routinely used to bridge patients with end-stage heart failure who become critically ill until a donor heart is available. The use of stem cell therapy to treat heart failure has been gaining significant ground in recent years, specifically due to its regenerative properties, and both animal and human models have shown significant improvements in ventricular mass, ejection fraction, vascularization, wall thickness, and infarct size reduction. Using the patients' HeartWare HVAD device diagnostics, we were able to acquire our response variable; pulsatility. Pulsatility is a variable measure of the differential between minimum and maximum flow and is dependent on device motor speed, power, current, and fluid viscosity. This measurement is important as it relates to the contractility of the heart and could potentially be used as an end point in determining when a patient is healthy enough to have their HVAD explanted. We set out to develop a low cost and effective predictive model to determine amniotic mesenchymal stem cell's ability to repair compromised cardiac tissue of patients using the Total Artificial Heart (TAH) and Donovan Mock Circulation Tank (DMC). Methods: Predictive modelling was performed using the TAH and DMC. The system was set to a range from critical heart failure to a normal operating conditions through the variation of preload, afterload, and ventricular drive pressures with the intent of comparing the results to our patient population. Patients (n=7, 3 dilated, 4 ischemic) received intravenous and intra-myocardial injections of a heterogeneous amniotic mesenchymal stem cells mixture and liquid matrix (MSCs+LM) at HVAD implant. Groups were analyzed based on treatment; control (HVAD only, n=7) versus stem cells (HVAD + MSCs+LM). HeartWare log files were acquired from patients' devices and analyzed in SAS and Matlab. Results from the patient study were compared to the predictive model to determine levels of stem cell response. Results: Pulsatility was found to increase with left drive pressure and afterload. Lower drive pressures resulted in a drop off in pulsatility at higher afterloads while higher drive pressures were able to compensate for any afterload. Pulsatility also increased with preload but lower drive pressures were unable to fully eject at the highest preloads, resulting in a reduced pulsatility. We observed the effects of the stem cell injections on pulsatility and found that patients receiving therapy demonstrated statistically significant increases in pulsatility at 15-20 (p=.0487), 25-30 (p=.0131), 35-40 (p=.0333), and 75-80 (p=0.0476) days post implant. At minimum, when comparing the patient results to the in vitro model, the therapy resulted in a progression from end stage HF conditions to medium cardiac function conditions. At maximum, the therapy resulted in a progression from end stage HF to normal healthy operating cardiac function. Conclusions: Stem cells demonstrated a significantly increased rate of change in pulsatility within the first 40 days and at 80 days post implant when compared to control. They also demonstrated progression from end stage HF to normal healthy cardiac function at two time periods (Days 40, 90). These results justify expansion of the study to encompass a larger patient population to verify the results of the in vitro model to predict cardiac regeneration with multiple functional status indicators.

The physiological and clinical considerations of centrifugal and axial pumps as ven- tricular assist devices (VADs) demands limitations on the power, size and geometry of the impellers. A typical pump design method is to rely on the characteristics of previously designed pumps with known performance using empirical equations and nondimensional parameters based on uid dynamics similarity law. Such data are widely available for industrial pumps operating in Reynolds number region of 108. VADs operate in Re < 106 and therefore the similarity concept does not apply between the industrial diagrams and the medical application of small pumps. The present dissertation employs a parametric approached analytical model to in- vestigate more than 150 axial and centrifugal pumps. The design parameters are optimised using the response surface methodology. The effect of different design parameters on the performance, force analysis and hemocompatibility of the pumps is thoroughly investigated by modelling the haemolysis through a power-law equation. The results show an explicit and consistent relationship between the number of blades, outlet width, outlet angle and the hemocompatibility of the device. Centrifu- gal pumps showed signi cantly lower probability of blood complications compared to axial pumps. The evaluation of the design characteristics helps pump designers to select their parameters accordingly for a low probability of blood complications. Furthermore, experimental techniques are employed to test more than 70 pumps in different conditions of flow, pressure and rotational speed. The experimental results validate the numerical simulations and create a database of empirical equations and data points for small axial and centrifugal pumps. The specifi c speed and speci fic diameters of the pumps are plotted on an ns − ds diagram to enable preliminary design of small pumps for VADs suitable for different stages of congestive heart failure (CHF).

The most recognized risk associated with the HeartMate II is thrombosis. In the presence of developing clot, the HeartMate II Display Monitor and System Controller senses a decrease in pump flow and is accompanied by audible and visual alarms when flow rates drop below a certain threshold; however, when flow is completely inhibited, the Display Monitor and System Controller both fail to indicate that flow has reduced to zero and does not produce any corresponding alarms. To test the efficacy of the HeartMate II alarms, the Donavan Mock was used to simulate the hemodynamics of a typical heart failure patient. The hemodynamics were then improved by the addition of the HeartMate II LVAS. Partially occluding the inflow and outflow of the HeartMate II did display changes in flow and presented with alarms when appropriate; however, complete occlusions of the device failed to produce any alarms or accurate changes in flow.

Class of 2015 Abstract / Objectives: To determine if using three-factor prothrombin complex concentrate (PCC) immediately prior to heart transplantation reduces blood product transfusions in patients bridged to heart transplantation by mechanical circulatory support (MCS) devices who are treated with warfarin. Methods: This study retrospectively reviewed patients that either received PCC or received usual care (i.e. fresh frozen plasma – FFP) prior to heart transplantation. Outcomes that were evaluated included packed red blood cell (RBC), FFP, platelet and cryoprecipitate transfusions intra and five days post-operatively, Cell Saver autologous blood volume administered intra-operatively, chest tube output for the five days post-operatively, and thromboembolic events post-operatively. Results: There were 24 patients included in the study, 12 from each group. The PCC group showed significantly less intra-operative RBC transfusion (2.60 ± 1.49 units vs. 5.09 ± 2.42 units, p=0.018), Cell Saver autologous blood usage (2.60 ± 1.49 units vs. 4.02 ± 1.55 units, p=0.032), and FFP transfusion (2.14 ± 2.30 units vs. 10.94 ± 5.96 units, p=0.0005) than the usual care group. There was no difference in amount of vitamin K given, change in INR, platelets administered, cryoprecipitate administered, chest tube output, or thromboembolic events between the groups. The average dose of PCC was 31 units/kg IV; repeat doses were given to 2 patients. Conclusions: We propose that the use of PCC prior to heart transplant surgery for patients on MCS devices anticoagulated with warfarin may result in the reduction for the need of RBC’s, autologous blood use and FFP during surgery.

Objectives: To analyze the use and prognostic impact of active mechanical circulatory support (MCS) devices in a large prospective contemporary cohort of patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Background: Although increasingly used in clinical practice, data on the efficacy and safety of active MCS devices in patients with CS complicating AMI are limited. Methods: This is a predefined subanalysis of the CULPRIT-SHOCK randomized trial and prospective registry. Patients with CS, AMI and multivessel coronary artery disease were categorized in two groups: (1) use of at least one active MCS device vs. (2) no active MCS or use of intra-aortic balloon pump (IABP) only. The primary endpoint was a composite of all-cause death or renal replacement therapy at 30 days. Results: Two hundred of 1055 (19%) patients received at least one active MCS device (n = 112 Impella®; n = 95 extracorporeal membrane oxygenation (ECMO); n = 6 other devices). The primary endpoint occurred significantly more often in patients treated with active MCS devices compared with those without active MCS devices (142 of 197, 72% vs. 374 of 827, 45%; p < 0.001). All-cause mortality and bleeding rates were significantly higher in the active MCS group (all p < 0.001). After multivariable adjustment, the use of active MCS was significantly associated with the primary endpoint (odds ratio (OR) 4.0, 95% confidence interval (CI) 2.7–5.9; p < 0.001). Conclusions: In the CULPRIT-SHOCK trial, active MCS devices were used in approximately one fifth of patients. Patients treated with active MCS devices showed worse outcome at 30 days and 1 year.

No description available.

Continuous-flow left ventricular assist devices provide mechanical circulatory assistance for patients suffering from end-stage heart failure that are awaiting or ineligible for heart transplantation. Although actuarial survival and quality of life with these devices is comparable to allograft transplant, they are associated with severe adverse events, including cerebrovascular accidents. Recent advances in continuous-flow technology aim to mitigate the risk of stroke by including design features that minimize flow stasis, turbulence and endothelial dysfunction, as well as promote near-normal pulse pressures. The proposed study is a multicenter, prospective, randomized clinical trial that aims to compare the stroke-free survival and associated incidence and risk of cerebrovascular accidents between three continuous-flow left ventricular assist devices in patients with refractory, end-stage heart failure planning to undergo bridge-to-transplant or destination therapy. Patients will be randomized to receive one of three devices (HeartMate II, Thoratec Corporation, Pleasanton, CA; HeartWare HVAD, HeartWare International Inc., Framingham, MA; HeartMate III, Thoratec Corporation, Pleasanton, CA). Patients will be monitored for stroke-free survival and incidence of cerebrovascular accident for 24 months post-implantation. Investigators will compare stroke-free survival with Kaplan-Meier survival curves and log-rank testing; in addition, investigators will examine each device’s level of risk for causing a cerebrovascular accident with chi square and odds ratio analysis. The data from this study will be used to guide treatment paradigms, device assignment and future development of technologies that mitigate stroke risk in this high-risk population.

Heart failure (HF) affects an estimated 5.8 million Americans, accounting for near 250,000 deaths each year. With shortages in available donor hearts, mechanical circulatory support (MCS) has emerged as a life-saving treatment for advanced stage HF. With growth in MCS use, a clinical and developmental need has emerged for a standard characterization and evaluation platform that may be utilized for inter-device comparison and system training. The goal of this research was to harness SynCardia's total artificial heart (TAH) to meet this need. We first sought to characterize the TAH in modern physiological terms - i.e. hemodynamics and pressure-volume loops. We then developed a model of HF using the TAH and mock circulatory system operating in a reduced output mode. We demonstrated that MCS devices could be incorporated and evaluated within the HF model. Finally, we characterized the operational envelope of SynCardia's Freedom (portable), Driver operating against varying loading conditions. Our results describe the hemodynamic envelope of the TAH. Uniquely, the TAH was found not to operate with time-varying elastance, to be insensitive to variations in afterload up to at least 135 mmHg mean aortic pressure, and exhibit Starling-like behavior. After transitioning the setup to mimic heart failure conditions, left atrial pressure and left ventricular pressure were noted to be elevated, aortic flow was reduced, sensitivity to afterload was increased, and Starling-like behavior was blunted, consistent with human heart failure. The system was then configured to allow ready addition of ventricular assist devices, which upon placement in the flow circuit resulted in restoration of hemodynamics to normal. Lastly, we demonstrated that the Freedom Driver is capable of overcoming systolic pressures of 200 mmHg as an upper driving limit. Understanding the physiology and hemodynamics of MCS devices is vital for proper use, future device development, and operator training. Characterization of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared to the human heart. The use of the system as a heart failure model has the potential to serve as a valuable research and teaching tool to foster safe MCS device use.