James F. Antaki

HeartMate II Left Ventricular Assist System: From Concept to First Clinical Use

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Computational simulation of platelet deposition and activation: I. Model development and properties.

AbstractTo better understand the mechanisms leading to the formation and growth of mural thrombi on biomaterials, we have developed a two-dimensional computational model of platelet deposition and activation in flowing blood. The basic formulation is derived from prior work by others, with additional levels of complexity added where appropriate. It is comprised of a series of convection-diffusion-reaction equations which simulate platelet-surface and platelet-platelet adhesion, platelet activation by a weighted linear combination of agonist concentrations, agonist release and synthesis by activated platelets, platelet-phospholipid-dependent thrombin generation, and thrombin inhibition by heparin. The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and resting and activated platelet-surface and platelet-platelet reaction rate constants. The model is formulated to simulate a wide range of biomaterials and complex flows. In this article we present the basic model and its properties; in Part II (Sorensen et al., Ann. Biomed. Eng. 27:449–458, 1999) we apply the model to experimental results for platelet deposition onto collagen.

Effects of turbulent stresses upon mechanical hemolysis: experimental and computational analysis.

Experimental and computational studies were performed to elucidate the role of turbulent stresses in mechanical blood damage (hemolysis). A suspension of bovine red blood cells (RBC) was driven through a closed circulating loop by a centrifugal pump. A small capillary tube (inner diameter 1 mm and length 70 mm) was incorporated into the circulating loop via tapered connectors. The suspension of RBCs was diluted with saline to achieve an asymptotic apparent viscosity of 2.0 ± 0.1 cP at 23°C to produce turbulent flow at nominal flow rate and pressure. To study laminar flow at the identical wall shear stresses in the same capillary tube, the apparent viscosity of the RBC suspension was increased to 6.3 ± 0.1 cP (at 23°C) by addition of Dextran-40. Using various combinations of driving pressure and Dextran mediated adjustments in dynamic viscosity Reynolds numbers ranging from 300–5,000 were generated, and rates of hemolysis were measured. Pilot studies were performed to verify that the suspension media did not affect mechanical fragility of the RBCs. The results of these bench studies demonstrated that, at the same wall shear stress in a capillary tube, the level of hemolysis was significantly greater (p < 0.05) for turbulent flow as compared with laminar flow. This confirmed that turbulent stresses contribute strongly to blood mechanical trauma. Numerical predictions of hemolysis obtained by computational fluid dynamic modeling were in good agreement with these experimental data.

Experience with univentricular support in mortally ill cardiac transplant candidates

Between July 1987 and March 1989, 11 patients underwent left ventricular support with the Novacor left ventricular assist system irrespective of apparent degree of right ventricular failure. The first 2 patients died of multisystem organ failure while on support. All the remaining patients survived the support period, and actuarial survival after transplantation was 100% at 6 months and 89% at 1 year. In no patient did bacterial infection develop during support or after transplantation. Right ventricular ejection fraction before implantation of the left ventricular assist system was lower than 15% in 6 of 8 patients, yet it increased twofold during left ventricular support. The need for excessive inotropic support (2 patients) or temporary (four days) mechanical right ventricular support (2 patients) while on the left ventricular support system appeared to be related to elevated pulmonary vascular resistance during support in association with large preimplantation ventricular volumes. It appears that even patients with compromised right ventricular performance can be supported long term with a left ventricular assist device. Patients with elevated pulmonary vascular resistance may require temporary right ventricular support.

Survival after biventricular assist device implantation: An analysis of the Interagency Registry for Mechanically Assisted Circulatory Support database

BACKGROUND Patients requiring biventricular assist device (BiVAD) for mechanical circulatory support (MCS) have substantially worse outcomes than patients requiring left VAD (LVAD) support only. Patient-specific risk factors have yet to be consistently identified in a large, multicenter registry, which may underlie the poorer outcomes for BiVAD patients. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a registry of U.S. Food and Drug Administration-approved durable MCS devices used for bridge-to-transplantation, destination therapy, or recovery. The purposes of this study were to 1) identify the underlying pre-implant characteristics of the population requiring BiVAD support that contribute to reduced survival, and 2) identify differences in postoperative outcomes with respect to adverse events compared with patients supported with LVAD alone. METHODS From June 2006 to September 2009, 1,646 patients were entered into the INTERMACS database in which adverse events and outcomes were recorded for primary implants with LVAD or BiVAD. Competing outcomes methodology was used to estimate the time-related probability of death, transplant, or recovery. Overall survival for all groups was analyzed with Kaplan-Meier methods and Cox proportional regression analysis. RESULTS The distribution of primary device implants included 1,440 LVADs and 206 BiVADs. BiVAD patients presented with a lower INTERMACS profile 93% in INTERMACS 1 or 2, compared with 73% for LVAD patients (p < 0.001). Survival at 6 months was 86% for LVADs and 56% for BiVADs (p < .0001). Adverse event rates, expressed as episodes/100 patient-months for the BiVAD group compared with LVAD, were significantly higher for infection (33.2 vs 14.3), bleeding (71.6 vs 15.5), neurologic events (7.9 vs 2.6), and for device failure (4.9 vs 2.0). CONCLUSIONS Patients requiring BiVAD support at the time of durable MCS implant are more critically ill at the time of MCS implant. BiVAD patients experience worse survival than patients supported with LVAD alone and higher rates of serious adverse events. Characteristics of the population present at the time of BiVAD implant likely influence post-implant MCS outcomes.

Computational Simulation of Platelet Deposition and Activation: II. Results for Poiseuille Flow over Collagen

AbstractWe have previously described the development of a two-dimensional computational model of platelet deposition onto biomaterials from flowing blood (Sorensen et al., Ann. Biomed. Eng. 27:436–448, 1999). The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and three platelet-deposition-related reaction rate constants. These parameters are estimated for platelet deposition onto a collagen substrate for simple parallel-plate flow of whole blood in both the presence and absence of thrombin. One set of experimental results is used as a benchmark for model-fitting purposes. The “trained” model is then validated by applying it to additional test cases from the literature for parallel-plate Poiseuille flow over collagen at both higher and lower wall shear rates, and in the presence of various anticoagulants. The predicted values agree very well with the experimental results for the training cases, and good reproduction of deposition trends and magnitudes is obtained for the heparin, but not the citrate, validation cases. The model is formulated to be easily extended to synthetic biomaterials, as well as to more complex flows.

A sensorless approach to control of a turbodynamic left ventricular assist system

A fuzzy logic controller for a rotary, turbodynamic left ventricular assist system was developed to optimize the delivery of blood flow without inducing suction in the ventricle. The controller is based on the pulsatility in blood flow through the pump and assumes that the natural heart is still able to produce some pumping action. To avoid the use of flow transducers, which are not reliable for long term use, the controller estimates flow using a model of the assist device. The controller was tested in computer simulation, a mock circulatory system, and in animal experiments. Simulation studies suggest that the fuzzy logic controller is more robust to parameter changes than a traditional proportional-integral controller. Experimental results in animals showed that the controller is able to provide satisfactory flows at adequate perfusion pressures while avoiding suction in the left ventricle.

Decrease in red blood cell deformability caused by hypothermia, hemodilution, and mechanical stress: Factors related to cardiopulmonary bypass

During extracorporeal circulation in cardiopulmonary bypass (CPB) surgery, blood is exposed to anomalous mechanical and environmental factors, such as high shear stress, turbulence, decreased oncotic pressure caused by dilution of plasma, and moderate and especially deep hypothermia widely applied during CPB in infants. These factors cause damage to the red blood cells (RBCs), which is manifest by immediate and delayed hemolysis and by changes in the mechanical properties of RBCs. These changes include, in particular, decrease in RBC deformability impeding the passage of RBCs through the microvessels and may contribute to the complications associated with CPB surgery. We investigated in vitro the independent and combined effects of hypothermia, plasma dilution, and mechanical stress on deformability of bovine RBCs. Our studies showed each of these factors to cause a significant decrease in the deformability of RBCs, especially acting synergistically. The impairment of RBC deformability caused by hypothermia was found to be more pronounced for RBCs suspended in phosphate buffered saline (PBS) than for RBCs suspended in plasma. The decrease in RBC deformability caused by mechanical stress was significantly exacerbated by dilution of plasma with PBS. In summary, results of our in vitro study strongly point to a possible detrimental consequence of conventional CPB arising from increased RBC rigidity, which may lead to impaired microcirculation and tissue oxygen supply.

Quantitative Evaluation of Blood Damage in a Centrifugal VAD by Computational Fluid Dynamics

This study explores a quantitative evaluation of blood damage that occurs in a continuous flow left ventricular assist device (LVAD) due to fluid stress. Computational fluid dynamics (CFD) analysis is used to track the shear stress history of 388 particle streaklines. The accumulation of shear and exposure time is integrated along the streaklines to evaluate the levels of blood trauma. This analysis, which includes viscous and turbulent stresses, provides a statistical estimate of possible damage to cells flowing through the pump. Since experimental data for hemolysis levels in our LVAD are not available, in vitro normalized index of hemolysis values for clinically available ventricular assist devices were compared to our damage indices. This approach allowed for an order of magnitude comparison between our estimations and experimentally measured hemolysis levels, which resulted in a reasonable correlation. This work ultimately demonstrates that CFD is a convenient and effective approach to analyze the Lagrangian behavior of blood in a heart assist device

A Dynamical State Space Representation and Performance Analysis of a Feedback-Controlled Rotary Left Ventricular Assist Device

The left ventricular assist device (LVAD) is a mechanical device that can assist an ailing heart in performing its functions. The latest generation of such devices is comprised of rotary pumps which are generally much smaller, lighter, and quieter than the conventional pulsatile pumps. The rotary pumps are controlled by varying the rotor (impeller) speed. If the patient is in a health care facility, the pump speed can be adjusted manually by a trained clinician to meet the patients blood needs. However, an important challenge facing the increased use of these LVADs is the desire to allow the patient to return home. The development of an appropriate feedback controller for the pump speed is therefore crucial to meet this challenge. In addition to being able to adapt to changes in the patients daily activities by automatically regulating the pump speed, the controller must also be able to prevent the occurrence of excessive pumping (known as suction) which may cause collapse of the ventricle. In this paper we will discuss some theoretical and practical issues associated with the development of such a controller. As a first step, we present and validate a state-space mathematical model, based on a nonlinear equivalent circuit flow model, which represents the interaction of the pump with the left ventricle of the heart. The associated model is a six-dimensional vector of time varying nonlinear differential equations. The time variation occurs over four consecutive intervals representing the contraction, ejection, relaxation, and filling phases of the left ventricle. The pump in the model is represented by a nonlinear differential equation which relates the pump rotational speed and the pump flow to the pressure difference across the pump. Using this model, we discuss a feedback controller which adjusts the pump speed based on the slope of the minimum pump flow signal, which is one of the model state variables that can be measured. The objective of the controller is to increase the speed until the envelope of the minimum pump flow signal reaches an extreme point and maintain it afterwards. Simulation results using the model equipped with this feedback controller are presented for two different scenarios of patient activities. Performance of the controller when measurement noise is added to the pump flow signal is also investigated.