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Continuous-Flow Rotary Left Ventricular Assist Devices with “3rd Generation” Design
Continuous-Flow Rotary Left Ventricular Assist Devices with “3rd Generation” Design Francis D. Pagani, MD, PhD Left ventricular assist device (LVAD) therapy has become an established treatment option for patients with advanced heart failure. Broader application of this therapy has been limited by the risk profile of the current generation of devices. The development of continuous-flow rotary pump technology with noncontact bearing design offers the promise of improved device durability and safety profile. Clinical evaluation of these innovative pump designs are currently underway. Semin Thorac Cardiovasc Surg 20:255-263 © 2008 Elsevier Inc. All rights reserved. KEYWORDS heart failure, left ventricular assist devices, destination therapy, continuous-flow rotary pumps
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eart transplantation remains the most successful longterm surgical treatment option for patients with advanced heart failure refractory to medical therapy.1 Limitations in heart donor availability have prevented a broader application of heart transplantation for the treatment of advanced heart failure.1 As a consequence of limited donor availability, left ventricular assist device (LVAD) therapy has become an established treatment modality for patients with advanced heart failure utilized as either a temporary bridge to heart transplantation2 or as permanent support as an alternative to heart transplantation (i.e., destination therapy).3,4 To date, a majority of patients has been supported by devices engineered with pulsatile, volume displacement design, which include the HeartMate IP1000, VE, or XVE (Thoratec Corp., Pleasanton, CA), Thoratec pVAD or IVAD (Thoratec Corp.), or Novacor (World Heart Corp., Oakland, CA) (Fig. 1).2,5-8 These “1st generation” devices are engineered with an internal reservoir chamber and inflow and outflow valves that permit cyclic filling and emptying of the device with pump actuation elicited by either pneumatic or electrical drive systems. Previous clinical studies have demonstrated the efficacy of these devices with regards to hemodynamic support, improvement in survival to heart transplantation,2 and improvement in survival compared with optimal medical management for patients with severe advanced heart failure Section of Cardiac Surgery, University of Michigan Health System, Ann Arbor, Michigan. Address reprint requests to Francis D. Pagani, MD, PhD, Section of Cardiac Surgery, University of Michigan Health System, Cardiovascular Center, Room 5161, 1500 East Medical Center Drive, SPC 5864, Ann Arbor, MI 48109-5864. E-mail: [email protected]
1043-0679/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2008.08.002
who are not candidates for heart transplantation.3 Pulsatile, volume displacement devices have significant limitations inherent in their engineering design that preclude their practical use for extended mechanical circulatory support. These limitations include a large pump size and requirement for extensive surgical dissection for implant, the requirement that the recipient has a large body habitus, the presence of a large-diameter percutaneous lead for venting of air, and audible pump operation.2,7 The most critical limitation of the majority of these devices has been the high incidence of device malfunctions resulting in death or need for reoperations for device exchange.9-11 The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial demonstrated a survival advantage for left ventricular assist device therapy over optimal medical management for patients with severe, advanced heart failure. This trial established the substantial risk of mechanical failure and device-related complications inherent in the 1st generation pulsatile devices.3 In those patients surviving up to 2 years on device support, nearly 65% had undergone device replacement.11
Development of Continuous-Flow Rotary Pumps The development of continuous-flow rotary pump technology represents an innovative and novel engineering design concept for left ventricular assist devices (Fig. 1).12,13 These devices have now largely replaced the use of the 1st generation pulsatile, volume displacement pumps.14 Within this new classification of continuous-flow rotary pumps is the 255
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Figure 1 Overview of the classification of left ventricular assist devices by design generation. *The HVAD (HeartWare Corp.) utilizes a combination of hydrodynamic and magnetic levitation of the internal impeller. #The DuraHeart (Terumo Corp.) utilizes a hydrodynamic bearing design for backup levitation in the event of failure of the primary magnetic levitation system.
important distinguishing design element of “contact” or “noncontact” bearing design. The term “2nd generation” rotary pump has largely been used to describe those continuous-flow rotary pumps, typically with an “axial” blood flow path, which have an internal rotor within the blood flow path that is suspended by contact bearings (Fig. 2).12,14 However, exceptions and differences in opinion to this general categorization do exist.12 The designation “3rd generation” rotary pump has generally been used to categorize continuous-flow rotary devices with an impeller or rotor suspended in the blood flow path using a “noncontact” bearing design. In the majority of circumstances, this design utilizes a “centrifugal” blood flow path and incorporates either magnetic and/or hydrodynamic levitation of the internal impeller (Figs. 1 and 3).12,13,15-18 Impeller rotation to elicit blood flow is achieved through magnetic coupling to the pump motor. A 3rd generation rotary pump with an axial blood flow path
Figure 2 Schematic representation of a 2nd generation continuousflow rotary pump with an axial blood flow path and contact bearing design suspending the internal rotor. Spinning of the internal rotor is achieved by magnetic coupling between the rotor magnet and external motor. (Figure courtesy of Dr. David Farrar, Thoratec Corp., Pleasanton, CA.) (Color version of figure is available online at http://www.semthorcardiovascsurg.com.)
Figure 3 Example of a 3rd generation continuous-flow rotary pump with centrifugal design incorporating active magnetic levitation and coupling of the internal impeller with a bearingless drive system. (A) Schematic representation of the HeartMate III (Thoratec Corp.). (a) The main flow path from the inflow section; (b) blood flow path through the impeller and the backflow paths above the shroud and between the rotor and motor; (c) outflow path. (Reprinted with permission from Farrar et al.16) (B) Schematic representation of a self-bearing or bearingless drive system in a 3rd generation continuous-flow rotary pump. In a self-bearing system, both the drive and levitation coils share the same stator core. (Reprinted with permission from Takatani S,12 ©2007 Blackwell Publishing Ltd.)
and magnetic levitation of the internal rotor also exists (Incor, Berlin Heart GmbH, Berlin, Germany).15 Levitation systems utilized in 3rd generation rotary pumps suspend the moving impeller within the blood field without any mechanical contact, thus eliminating frictional wear and reducing heat generation that would normally take place at the contact surface with a contact bearing design. These levitation forces may be achieved through magnetic or hydrodynamic bearing design. Magnetic forces may be passive without the consumption of power (permanent magnet) or active (induction of magnetic field with electricity) in design.12,13,16,17 Hydrodynamic levitation depends on fluid forces generated by the rotating impeller to levitate the internal impeller.12,13 Pump designs can be further distinguished by the utilization of hydrodynamic levitation only (VentrAssist; Ventracor Ltd., Sydney, Australia), hydrodynamic levitation working in synergy with magnetic levitation for suspension
Continuous-flow rotary LVADs (HVAD; HeartWare Corp., Miami, FL), or variations of active and/or passive magnetic levitation (DuraHeart; Terumo Corp., Ann Arbor, MI; HeartMate III; Thoratec Corp.; Levacor; World Heart Corp.).12,13,16,17,18 Active magnetic levitation of the impeller typically utilizes complex position sensing and control systems that increase requirements for a larger pump size.12,13,17 Hydrodynamic suspension does not utilize position sensors resulting in a less complicated electronic design and ability to miniaturize pump size. Active magnetic levitation typically achieves larger and less variable tolerances between the rotating impeller and pump housing. The larger tolerances may be important in increasing blood flow around the impeller reducing areas of stasis and reducing the amount of blood trauma resulting in hemolysis. Hydrodynamic levitation has more variation in tolerances, and contact between the impeller and pump housing (“touchdown”) may occur during low RPM speeds or “pump off” situations that do not generate sufficient hydrodynamic forces to levitate the impeller. The design of any levitation system must be adequate to control the six degrees-of-freedom of movement of the suspended impeller. The 3rd generation of rotary pumps can be further distinguished by the design of the motor system that is magnetically-coupled to the internal impeller. These designs may include (1) an external motor-drive system17; (2) direct-drive system15; or (3) self-bearing or bearingless system.13,16,18 In the external motor-drive system, a motor is used to induce a magnetic coupling force to rotate the impeller while a separate levitation system controls the impeller suspension.17 The major limitation of this design is the requirement of mechanical bearings that support the rotation of the external motor. The DuraHeart (Terumo Corp.) is an example of an external motor-driven system (Fig. 4).13,17 In a direct-drive system, the impeller is the motor rotor, while a separate levitation system is built into the system to achieve magnetic levitation. The Incor pump (Berlin Heart GmbH) is an example of a direct-drive motor system.13,15 The Incor pump has the feature of being a 3rd generation rotary pump with axial design and magnetic levitation of the internal rotor (Fig. 5). In a self-bearing or bearingless system, both the drive and the levitation coils share the same stator core (Fig. 3).12,13,16,18 Impeller rotation is caused by a moving magnetic field generated by the drive coils.12,13,16,18 No separate motor or bearings are utilized in this design. Examples of this design include the Levacor (World Heart Corp.)18 and HeartMate III (Thoratec Corp.)16,19 (Fig. 3). Again, there are general variations to this classification particularly with regards to the mechanism of impeller levitation. The application of magnetic levitation of the impeller for rotary blood pumps was reported by Akamatsu and colleagues in 199220,21 and by Allaire and colleagues in 1996.22
Rational for Development of 3rd Generation Rotary Pumps Device designs incorporating 2nd generation rotary pump technology with axial configuration have accumulated signif-
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Figure 4 DuraHeart left ventricular assist device: continuous-flow rotary pump with centrifugal design incorporating an external motor-drive system with magnetic levitation of the impeller. (A) Components of the DuraHeart system: upper housing containing the electromagnets and position sensors for primary levitation control of the impeller. Impeller with coupling magnets that permit the external motor-drive system (brushless DC motor) to rotate the impeller. Bottom housing containing the external motor-drive system. (Photograph courtesy of Dr. C. Nojiri, Terumo Corp., Ann Arbor, MI.) (B) Schematic of the DuraHeart left ventricular assist device. (Reprinted with permission from Hoshi et al.13) (Color version of figure is available online at http://www.semthorcardiovascsurg. com.)
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Figure 5 (A) Incor (Berlin Heart GmbH) left ventricular assist device incorporating axial design with magnetic levitation of the rotor. (B) Levitation and drive system schematic. (Reprinted with permission from Hoshi et al.13)
icant human clinical experience and are either currently in late stages of clinical trials in the United States or have recently been approved by the Food and Drug Administration (FDA) for bridge to transplant indication (Fig. 1).14,23,24 The 2nd generation rotary pumps have the advantage of a smaller pump size and potential for greater long-term mechanical reliability by elimination of the reservoir chamber and inflow and outflow valves needed for the 1st generation of pulsatile pump designs.14,23,24 Reports from clinical trials of the 2nd generation rotary pumps have demonstrated efficacy in providing hemodynamic support, a favorable risk to benefit assessment, and improvement in mechanical performance.14,24 Further, the human experience with 2nd generation rotary pumps with axial design has established the long-term safety of mechanical circulatory support with minimal pulse pressure.25,26 Results from clinical studies have demonstrated early improvement followed by long-term stability of renal and hepatic function and no adverse effects on neurocognitive performance.14,25,26 These improvements in device technology with the 2nd generation of continuous-flow rotary pumps with axial design have increased the acceptance of LVAD therapy for long-term mechanical circulatory support, although world-wide use of LVAD therapy for destination therapy still remains limited.
F.D. Pagani Although significant improvements in pump design have occurred with the 2nd generation of rotary pump with an axial blood flow path compared with the 1st generation of pulsatile devices, there remain a number of potential concerns with this technology. The presence of contact bearings to suspend the rotor represents a potential point of frictional wear resulting in device failure and subsequent need for device exchange.12,13 The 2nd generation rotary pumps with axial design still demonstrate the potential for thrombus formation on the device rotor and bearing interface due to the presence of stasis and incomplete bearing “wash.”14,23,27 However, the concern for development of thrombus on the rotor and bearing contact points has varied significantly with different 2nd generation rotary pumps.27 The presence of stators to suspend and redirect blood flow also represents an obstruction within the blood flow path. Thrombosis from blood stasis can be caused by blood flow disturbances and recirculating zones associated with the supports required by contact bearing design. Clinical studies have documented the problem with device thrombus requiring device exchange or treatment with thrombolytic therapy, and have also shown a reduced but persistent risk of stroke.14,27 A significant proportion of strokes reported during clinical trials with 2nd generation devices have occurred early following surgery and were associated with the implant procedure, likely representing air or particulate emboli possibly from sources other than the device. The proportion of strokes that are attributable to transient thrombus formation within the pump or thrombus formation within the heart is unknown. In addition, this technology still requires long-term antithrombotic therapy and, subsequently, hemorrhagic complications are observed with this therapy.14,23,24 An additional potential concern of 2nd generation rotary pumps with axial design is related to its hydrodynamic performance. To observe changes in pump flow at a fixed rotor speed, significant changes in pressure across the inlet and outlet orifices of the pump must occur.28,29 This relative degree of insensitivity of the hydrodynamic performance of the pump or “steep” pressure-flow relationship can result in left ventricular collapse and “suction” when filling pressures are abruptly reduced as in the case of a sudden onset of a ventricular arrhythmia, or result in elevated filling pressures with dyspnea when return to the left atrium is abruptly increased, as with exercise. Left ventricular collapse or “suction” event can, by itself, precipitate serious ventricular arrhythmias,30 and the inability to significantly increase pump flow with exercise may limit exercise performance in patients with axial pumps. However, the latter concern has not been observed in clinical exercise studies in humans.31 Algorithms for demand-responsive control for rotary pumps have been developed to overcome this perceived limitation in pump design.32
Design Features of 3rd Generation Continuous-Flow Rotary Pumps The persistent concern with limitations of the device technology of the 2nd generation of rotary pumps have led to further
Continuous-flow rotary LVADs improvements in device design leading to a 3rd generation of devices with continuous-flow rotary technology with centrifugal configuration and noncontact bearing design.12,13,15-18 The major advancement in design of the 3rd generation of rotary pumps has been the feature of magnetic and/or hydrodynamic levitation of the impeller with elimination of contact bearings within the pump.12,13,15-18 The elimination of contact bearings has the potential to significantly improve durability. The elimination of contact bearings along with magnetic levitation of the impeller results in a greater degree of blood flow around the suspended impeller and “washing” of the impeller that is perceived to be a major benefit in terms of reducing the risk of thrombus formation within the pump and perhaps reducing the intensity of antithrombotic therapy necessary with this technology.33 The 3rd generation of rotary pumps with centrifugal design have a more sensitive pressure-flow relationship compared with the 2nd generation of rotary pumps with axial design (Fig. 6).16,34 This greater sensitivity of the pressure-flow relationship in 3rd generation rotary pumps with centrifugal design results in greater changes in flow for any given change in pressure across the inlet and outlet orifices of the pump (Fig. 6). This greater pump response to changes in flow increases the margin of safety from creating suction events and improves pump flow during increases in left atrial return potentially enhancing exercise response. Further, the “flat” or sensitive pressure-flow characteristics of the 3rd generation of rotary pumps with centrifugal design increases the reliability of the estimated flow from pump power and rotor speed.35,36 In terms of its physical size, a 3rd generation rotary pump with full active magnetic-levitation of the impeller will never be as small as a 2nd generation rotary pump with axial design and mechanical bearing support of the rotor. However, the improvements in other design attributes of the 3rd generation of rotary pumps with centrifugal design, such as mechanical wear, operation at low flow, and perceived improved potential for hemocompatibility, while still maintaining a manageable size, warrant further clinical investigation.13 Whether these attributes of the 3rd generation of rotary pumps with centrifugal design will result in significant improvement in clinical outcomes over that observed with the 2nd generation of rotary pumps with axial design is not known at this time.
3rd Generation Rotary Pumps Currently in Clinical Evaluation VentrAssist The VentrAssist device (Ventracor Ltd.) is a continuous-flow rotary pump with centrifugal and noncontact bearing design. The device weighs 298 g, and measures 60 mm in diameter (Fig. 7).37,38 The operating range of the pump is 1,800 to 3,000 revolutions per minute (rpm) in the normal setting. The impeller is comprised of four small blades that are embedded with permanent magnets. The impeller blades act as a rotor for the pump’s brushless DC motor and spin when an electrical current is sequentially switched between three pairs of coils contained within the titanium housing of the pump.
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Figure 6 (A) Typical pressure-flow relations of the HeartMate III, 3rd generation centrifugal pump are compared with the HeartMate II, 2nd generation axial flow pump at two different speed ranges. The pressure-flow curves are similar at high flows, but the HeartMate III has a “flatter” relationship at lower flows. (Reprinted with permission from Farrar et al.16) (B) Demonstration of the greater sensitivity of the pressure-flow relationship of centrifugal-compared with axial-flow pumps. (Diagram courtesy of Dr. C. Nojiri, Terumo Corp., Ann Arbor, MI.)
Suspension of the impeller within the pump cavity is performed passively and is achieved entirely through the use of eight hydrodynamic bearings, one on each face of the four blades. No magnetic levitation is utilized in the levitation of the impeller. Dynamic interplay between the eight hydrodynamic bearing forces, fluid forces and gravitational forces prevents the spinning impeller from touching any part of the housing of the pump. The absence of magnetic levitation and monitoring systems to identify impeller position results in a less complicated electronics and smaller pump design. Clinical trials of the VentrAssist have been completed in Australia and Europe and are currently being conducted in the United States as part of a FDA-approved pivotal trial for both bridge to transplant and destination therapy indications.37,38 Initial clinical reports of the VentrAssist performance have demonstrated a satisfactory efficacy and risk profile of the device. Overall survival for 30 patients undergoing
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0.01 events per patient-month of support after 30 days. Device malfunctions included outflow graft leak (two), initial pump nonrestart following elective stop (one), inappropriate alarms (two), and accidental percutaneous lead transaction (one). As of January 30, 2007, a total of 87 patients have been implanted with the VentrAssist at 14 centers worldwide, yielding a total exposure time of more than 43 patient-years and a maximum implant duration of 2.7 years.
DuraHeart The DuraHeart (Terumo Corp.) is a continuous-flow rotary pump with centrifugal and noncontact bearing design (Figs. 4 and 8).13,17,34 The device has a displacement volume of 180 cm3 and a weight of 540 g. Its external dimensions are 72 mm in width and 45 mm in height. The pumping unit consists of an upper housing with the levitation system, impeller, and bottom housing containing the external-drive motor. The device is designed with active magnetic levitation of the impeller along with hydrodynamic bearings to support impeller levitation in case of failure of the magnetic levitation system. The impeller is rotated through magnetic coupling between permanent magnets embedded on the motor side of the impeller and an external-drive motor that utilizes a bearing design. Three electromagnets and three position sensors are mounted in the upper housing. Tilting and axial displacements of the impeller are monitored and controlled using a three degrees-of-freedom control. The ferromagnetic ring on the opposite side of the impeller is levitated by the electromagnet, and position sensors control the impeller so that it is always positioned at the center of the blood chamber. Radial impeller movement is passively suspended with a bias flux through electromagnetic rotor and drive magnet rotor.
Figure 7 (A) VentrAssist (Ventracor Ltd.) left ventricular assist device. (B) Internal view demonstrating the impeller that is comprised of four small blades that are embedded with permanent magnets. The impeller blades act as a rotor for the pump’s brushless DC motor and spin when an electrical current is sequentially switched between three pairs of coils contained within the titanium housing of the pump. (Photographs courtesy of Ventracor Ltd., Sydney, Australia). (Color version of figure is available online at http:// www.semthorcardiovascsurg.com.)
device implantation as a bridge to transplant was 86% at 22 weeks. At 22 weeks, 40% of patients had undergone heart transplantation, 13% of patients died while on device support, 3% of patients underwent device explantation for cardiac recovery, and 43% remained alive with ongoing device support. The most common protocol-defined, device-related serious adverse event was infection with 16 events occurring in 11 patients. The majority of infections occurred after 30 days. The rate of device-related infection within the first 30 days was 0.11 events per patient-month of support and 0.17 events per patient-month of support after 30 days. The occurrence of stroke was greatest in the first 30 days with an event rate of 0.18 events per patient-month of support and
Figure 8 DuraHeart Left Ventricular Assist Device. (Photograph courtesy of Dr. C. Nojiri, Terumo Corp., Ann Arbor, MI.)
Continuous-flow rotary LVADs Clinical evaluation of the DuraHeart device has recently concluded in Europe and clinical evaluation of the device in the United States is scheduled for 2008. A preliminary report of the European experience was recently presented at the International Society of Heart and Lung Transplantation in April of 2008.39 Thirty-five patients with advanced heart failure (NYHA class IV, 14 ischemic, 5 females), who were eligible for heart transplantation underwent implantation of the DuraHeart device from January of 2004 through September of 2007. Median age of the patients was 56 (range 29-73) years with a median body surface are of 1.9 (1.4-2.4) m2. The average duration of device support was 330 ⫾ 220 (17-808) days with a cumulative duration of 21 years. Fourteen patients (40%) underwent heart transplantation at 194 ⫾ 146 days. Nineteen patients (54%) were supported for at least 6 months and seven (20%) patients were supported for greater than 1 year. Fourteen patients (40%) remain alive with ongoing device support (330 ⫾ 292) days. Kaplan-Meier survival at 2 years was 78%. There were seven deaths (median time to deaths: 29 days). Six early deaths occurred for the initial 11 patients and four were associated with excessive anticoagulation/antiplatelet therapy that resulted in fatal intracerebral hemorrhage or subdural hematoma. After implementing less intensive anticoagulation and antiplatelet therapy comparable to mechanical heart valves, there was no ischemic or hemorrhagic stroke for the last 24 patients. Stroke-free survival for the last 24 patients was 94% at 2 years. Twenty-six patients (86% of 1 month survivors) were discharged home, and the readmission rate was 1.5/pt-y. There were no pump mechanical failures, pump thrombosis, or hemolysis throughout the support duration.
HVAD The HVAD (HeartWare Corp.) is a small continuous-flow rotary pump with centrifugal and noncontact bearing design (Fig. 9). The unique feature of the HVAD is its small design size.40,41 It has a displacement volume of 45 mL, and weighs 145 g with a flow capacity of up to 10 L/min. The device is small enough to place within the pericardial cavity without the need for dissection and creation of a preperitoneal pocket. The HVAD uses a wide-blade impeller design to maximize performance and hemocompatibility, size minimization, long-term reliability, and overall system efficiency. The impeller is suspended in place by combination of passive magnetic and hydrodynamic bearing systems to avoid mechanical contact and wear. The design integrates two motor stators for single-motor fault protection to increase reliability. The impeller suspension system uses a passive magnetic bearing for radial stiffness. Axial magnetic preload and hydrodynamic bearings on top of each impeller blade provide axial constraint. The magnetic bearing consists of a stack of rare earth ring magnets near the impeller’s inside diameter that repel the magnetic force of a similar stack of magnets inside the center post. The axial alignment of the center-post magnet stack is set to provide an axial force that pushes the impeller toward the forward housing (the assembly with the inflow cannula). Physical contact between the housing and
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Figure 9 HVAD (HeartWare Corp.). (Photograph courtesy of HeartWare Corp., Miami, FL.) (Color version of figure is available online at http://www.semthorcardiovascsurg.com.)
the impeller is prevented by a thin blood film generated by the hydrodynamic bearings. The hydrodynamic bearings feature a shrouded design that is intended to maximize the blood-film thickness and improve surface washing. The HVAD has undergone clinical evaluation in Europe and Australia and is scheduled to begin clinical evaluation in the United States in 2008. In a multi-institutional trial in Europe and Australia, 20 patients underwent implantation of the HVAD from March of 2006 through September of 2007.40 Mean age of the patients was 46 ⫾ 12 years (range 28-68 years). Median cardiopulmonary bypass time to implant the device was 67 min (range 21-140 min). Mean duration of HVAD device support was 167 ⫾ 143 days (range 13-425 days). Range of blood flow provided by the pump was 4.0-6.5 L/min. Three patients were successfully transplanted after 426, 349, and 157 days, respectively. One patient was weaned from pump support on postoperative day 266, two patients died on device (postoperative days 13 and 203), and 14 patients remain alive with ongoing device support. Actuarial survival at 1 year was 80%.
Levacor The Levacor device (World Heart Corp.) is a continuous-flow rotary pump with centrifugal and noncontact bearing design (Fig. 10).13,18,42 The pump is 35-mm high and 75 mm in diameter. Its weight is 440 g with 22-mL priming volume. The magnetic levitation system utilizes a combination of permanent magnets that provide passive levitation, and a magnet coil that provides active levitation along one degree-offreedom of movement of the impeller. To minimize power consumption, the passive and active levitation elements function together, permitting the passive levitation to counteract almost all of the mechanical force on the rotor. This is done using a method of control known as virtual zero power control.13,18,42 Aside from rotation, the other five degrees-of-
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were transplanted, 11 (5%) were explanted (weaned from the system), 43 (20%) remain alive with ongoing pump support, and 93 (44%) of patients died on the system. The major cause of death was multiorgan failure in 47 (22%) patients followed by cerebrovascular events in 17 cases. Other causes of death were right ventricular failure, five cases (2%); trauma, two cases (1%); cancer, three cases (1%); and others or unknown, 20 cases (9%). Fifty-one patients (21%) were discharged home on the device. There were no deaths related to device failure.
Summary
Figure 10 Levacor left ventricular assist device (World Heart Corp.). (Figure courtesy of World Heart Corp., Oakland, CA.)
freedom of movement of the pump rotor are all passively controlled except axial movement in the z-direction, which is actively controlled by the coil and electronics. The motor is integrated directly into the pump housing and rotor and no external motor is required for rotation. Clinical evaluation of the Levacor device has been initiated in Europe and Canada with successful results reported in a bridge to recovery protocol.42 Clinical evaluation in the United States is scheduled for 2008.
Incor The Incor (Berlin Heart GmbH) is an example of a continuous-flow rotary pump with axial design and magnetic levitation of the rotor using a direct-drive mechanism (Fig. 5).13,15,43-45 The pump weighs 200 g, has an axial direction of 120 mm, an outer diameter of 30 mm, and a volume of 80 mL. Axial impeller movement is monitored by a position sensor and controlled actively by the two electromagnets mounted at both ends of the rotor. Radial and tilting impeller movements are passively controlled. The levitated impeller can be rotated at speeds between 5,000 and 10,000 rpm generating up to 5 L/min of flow against a pressure of 100 mm Hg with a magnetic levitation power consumption of 2 to 4 W. The motor efficiency of more than 90% and power consumption ⬍4 W ensure that the pump does not generate any significant amount of heat. The control software enables monitoring of the pressure gradient and the flow by detection of the rotor’s position in the magnetic field. The flow straighter and diffuser are adapted for inflow and outflow passage, respectively, to reduce the spin of blood flow and add to the pressure buildup. All blood-contacting surfaces are heparin coated by the Carmeda process. Clinical evaluation of the Incor device was initiated in Europe in June of 2002 with a total of 212 implants reported worldwide.13,15,41,42,43 The mean patient age was 51.5 ⫾ 13 years (range 16-72 years), and 24 patients (11.3%) were female. The mean duration of support on the device was 162 ⫾ 182 days (maximum: 1071 days). Sixty-five (31%) patients
Third generation, continuous-flow pumps with noncontact bearing design offer the potential of enhanced durability and safety for extended mechanical circulatory support. Early clinical experience with these devices demonstrate efficacy with regard to hemodynamic support. Further clinical evaluation will be necessary to determine if the improved hydrodynamic properties of centrifugal pumps and potential enhanced durability of a noncontact bearing design are associated with improvements in patient outcomes.
References 1. Aurora P, Boucek MM, Christie J, et al: Registry of the International Society for Heart and Lung Transplantation: tenth official pediatric lung and heart/lung transplantation report–2007. J Heart Lung Transplant 26:1223-1228, 2007 2. Frazier OH, Rose EA, Oz MC, et al: Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation. J Thorac Cardiovasc Surg 122:11861195, 2001 3. Rose EA, Gelijns AC, Moskowitz AJ, et al: Long-term use of a left ventricular assist device for end-stage heart failure. N Eng J Med 345: 1435-1443, 2001 4. Park SJ, Tector A, Piccioni W, et al: Left ventricular assist devices as destination therapy: a new look at survival. J Thorac Cardiovasc Surg 129:9-17, 2005 5. Joyce LD, Noon GP, Joyce DL, et al: Mechanical circulatory support–a historical review. ASAIO J 50:x-xii, 2004 6. Slaughter MS, Tsui SS, El-Banayosy A, et al: Results of a multicenter clinical trial with the Thoratec Implantable Ventricular Assist Device. J Thorac Cardiovasc Surg 133:1573-1580, 2007 7. El-Banayosy A, Arusoglu L, Kizner L, et al: Novacor left ventricular assist system versus HeartMate vented electric left ventricular assist system as a long-term mechanical circulatory support device in bridging patients: a prospective study. J Thorac Cardiovasc Surg 119:581587, 2000 8. McBride LR, Naunheim KS, Fiore AC, et al: Clinical experience with 111 Thoratec ventricular assist devices. Ann Thorac Surg 67:12331239, 1999 9. Dowling RD, Park SJ, Pagani FD, et al: HeartMate VE LVAS design enhancements and its impact on device reliability. Eur J Cardiothorac Surg 25:958-963, 2004 10. Pagani FD, Long JW, Dembitsky WP, et al: Improved Mechanical Reliability of the HeartMate XVE Left Ventricular Assist System. Ann Thorac Surg 82:1413-1419, 2006 11. Dembitsky WP, Tector AJ, Park S, et al: Left ventricular assist device performance with long-term circulatory support: lessons from the REMATCH trial. Ann Thorac Surg 78:2123-2130, 2004 12. Takatani S: Progress of rotary blood pumps: Presidential Address. International Society for Rotary Blood Pumps 2006, Leuven, Belgium. Artif Organs 31:329-344, 2007
Continuous-flow rotary LVADs 13. Hoshi H, Shinshi T, Takatani S: Third generation blood pumps with mechanical noncontact magnetic bearings. Artif Organs 30:324-338, 2006 14. Miller LW, Pagani FD, Russell SD, et al: Use of a continuous-flow device in patients awaiting heart transplantation. New Engl J Med 357:885896, 2007 15. Schmid C, Tjan T, Etz C, et al: First clinical experience with the Incor left ventricular assist device. J Heart Lung Transplant 24:1188-1194, 2005 16. Farrar DJ, Bourque K, Dague CP, et al. Design features, developmental status, and experimental results with the HeartMate III centrifugal left ventricular assist system with a magnetically levitated rotor. ASAIO J 53:310-315, 2007 17. Nojiri C, Kijima T, Maekawa J, et al: Development status of Terumo implantable left ventricular assist system. Artif Organs 25:411-413, 2001 18. Bearnson GB, Jacobs GB, Kirk J, et al: HeartQuest ventricular assist device magnetically levitated centrifugal blood pump. Artif Organs 30:339-346, 2006 19. Bourque K, Gernes DB, Loree III HM, et al: HeartMate III: pump design for a centrifugal LVAD with a magnetically levitated rotor. ASAIO J 47:401-405, 2001 20. Akamatsu T, Nakazeki T, Itoh H: Centrifugal blood pump with a magnetically suspended impeller. Artif Organs 16:305-308, 1992 21. Akamatsu T, Tsukiya T, Nishimura K, et al: Recent studies of the centrifugal blood pump with a magnetically suspended impeller. Artif Organs 19:631-634, 1995 22. Allaire PE, Kim HC, Maslen EH, et al: Prototype continuous flow ventricular assist device supported on magnetic bearings. Artif Organs 20:582-590, 1996 23. Goldstein DJ, Zucker M, Arroyo L, et al: Safety and feasibility trial of the MicroMed DeBakey ventricular assist device as a bridge to transplantation. J Am Coll Cardiol 45:962-963, 2005 24. Siegenthaler MP, Frazier OH, Beyersdorf F, et al: Mechanical reliability of the Jarvik 2000 Heart. Ann Thorac Surg 81:1752-1758, 2006 25. Radovancevic B, Vrtovec B, de Kort E, et al: End-organ function in patients on long-term circulatory support with continuous- or pulsatile-flow assist devices. J Heart Lung Transplant 26:815-818, 2007 26. Westaby S, Banning AP, Jarvik R, et al: First permanent implant of the Jarvik 2000 heart. Lancet 356:900-903, 2000 27. Jahanyar J, Noon GP, Koerner MM, et al: Recurrent device thrombi during mechanical circulatory support with an axial-flow pump is a treatable condition and does not preclude successful long-term support. J Heart Lung Transplant 26:200-203, 2007 28. Stepanoff AJ: Centrifugal and Axial Flow Pumps: Theory, Design, and Application (ed 2). New York, John Wiley and Sons, 1957 29. Akimoto T, Yamazaki K, Litwak P, et al: Rotary blood pump flow spontaneously increases during exercise under constant pump speed: results of a chronic study. Artif Organs 23:797-801, 1999
263 30. Vollkron M, Voitl P, Ta J, et al: Suction events during left ventricular support and ventricular arrhythmias. J Heart Lung Transplant 26: 819-825, 2007 31. Haft J, Armstrong W, Dyke DB, et al: Hemodynamic and exercise performance with pulsatile and continuous flow left ventricular assist devices. Circulation 116:I-8-I-15, 2007 (suppl I) 32. Schima H, Vollkron M, Jantsch U, et al: Clinical experience with an automatic control system for rotary blood pumps during ergometry and right-heart catheterization. J Heart Lung Transplant 25:167-173, 2006 33. Saito S, Westaby S, Piggot D, et al: Reliable long-term non-pulsatile circulatory support without anticoagulation. Eur J Cardiothorac Surg 19:678-683, 2001 34. Nishinaka T, Schima H, Roethy W, et al: The DuraHeart VAD, a magnetically levitated centrifugal pump. The University of Vienna bridge to transplant experience. Circ J 70:1421-1425, 2006 35. Ayre PJ, Vidakovic SS, Tansley GD, et al: Sensorless flow and head estimation in the VentrAssist rotary blood pump. Artif Organs 24:585588, 2000 36. Tsukiya T, Akamatsu T, Nishimura K, et al: Use of motor current in flow rate measurement for magnetically suspended centrifugal blood pump. Artif Organs 21:396-401, 1997 37. Esmore D, Spratt P, Larbalestier R, et al: VentrAssist left ventricular assist device: clinical trial results and clinical development plan update. Eur J Cardiothorac Surg 32:735-744, 2007 38. Esmore DS, Kaye D, Salamonsen R, et al: First clinical implant of the VentrAssist left ventricular assist system as destination therapy for endstage heart failure. J Heart Lung Transplant 24:1150-1154, 2005 39. Nojiri C, Fey O, Jaschke F, et al: Long-term circulatory support with the DuraHeart mag-lev centrifugal left ventricular assist system for advanced heart failure patients eligible to transplantation: European experiences. J Heart Lung Transplant 27:S245, 2008 40. Wieselthaler GM, Strueber M, O’Driscoll GA, et al: Experience with the novel HeartWare HVAD with hydromagnetically levitated rotor in a multi-institutional trial. J Heart Lung Transplant 27:S245, 2008 41. Tuzun E, Roberts K, Cohn WE, et al: In vivo evaluation of the HeartWare centrifugal ventricular assist device. Texas Heart Inst J 34:406411, 2007 42. Pitsis AA, Visouli AN, Vassilikos V, et al: First human implantation of a new rotary blood pump: design of the clinical feasibility study. Hellenic J Cardiol 47:368-376, 2006 43. Hetzer R, Weng Y, Potapov EV, et al: First experiences with a novel magnetically suspended axial flow left ventricular assist device. Eur J Cardiothorac Surg 25:964-970, 2004 44. Göttel P, Hetzer R, Schmid C, et al: Clinical results of the first 99 patients with the axial flow pump: Incor. J Heart Lung Transplant 24:S57, 2005 45. Schmid C, Jurmann M, Birnbaum D, et al: Influence of inflow cannula length in axial-flow pumps on neurologic adverse event rate: results from a multicenter analysis. J Heart Lung Transplant 27:253-260, 2008
H
eart transplantation remains the most successful longterm surgical treatment option for patients with advanced heart failure refractory to medical therapy.1 Limitations in heart donor availability have prevented a broader application of heart transplantation for the treatment of advanced heart failure.1 As a consequence of limited donor availability, left ventricular assist device (LVAD) therapy has become an established treatment modality for patients with advanced heart failure utilized as either a temporary bridge to heart transplantation2 or as permanent support as an alternative to heart transplantation (i.e., destination therapy).3,4 To date, a majority of patients has been supported by devices engineered with pulsatile, volume displacement design, which include the HeartMate IP1000, VE, or XVE (Thoratec Corp., Pleasanton, CA), Thoratec pVAD or IVAD (Thoratec Corp.), or Novacor (World Heart Corp., Oakland, CA) (Fig. 1).2,5-8 These “1st generation” devices are engineered with an internal reservoir chamber and inflow and outflow valves that permit cyclic filling and emptying of the device with pump actuation elicited by either pneumatic or electrical drive systems. Previous clinical studies have demonstrated the efficacy of these devices with regards to hemodynamic support, improvement in survival to heart transplantation,2 and improvement in survival compared with optimal medical management for patients with severe advanced heart failure Section of Cardiac Surgery, University of Michigan Health System, Ann Arbor, Michigan. Address reprint requests to Francis D. Pagani, MD, PhD, Section of Cardiac Surgery, University of Michigan Health System, Cardiovascular Center, Room 5161, 1500 East Medical Center Drive, SPC 5864, Ann Arbor, MI 48109-5864. E-mail: [email protected]
1043-0679/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2008.08.002
who are not candidates for heart transplantation.3 Pulsatile, volume displacement devices have significant limitations inherent in their engineering design that preclude their practical use for extended mechanical circulatory support. These limitations include a large pump size and requirement for extensive surgical dissection for implant, the requirement that the recipient has a large body habitus, the presence of a large-diameter percutaneous lead for venting of air, and audible pump operation.2,7 The most critical limitation of the majority of these devices has been the high incidence of device malfunctions resulting in death or need for reoperations for device exchange.9-11 The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial demonstrated a survival advantage for left ventricular assist device therapy over optimal medical management for patients with severe, advanced heart failure. This trial established the substantial risk of mechanical failure and device-related complications inherent in the 1st generation pulsatile devices.3 In those patients surviving up to 2 years on device support, nearly 65% had undergone device replacement.11
Development of Continuous-Flow Rotary Pumps The development of continuous-flow rotary pump technology represents an innovative and novel engineering design concept for left ventricular assist devices (Fig. 1).12,13 These devices have now largely replaced the use of the 1st generation pulsatile, volume displacement pumps.14 Within this new classification of continuous-flow rotary pumps is the 255
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Figure 1 Overview of the classification of left ventricular assist devices by design generation. *The HVAD (HeartWare Corp.) utilizes a combination of hydrodynamic and magnetic levitation of the internal impeller. #The DuraHeart (Terumo Corp.) utilizes a hydrodynamic bearing design for backup levitation in the event of failure of the primary magnetic levitation system.
important distinguishing design element of “contact” or “noncontact” bearing design. The term “2nd generation” rotary pump has largely been used to describe those continuous-flow rotary pumps, typically with an “axial” blood flow path, which have an internal rotor within the blood flow path that is suspended by contact bearings (Fig. 2).12,14 However, exceptions and differences in opinion to this general categorization do exist.12 The designation “3rd generation” rotary pump has generally been used to categorize continuous-flow rotary devices with an impeller or rotor suspended in the blood flow path using a “noncontact” bearing design. In the majority of circumstances, this design utilizes a “centrifugal” blood flow path and incorporates either magnetic and/or hydrodynamic levitation of the internal impeller (Figs. 1 and 3).12,13,15-18 Impeller rotation to elicit blood flow is achieved through magnetic coupling to the pump motor. A 3rd generation rotary pump with an axial blood flow path
Figure 2 Schematic representation of a 2nd generation continuousflow rotary pump with an axial blood flow path and contact bearing design suspending the internal rotor. Spinning of the internal rotor is achieved by magnetic coupling between the rotor magnet and external motor. (Figure courtesy of Dr. David Farrar, Thoratec Corp., Pleasanton, CA.) (Color version of figure is available online at http://www.semthorcardiovascsurg.com.)
Figure 3 Example of a 3rd generation continuous-flow rotary pump with centrifugal design incorporating active magnetic levitation and coupling of the internal impeller with a bearingless drive system. (A) Schematic representation of the HeartMate III (Thoratec Corp.). (a) The main flow path from the inflow section; (b) blood flow path through the impeller and the backflow paths above the shroud and between the rotor and motor; (c) outflow path. (Reprinted with permission from Farrar et al.16) (B) Schematic representation of a self-bearing or bearingless drive system in a 3rd generation continuous-flow rotary pump. In a self-bearing system, both the drive and levitation coils share the same stator core. (Reprinted with permission from Takatani S,12 ©2007 Blackwell Publishing Ltd.)
and magnetic levitation of the internal rotor also exists (Incor, Berlin Heart GmbH, Berlin, Germany).15 Levitation systems utilized in 3rd generation rotary pumps suspend the moving impeller within the blood field without any mechanical contact, thus eliminating frictional wear and reducing heat generation that would normally take place at the contact surface with a contact bearing design. These levitation forces may be achieved through magnetic or hydrodynamic bearing design. Magnetic forces may be passive without the consumption of power (permanent magnet) or active (induction of magnetic field with electricity) in design.12,13,16,17 Hydrodynamic levitation depends on fluid forces generated by the rotating impeller to levitate the internal impeller.12,13 Pump designs can be further distinguished by the utilization of hydrodynamic levitation only (VentrAssist; Ventracor Ltd., Sydney, Australia), hydrodynamic levitation working in synergy with magnetic levitation for suspension
Continuous-flow rotary LVADs (HVAD; HeartWare Corp., Miami, FL), or variations of active and/or passive magnetic levitation (DuraHeart; Terumo Corp., Ann Arbor, MI; HeartMate III; Thoratec Corp.; Levacor; World Heart Corp.).12,13,16,17,18 Active magnetic levitation of the impeller typically utilizes complex position sensing and control systems that increase requirements for a larger pump size.12,13,17 Hydrodynamic suspension does not utilize position sensors resulting in a less complicated electronic design and ability to miniaturize pump size. Active magnetic levitation typically achieves larger and less variable tolerances between the rotating impeller and pump housing. The larger tolerances may be important in increasing blood flow around the impeller reducing areas of stasis and reducing the amount of blood trauma resulting in hemolysis. Hydrodynamic levitation has more variation in tolerances, and contact between the impeller and pump housing (“touchdown”) may occur during low RPM speeds or “pump off” situations that do not generate sufficient hydrodynamic forces to levitate the impeller. The design of any levitation system must be adequate to control the six degrees-of-freedom of movement of the suspended impeller. The 3rd generation of rotary pumps can be further distinguished by the design of the motor system that is magnetically-coupled to the internal impeller. These designs may include (1) an external motor-drive system17; (2) direct-drive system15; or (3) self-bearing or bearingless system.13,16,18 In the external motor-drive system, a motor is used to induce a magnetic coupling force to rotate the impeller while a separate levitation system controls the impeller suspension.17 The major limitation of this design is the requirement of mechanical bearings that support the rotation of the external motor. The DuraHeart (Terumo Corp.) is an example of an external motor-driven system (Fig. 4).13,17 In a direct-drive system, the impeller is the motor rotor, while a separate levitation system is built into the system to achieve magnetic levitation. The Incor pump (Berlin Heart GmbH) is an example of a direct-drive motor system.13,15 The Incor pump has the feature of being a 3rd generation rotary pump with axial design and magnetic levitation of the internal rotor (Fig. 5). In a self-bearing or bearingless system, both the drive and the levitation coils share the same stator core (Fig. 3).12,13,16,18 Impeller rotation is caused by a moving magnetic field generated by the drive coils.12,13,16,18 No separate motor or bearings are utilized in this design. Examples of this design include the Levacor (World Heart Corp.)18 and HeartMate III (Thoratec Corp.)16,19 (Fig. 3). Again, there are general variations to this classification particularly with regards to the mechanism of impeller levitation. The application of magnetic levitation of the impeller for rotary blood pumps was reported by Akamatsu and colleagues in 199220,21 and by Allaire and colleagues in 1996.22
Rational for Development of 3rd Generation Rotary Pumps Device designs incorporating 2nd generation rotary pump technology with axial configuration have accumulated signif-
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Figure 4 DuraHeart left ventricular assist device: continuous-flow rotary pump with centrifugal design incorporating an external motor-drive system with magnetic levitation of the impeller. (A) Components of the DuraHeart system: upper housing containing the electromagnets and position sensors for primary levitation control of the impeller. Impeller with coupling magnets that permit the external motor-drive system (brushless DC motor) to rotate the impeller. Bottom housing containing the external motor-drive system. (Photograph courtesy of Dr. C. Nojiri, Terumo Corp., Ann Arbor, MI.) (B) Schematic of the DuraHeart left ventricular assist device. (Reprinted with permission from Hoshi et al.13) (Color version of figure is available online at http://www.semthorcardiovascsurg. com.)
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Figure 5 (A) Incor (Berlin Heart GmbH) left ventricular assist device incorporating axial design with magnetic levitation of the rotor. (B) Levitation and drive system schematic. (Reprinted with permission from Hoshi et al.13)
icant human clinical experience and are either currently in late stages of clinical trials in the United States or have recently been approved by the Food and Drug Administration (FDA) for bridge to transplant indication (Fig. 1).14,23,24 The 2nd generation rotary pumps have the advantage of a smaller pump size and potential for greater long-term mechanical reliability by elimination of the reservoir chamber and inflow and outflow valves needed for the 1st generation of pulsatile pump designs.14,23,24 Reports from clinical trials of the 2nd generation rotary pumps have demonstrated efficacy in providing hemodynamic support, a favorable risk to benefit assessment, and improvement in mechanical performance.14,24 Further, the human experience with 2nd generation rotary pumps with axial design has established the long-term safety of mechanical circulatory support with minimal pulse pressure.25,26 Results from clinical studies have demonstrated early improvement followed by long-term stability of renal and hepatic function and no adverse effects on neurocognitive performance.14,25,26 These improvements in device technology with the 2nd generation of continuous-flow rotary pumps with axial design have increased the acceptance of LVAD therapy for long-term mechanical circulatory support, although world-wide use of LVAD therapy for destination therapy still remains limited.
F.D. Pagani Although significant improvements in pump design have occurred with the 2nd generation of rotary pump with an axial blood flow path compared with the 1st generation of pulsatile devices, there remain a number of potential concerns with this technology. The presence of contact bearings to suspend the rotor represents a potential point of frictional wear resulting in device failure and subsequent need for device exchange.12,13 The 2nd generation rotary pumps with axial design still demonstrate the potential for thrombus formation on the device rotor and bearing interface due to the presence of stasis and incomplete bearing “wash.”14,23,27 However, the concern for development of thrombus on the rotor and bearing contact points has varied significantly with different 2nd generation rotary pumps.27 The presence of stators to suspend and redirect blood flow also represents an obstruction within the blood flow path. Thrombosis from blood stasis can be caused by blood flow disturbances and recirculating zones associated with the supports required by contact bearing design. Clinical studies have documented the problem with device thrombus requiring device exchange or treatment with thrombolytic therapy, and have also shown a reduced but persistent risk of stroke.14,27 A significant proportion of strokes reported during clinical trials with 2nd generation devices have occurred early following surgery and were associated with the implant procedure, likely representing air or particulate emboli possibly from sources other than the device. The proportion of strokes that are attributable to transient thrombus formation within the pump or thrombus formation within the heart is unknown. In addition, this technology still requires long-term antithrombotic therapy and, subsequently, hemorrhagic complications are observed with this therapy.14,23,24 An additional potential concern of 2nd generation rotary pumps with axial design is related to its hydrodynamic performance. To observe changes in pump flow at a fixed rotor speed, significant changes in pressure across the inlet and outlet orifices of the pump must occur.28,29 This relative degree of insensitivity of the hydrodynamic performance of the pump or “steep” pressure-flow relationship can result in left ventricular collapse and “suction” when filling pressures are abruptly reduced as in the case of a sudden onset of a ventricular arrhythmia, or result in elevated filling pressures with dyspnea when return to the left atrium is abruptly increased, as with exercise. Left ventricular collapse or “suction” event can, by itself, precipitate serious ventricular arrhythmias,30 and the inability to significantly increase pump flow with exercise may limit exercise performance in patients with axial pumps. However, the latter concern has not been observed in clinical exercise studies in humans.31 Algorithms for demand-responsive control for rotary pumps have been developed to overcome this perceived limitation in pump design.32
Design Features of 3rd Generation Continuous-Flow Rotary Pumps The persistent concern with limitations of the device technology of the 2nd generation of rotary pumps have led to further
Continuous-flow rotary LVADs improvements in device design leading to a 3rd generation of devices with continuous-flow rotary technology with centrifugal configuration and noncontact bearing design.12,13,15-18 The major advancement in design of the 3rd generation of rotary pumps has been the feature of magnetic and/or hydrodynamic levitation of the impeller with elimination of contact bearings within the pump.12,13,15-18 The elimination of contact bearings has the potential to significantly improve durability. The elimination of contact bearings along with magnetic levitation of the impeller results in a greater degree of blood flow around the suspended impeller and “washing” of the impeller that is perceived to be a major benefit in terms of reducing the risk of thrombus formation within the pump and perhaps reducing the intensity of antithrombotic therapy necessary with this technology.33 The 3rd generation of rotary pumps with centrifugal design have a more sensitive pressure-flow relationship compared with the 2nd generation of rotary pumps with axial design (Fig. 6).16,34 This greater sensitivity of the pressure-flow relationship in 3rd generation rotary pumps with centrifugal design results in greater changes in flow for any given change in pressure across the inlet and outlet orifices of the pump (Fig. 6). This greater pump response to changes in flow increases the margin of safety from creating suction events and improves pump flow during increases in left atrial return potentially enhancing exercise response. Further, the “flat” or sensitive pressure-flow characteristics of the 3rd generation of rotary pumps with centrifugal design increases the reliability of the estimated flow from pump power and rotor speed.35,36 In terms of its physical size, a 3rd generation rotary pump with full active magnetic-levitation of the impeller will never be as small as a 2nd generation rotary pump with axial design and mechanical bearing support of the rotor. However, the improvements in other design attributes of the 3rd generation of rotary pumps with centrifugal design, such as mechanical wear, operation at low flow, and perceived improved potential for hemocompatibility, while still maintaining a manageable size, warrant further clinical investigation.13 Whether these attributes of the 3rd generation of rotary pumps with centrifugal design will result in significant improvement in clinical outcomes over that observed with the 2nd generation of rotary pumps with axial design is not known at this time.
3rd Generation Rotary Pumps Currently in Clinical Evaluation VentrAssist The VentrAssist device (Ventracor Ltd.) is a continuous-flow rotary pump with centrifugal and noncontact bearing design. The device weighs 298 g, and measures 60 mm in diameter (Fig. 7).37,38 The operating range of the pump is 1,800 to 3,000 revolutions per minute (rpm) in the normal setting. The impeller is comprised of four small blades that are embedded with permanent magnets. The impeller blades act as a rotor for the pump’s brushless DC motor and spin when an electrical current is sequentially switched between three pairs of coils contained within the titanium housing of the pump.
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Figure 6 (A) Typical pressure-flow relations of the HeartMate III, 3rd generation centrifugal pump are compared with the HeartMate II, 2nd generation axial flow pump at two different speed ranges. The pressure-flow curves are similar at high flows, but the HeartMate III has a “flatter” relationship at lower flows. (Reprinted with permission from Farrar et al.16) (B) Demonstration of the greater sensitivity of the pressure-flow relationship of centrifugal-compared with axial-flow pumps. (Diagram courtesy of Dr. C. Nojiri, Terumo Corp., Ann Arbor, MI.)
Suspension of the impeller within the pump cavity is performed passively and is achieved entirely through the use of eight hydrodynamic bearings, one on each face of the four blades. No magnetic levitation is utilized in the levitation of the impeller. Dynamic interplay between the eight hydrodynamic bearing forces, fluid forces and gravitational forces prevents the spinning impeller from touching any part of the housing of the pump. The absence of magnetic levitation and monitoring systems to identify impeller position results in a less complicated electronics and smaller pump design. Clinical trials of the VentrAssist have been completed in Australia and Europe and are currently being conducted in the United States as part of a FDA-approved pivotal trial for both bridge to transplant and destination therapy indications.37,38 Initial clinical reports of the VentrAssist performance have demonstrated a satisfactory efficacy and risk profile of the device. Overall survival for 30 patients undergoing
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0.01 events per patient-month of support after 30 days. Device malfunctions included outflow graft leak (two), initial pump nonrestart following elective stop (one), inappropriate alarms (two), and accidental percutaneous lead transaction (one). As of January 30, 2007, a total of 87 patients have been implanted with the VentrAssist at 14 centers worldwide, yielding a total exposure time of more than 43 patient-years and a maximum implant duration of 2.7 years.
DuraHeart The DuraHeart (Terumo Corp.) is a continuous-flow rotary pump with centrifugal and noncontact bearing design (Figs. 4 and 8).13,17,34 The device has a displacement volume of 180 cm3 and a weight of 540 g. Its external dimensions are 72 mm in width and 45 mm in height. The pumping unit consists of an upper housing with the levitation system, impeller, and bottom housing containing the external-drive motor. The device is designed with active magnetic levitation of the impeller along with hydrodynamic bearings to support impeller levitation in case of failure of the magnetic levitation system. The impeller is rotated through magnetic coupling between permanent magnets embedded on the motor side of the impeller and an external-drive motor that utilizes a bearing design. Three electromagnets and three position sensors are mounted in the upper housing. Tilting and axial displacements of the impeller are monitored and controlled using a three degrees-of-freedom control. The ferromagnetic ring on the opposite side of the impeller is levitated by the electromagnet, and position sensors control the impeller so that it is always positioned at the center of the blood chamber. Radial impeller movement is passively suspended with a bias flux through electromagnetic rotor and drive magnet rotor.
Figure 7 (A) VentrAssist (Ventracor Ltd.) left ventricular assist device. (B) Internal view demonstrating the impeller that is comprised of four small blades that are embedded with permanent magnets. The impeller blades act as a rotor for the pump’s brushless DC motor and spin when an electrical current is sequentially switched between three pairs of coils contained within the titanium housing of the pump. (Photographs courtesy of Ventracor Ltd., Sydney, Australia). (Color version of figure is available online at http:// www.semthorcardiovascsurg.com.)
device implantation as a bridge to transplant was 86% at 22 weeks. At 22 weeks, 40% of patients had undergone heart transplantation, 13% of patients died while on device support, 3% of patients underwent device explantation for cardiac recovery, and 43% remained alive with ongoing device support. The most common protocol-defined, device-related serious adverse event was infection with 16 events occurring in 11 patients. The majority of infections occurred after 30 days. The rate of device-related infection within the first 30 days was 0.11 events per patient-month of support and 0.17 events per patient-month of support after 30 days. The occurrence of stroke was greatest in the first 30 days with an event rate of 0.18 events per patient-month of support and
Figure 8 DuraHeart Left Ventricular Assist Device. (Photograph courtesy of Dr. C. Nojiri, Terumo Corp., Ann Arbor, MI.)
Continuous-flow rotary LVADs Clinical evaluation of the DuraHeart device has recently concluded in Europe and clinical evaluation of the device in the United States is scheduled for 2008. A preliminary report of the European experience was recently presented at the International Society of Heart and Lung Transplantation in April of 2008.39 Thirty-five patients with advanced heart failure (NYHA class IV, 14 ischemic, 5 females), who were eligible for heart transplantation underwent implantation of the DuraHeart device from January of 2004 through September of 2007. Median age of the patients was 56 (range 29-73) years with a median body surface are of 1.9 (1.4-2.4) m2. The average duration of device support was 330 ⫾ 220 (17-808) days with a cumulative duration of 21 years. Fourteen patients (40%) underwent heart transplantation at 194 ⫾ 146 days. Nineteen patients (54%) were supported for at least 6 months and seven (20%) patients were supported for greater than 1 year. Fourteen patients (40%) remain alive with ongoing device support (330 ⫾ 292) days. Kaplan-Meier survival at 2 years was 78%. There were seven deaths (median time to deaths: 29 days). Six early deaths occurred for the initial 11 patients and four were associated with excessive anticoagulation/antiplatelet therapy that resulted in fatal intracerebral hemorrhage or subdural hematoma. After implementing less intensive anticoagulation and antiplatelet therapy comparable to mechanical heart valves, there was no ischemic or hemorrhagic stroke for the last 24 patients. Stroke-free survival for the last 24 patients was 94% at 2 years. Twenty-six patients (86% of 1 month survivors) were discharged home, and the readmission rate was 1.5/pt-y. There were no pump mechanical failures, pump thrombosis, or hemolysis throughout the support duration.
HVAD The HVAD (HeartWare Corp.) is a small continuous-flow rotary pump with centrifugal and noncontact bearing design (Fig. 9). The unique feature of the HVAD is its small design size.40,41 It has a displacement volume of 45 mL, and weighs 145 g with a flow capacity of up to 10 L/min. The device is small enough to place within the pericardial cavity without the need for dissection and creation of a preperitoneal pocket. The HVAD uses a wide-blade impeller design to maximize performance and hemocompatibility, size minimization, long-term reliability, and overall system efficiency. The impeller is suspended in place by combination of passive magnetic and hydrodynamic bearing systems to avoid mechanical contact and wear. The design integrates two motor stators for single-motor fault protection to increase reliability. The impeller suspension system uses a passive magnetic bearing for radial stiffness. Axial magnetic preload and hydrodynamic bearings on top of each impeller blade provide axial constraint. The magnetic bearing consists of a stack of rare earth ring magnets near the impeller’s inside diameter that repel the magnetic force of a similar stack of magnets inside the center post. The axial alignment of the center-post magnet stack is set to provide an axial force that pushes the impeller toward the forward housing (the assembly with the inflow cannula). Physical contact between the housing and
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Figure 9 HVAD (HeartWare Corp.). (Photograph courtesy of HeartWare Corp., Miami, FL.) (Color version of figure is available online at http://www.semthorcardiovascsurg.com.)
the impeller is prevented by a thin blood film generated by the hydrodynamic bearings. The hydrodynamic bearings feature a shrouded design that is intended to maximize the blood-film thickness and improve surface washing. The HVAD has undergone clinical evaluation in Europe and Australia and is scheduled to begin clinical evaluation in the United States in 2008. In a multi-institutional trial in Europe and Australia, 20 patients underwent implantation of the HVAD from March of 2006 through September of 2007.40 Mean age of the patients was 46 ⫾ 12 years (range 28-68 years). Median cardiopulmonary bypass time to implant the device was 67 min (range 21-140 min). Mean duration of HVAD device support was 167 ⫾ 143 days (range 13-425 days). Range of blood flow provided by the pump was 4.0-6.5 L/min. Three patients were successfully transplanted after 426, 349, and 157 days, respectively. One patient was weaned from pump support on postoperative day 266, two patients died on device (postoperative days 13 and 203), and 14 patients remain alive with ongoing device support. Actuarial survival at 1 year was 80%.
Levacor The Levacor device (World Heart Corp.) is a continuous-flow rotary pump with centrifugal and noncontact bearing design (Fig. 10).13,18,42 The pump is 35-mm high and 75 mm in diameter. Its weight is 440 g with 22-mL priming volume. The magnetic levitation system utilizes a combination of permanent magnets that provide passive levitation, and a magnet coil that provides active levitation along one degree-offreedom of movement of the impeller. To minimize power consumption, the passive and active levitation elements function together, permitting the passive levitation to counteract almost all of the mechanical force on the rotor. This is done using a method of control known as virtual zero power control.13,18,42 Aside from rotation, the other five degrees-of-
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were transplanted, 11 (5%) were explanted (weaned from the system), 43 (20%) remain alive with ongoing pump support, and 93 (44%) of patients died on the system. The major cause of death was multiorgan failure in 47 (22%) patients followed by cerebrovascular events in 17 cases. Other causes of death were right ventricular failure, five cases (2%); trauma, two cases (1%); cancer, three cases (1%); and others or unknown, 20 cases (9%). Fifty-one patients (21%) were discharged home on the device. There were no deaths related to device failure.
Summary
Figure 10 Levacor left ventricular assist device (World Heart Corp.). (Figure courtesy of World Heart Corp., Oakland, CA.)
freedom of movement of the pump rotor are all passively controlled except axial movement in the z-direction, which is actively controlled by the coil and electronics. The motor is integrated directly into the pump housing and rotor and no external motor is required for rotation. Clinical evaluation of the Levacor device has been initiated in Europe and Canada with successful results reported in a bridge to recovery protocol.42 Clinical evaluation in the United States is scheduled for 2008.
Incor The Incor (Berlin Heart GmbH) is an example of a continuous-flow rotary pump with axial design and magnetic levitation of the rotor using a direct-drive mechanism (Fig. 5).13,15,43-45 The pump weighs 200 g, has an axial direction of 120 mm, an outer diameter of 30 mm, and a volume of 80 mL. Axial impeller movement is monitored by a position sensor and controlled actively by the two electromagnets mounted at both ends of the rotor. Radial and tilting impeller movements are passively controlled. The levitated impeller can be rotated at speeds between 5,000 and 10,000 rpm generating up to 5 L/min of flow against a pressure of 100 mm Hg with a magnetic levitation power consumption of 2 to 4 W. The motor efficiency of more than 90% and power consumption ⬍4 W ensure that the pump does not generate any significant amount of heat. The control software enables monitoring of the pressure gradient and the flow by detection of the rotor’s position in the magnetic field. The flow straighter and diffuser are adapted for inflow and outflow passage, respectively, to reduce the spin of blood flow and add to the pressure buildup. All blood-contacting surfaces are heparin coated by the Carmeda process. Clinical evaluation of the Incor device was initiated in Europe in June of 2002 with a total of 212 implants reported worldwide.13,15,41,42,43 The mean patient age was 51.5 ⫾ 13 years (range 16-72 years), and 24 patients (11.3%) were female. The mean duration of support on the device was 162 ⫾ 182 days (maximum: 1071 days). Sixty-five (31%) patients
Third generation, continuous-flow pumps with noncontact bearing design offer the potential of enhanced durability and safety for extended mechanical circulatory support. Early clinical experience with these devices demonstrate efficacy with regard to hemodynamic support. Further clinical evaluation will be necessary to determine if the improved hydrodynamic properties of centrifugal pumps and potential enhanced durability of a noncontact bearing design are associated with improvements in patient outcomes.
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