Kurt A. Dasse

Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device

The Thermo Cardiosystems Inc (Woburn, MA) HeartMate 1000 IP left ventricular assist device (LVAD) has been evaluated as a bridge to transplantation in 34 patients for up to 324 days at seven clinical centers in the United States. Sixty-five percent of the patients underwent transplantation, 80% of whom were discharged from the hospital. Six additional control patients, transplant candidates who met the entrance criteria but who did not receive the device, were also included in the study. Although 3 (50%) of the control patients received transplants, all 6 died within 77 days of having met the LVAD inclusion criteria (100% mortality). Complications resulting from use of the device were comparable with those previously reported for all ventricular assist devices, except for thromboembolic events: bleeding, 39%; infection, 25%; and right heart failure, 21%. No device-related thromboembolic events occurred, although 1 patient experienced an event related to a mechanical aortic valve in the native heart. None of the complications had a significant negative association with outcome of the patient except for right heart failure. All survivors had a significant improvement in hepatic function before transplantation. Total bilirubin values were reduced by 60% during LVAD support. No significant differences were observed when total bilirubin values were compared at 30 and 60 days after LVAD support and at 30 and 60 days after transplantation in a cohort of 15 patients (p greater than 0.05). The improvement in renal function was less predictable than that of hepatic function. Creatinine values decreased significantly before transplantation; however, the values measured at 30 and 60 days after transplantation were higher than those measured at the same intervals after LVAD support had been initiated, and this increase is presumably related to the immunosuppressive drugs. In conclusion, the HeartMate 1000 IP LVAD has been shown to be effective in supporting end-stage cardiomyopathy patients to transplantation. Thromboembolism, previously regarded as a serious complication with such devices, has not been a problem with this device. Additional patients are being enrolled into the study to further document the safety and effectiveness of this technology.

Improved mortality and rehabilitation of transplant candidates treated with a long-term implantable left ventricular assist system

ObjectiveThis nonrandomized study using concurrent controls was performed to determine whether the HeartMate implantable pneumatic (IP) left ventricular assist system (LVAS) could provide sufficient hemodynamic support to allow rehabilitation of severely debilitated transplant candidates and to evaluate whether such support reduced mortality before and after transplantation. MethodsOutcomes of 75 LVAS patients were compared with outcomes of 33 control patients (not treated with an LVAS) at 17 centers in the United States. All patients were transplant candidates who met the following hemodynamic criteria: pulmonary capillary wedge pressure ≥ 20 mm Hg with a systolic blood pressure ≤ 80 mm Hg or a cardiac index ≤ 2.0 L/minute/m2. In addition, none of the patients met predetermined exclusion criteria. ResultsMore LVAS patients than control patients survived to transplantation: 53 (71%) versus 12 (36%) (p = 0.001); and more LVAS patients were alive at 1 year: 48 (91%) versus 8 (67%) (p = 0.0001). The time to transplantation was longer in the group supported with the LVAS (average, 76 days; range, <1–344 days) than in the control group (average, 12 days; range, 1–72 days). In the LVAS group, the average pump index (2.77 L/minute/m2) throughout support was 50% greater than the corresponding cardiac index (1.86 L/minute/m2) at implantation (p = 0.0001). In addition, 58% of LVAS patients with renal dysfunction survived, compared with 16% of the control patients (p < 0.001). ConclusionsThe LVAS provided adequate hemodynamic support and was effective in rehabilitating patients based on improved renal, hepatic, and physical capacity assessments over time. In the LVAS

Use of a Left Ventricular Assist Device in an Outpatient Setting

The vented electric Heartmate LVAD (VE-LVAD) (Thermo Cardiosystems, Inc., Woburn, MA) is a reliable, fully portable system that allows selected patients with end-stage cardiomyopathy to undergo outpatient treatment while waiting for heart transplantation. This implantable, pusher-plate LVAD is actuated by an electric motor located within the pump housing. The patient wears external batteries and a system controller, which power and control the LVAD motor through a percutaneous lead. Since May 1991, four men have been supported with the VE-LVAD. They ranged in age from 33 to 50 years (mean, 44.3 years); two had idiopathic cardiomyopathy, and two had ischemic cardiomyopathy. Of the four patients, three underwent support of 196, 219, and 504 days; support in the fourth patient is ongoing at more than 90 days. All four patients were fully rehabilitated to New York Heart Association Class I status. Because they were well and fully mobile, the protocol was amended to allow these patients to leave the hospital in a four phase program that begins with 16 hr day passes and leads to hospital discharge. When patients leave the hospital, they are accompanied by trained family members or friends. The patients who have participated in the program have performed routine activities, attended social events, and spent the night at home. The VE-LVAD system seems safe and appropriate for the outpatient setting in selected patients. Patients have been able to manage the system without assistance from medical or engineering personnel. This initial positive experience with outpatient LVAD treatment demonstrates the potential for providing long-term cardiac support with this type of implantable technology.

Computational characterization of flow and hemolytic performance of the UltraMag blood pump for circulatory support

The Levitronix UltraMag blood pump is a next generation, magnetically suspended centrifugal pump and is designed to provide circulatory support for pediatric and adult patients. The aim of this study is to investigate the hemodynamic and hemolytic characteristics of this pump using the computational fluid dynamics (CFD) approach. The computational domain for CFD analysis was constructed from the three-dimensional geometry (3D) of the UltraMag blood pump and meshed into 3D tetrahedral/hybrid elements. The governing equations of fluid flow were computationally solved to obtain a blood flow through the blood pump. Further, hemolytic blood damage was calculated by solving a scalar transport equation where the scalar variable and the source term were obtained utilizing an empirical power-law correlation between the fluid dynamic variables and hemolysis. To obtain mesh independent flow solution, a comparative examination of vector fields, hydrodynamic performance, and hemolysis predictions were carried out. Different sizes of tetrahedral and tetrahedral/hexahedral mixed hybrid models were considered. The mesh independent solutions were obtained by a hybrid model. Laminar and SST κ-ω turbulence flow models were used for different operating conditions. In order to pinpoint the most significant hemolytic region, the flow field analysis was coupled to the hemolysis predictions. In summary, computational characterization of the device was satisfactorily carried out within the targeted operating conditions of the device, and it was observed that the UltraMag blood pump can be safely operated for its intended use to create a circulatory support for both pediatric and adult-sized patients.

Assessment of hydraulic performance and biocompatibility of a MagLev centrifugal pump system designed for pediatric cardiac or cardiopulmonary support.

The treatment of children with life-threatening cardiac and cardiopulmonary failure is a large and underappreciated public health concern. We have previously shown that the CentriMag is a magnetically levitated centrifugal pump system, having the utility for treating adults and large children (1,500 utilized worldwide). We present here the PediVAS, a pump system whose design was modified from the CentriMag to meet the physiological requirements of young pediatric and neonatal patients. The PediVAS is comprised of a single-use centrifugal blood pump, reusable motor, and console, and is suitable for right ventricular assist device (RVAD), left ventricular assist device (LVAD), biventricular assist device (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed to operate without bearings, seals and valves, and without regions of blood stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag hardware, although the priming volume was reduced from 31 to 14 ml, and the port size reduced from 3/8 to ¼ in. For the expected range of pediatric flow (0.3–3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days, demonstrating acceptable hydraulic function and hemocompatibility. The current results substantiate the performance and biocompatibility of the PediVAS cardiac assist system and are likely to support initiation of a US clinical trial in the future.

Clinical responses to ventricular assistance versus transplantation in a series of bridge to transplant patients.

Hemodynamic and peripheral organ responses to ventricular assistance were compared with transplantation in a cohort of patients bridged with the HeartMate 1000 IP left ventricular assist device (LVAD) (Thermo Cardiosystems Inc., Woburn, MA). The study population included 27 patients that were supported an average of 102 days (range, 15-324 days). Two hepatic (total bilirubin and serum glutamic oxaloacetic transaminase [SGOT]) and two renal (creatinine and blood urea nitrogen [BUN]) parameters were measured: 1) before LVAD insertion, 2) 30 and 60 days during ventricular assistance, 3) before transplantation while still on the VAD, and 4) 30 and 60 days after transplantation. Total bilirubin values were significantly greater just before LVAD implant (2.3 mg/dl) than before transplantation (0.7 mg/dl). Although there was no difference after 30 days of either treatment, the total bilirubin values were greater at 60 days after transplantation (1.1 mg/dl) than at an equivalent time on the LVAD (0.6 mg/dl). The SGOT values were also significantly reduced before transplantation. No differences at 30 and 60 days after either procedure were noticed. Creatinine and BUN values were greater before LVAD implant (1.7 and 37 mg/dl) than before transplantation (1.2 and 19 mg/dl). The creatinine values were also greater after transplantation at 30 and 60 days (2.0 and 1.6 mg/dl) than at comparable intervals after LVAD implantation (1.0 and 1.2 mg/dl), presumably as a result of the use of immunosuppressive drugs. End organ function was markedly improved while on the device, enhancing the physiologic status of the patients before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimization of a miniature Maglev ventricular assist device for pediatric circulatory support.

A miniature Maglev blood pump based on magnetically levitated bearingless technology is being developed and optimized for pediatric patients. We performed impeller optimization by characterizing the hemodynamic and hemocompatibility performances using a combined computational and experimental approach. Both three-dimensional flow features and hemolytic characteristics were analyzed using computational fluid dynamics (CFD) modeling. Hydraulic pump performances and hemolysis levels of three different impeller designs were quantified and compared numerically. Two pump prototypes were constructed from the two impeller designs and experimentally tested. Comparison of CFD predictions with experimental results showed good agreement. The optimized impeller remarkably increased overall pump hydraulic output by more than 50% over the initial design. The CFD simulation demonstrated a clean and streamlined flow field in the main flow path. The numerical results by hemolysis model indicated no significant high shear stress regions. Through the use of CFD analysis and bench-top testing, the small pediatric pump was optimized to achieve a low level of blood damage and improved hydraulic performance and efficiency. The Maglev pediatric blood pump is innovative due to its small size, very low priming volume, excellent hemodynamic and hematologic performance, and elimination of seal-related and bearing-related failures due to adoption of magnetically levitated bearingless motor technology, making it ideal for pediatric applications.

Are there extensions of thick filaments to the Z line in vertebrate and invertebrate striated muscle

The experiments conducted were designed to determine the presence or absence of extensions of the thick, myosin-containing filaments to the Z lines in vertebrate and invertebrate muscle. Traditionally these possible extensions have been referred to as “connecting” filaments; more recently (in vertebrate muscle) as “gap” filaments. We performed serial cross sections of stretched frog sartorius and chameleon tongue muscles, and of flight muscles of the Belostomatid water bug. From these serial sections, we achieved entire myofibrillar filament counts at the level of the A band, and at the I-Z junctional area. Based on our results we conclude that thick filament extensions do not exist in vertebrate muscle, but that they are present in invertebrate flight muscle.

Effects of the pulsatile flow settings on pulsatile waveforms and hemodynamic energy in a PediVAS centrifugal pump.

The objective of this study was to test different pulsatile flow settings of the PediVAS centrifugal pump to seek an optimum setting for pulsatile flow to achieve better pulsatile energy and minimal backflow. The PediVAS centrifugal pump and the conventional pediatric clinical circuit, including a pediatric membrane oxygenator, arterial filter, arterial cannula, and ¼ in circuit tubing were used. The circuit was primed with 40% glycerin water mixture. Postcannula pressure was maintained at 40 mm Hg by a Hoffman clamp. The experiment was conducted at 800 ml/min of pump flow with a modified pulsatile flow setting at room temperature. Pump flow and pressure readings at preoxygenator and precannula sites were simultaneously recorded by a data acquisition system. The results showed that backflows appeared at flow rates of 200–800 ml/min (200 ml/min increments) with the default pulsatile flow setting and only at 200 ml/min with the modified pulsatile flow setting. With an increased rotational speed difference ratio and a decreased pulsatile width, the pulsatility increased in terms of surplus hemodynamic energy and total hemodynamic energy at preoxygenator and precannula sites. Backflows seemed at preoxygenator and precannula sites at a 70% of rotational speed difference ratio. The modified pulsatile flow setting was better than the default pulsatile flow setting in respect to pulsatile energy and backflow. The pulsatile width and the rotational speed difference ratio significantly affected pulsatility. The parameter of the rotational speed difference ratio can automatically increase pulsatility with increased rotational speeds. Further studies will be conducted to optimize the pulsatile flow setting of the centrifugal pump.

Functional and Biocompatibility Performances of an Integrated Maglev Pump-Oxygenator

To provide respiratory support for patients with lung failure, a novel compact integrated pump-oxygenator is being developed. The functional and biocompatibility performances of this device are presented. The pump-oxygenator is designed by combining a magnetically levitated pump/rotor with a uniquely configured hollow fiber membrane bundle to create an assembly free, ultracompact, all-in-one system. The hemodynamics, gas transfer and biocompatibility performances of this novel device were investigated both in vitro in a circulatory flow loop and in vivo in an ovine animal model. The in vitro results showed that the device was able to pump blood flow from 2 to 8 L/min against a wide range of pressures and to deliver an oxygen transfer rate more than 300 mL/min at a blood flow of 6 L/min. Blood damage tests demonstrated low hemolysis (normalized index of hemolysis [NIH] approximately 0.04) at a flow rate of 5 L/min against a 100-mm Hg afterload. The data from five animal experiments (4 h to 7 days) demonstrated that the device could bring the venous blood to near fully oxygen-saturated condition (98.6% +/- 1.3%). The highest oxygen transfer rate reached 386 mL/min. The gas transfer performance was stable over the study duration for three 7-day animals. There was no indication of blood damage. The plasma free hemoglobin and platelet count were within the normal ranges. No gross thrombus is found on the explanted pump components and fiber surfaces. Both in vitro and in vivo results demonstrated that the newly developed pump-oxygenator can achieve sufficient blood flow and oxygen transfer with excellent biocompatibility.