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A review of clinical ventricular assist devices
Medical Engineering & Physics 33 (2011) 1041–1047
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Medical Engineering & Physics journal homepage: www.elsevier.com/locate/medengphy
A review of clinical ventricular assist devices Daniel Timms a,b,c,∗ a
ICET Laboratory, Critical Care Research Group, The Prince Charles Hospital and University of Queensland, Brisbane, Australia Applied Medical Engineering, The Helmholtz Institute, Aachen, Germany c Dept. of Cardiovascular Engineering, Inst. for Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany b
a r t i c l e
i n f o
Article history: Received 5 June 2010 Received in revised form 18 April 2011 Accepted 23 April 2011 Keywords: Artificial organs Ventricular assist device Rotary blood pump
a b s t r a c t Given the limited availability of donor hearts, ventricular assist device (VAD) therapy is fast becoming an accepted alternative treatment strategy to treat end-stage heart failure. The field of mechanical ventricular assistance is littered with novel and unique ideas either based on volume displacement or rotary pump technology, which aim to sufficiently restore cardiac output. However, only a select few have made the transition to the clinical arena. Clinical implants were initially dominated by the FDA approved volume displacement Thoratec HeartMate I, IVAD, and PVAD, whilst Berlin Heart’s EXCOR, and Abiomed’s BVS5000 and AB5000 offered suitable alternatives. However, limitations associated with an inherently large size and reduced lifetime of these devices stimulated the development and subsequent implantation of rotary blood pump (RBP) technology. Almost all of the reviewed RBPs are clinically available in Europe, whilst many are still undergoing clinical trial in the USA. Thoratec’s HeartMate II is currently the only rotary device approved by the FDA, and has supported the highest number of patients to date. This pump is joined by MicroMed Cardiovascular’s Heart Assist 5 Adult VAD, Jarvik Heart’s Jarvik 2000 FlowMaker and Berlin Heart’s InCOR as the axial flow devices under investigation in the USA. More recently developed radial flow devices such as WorldHeart’s Levacor, Terumo’s DuraHeart, and HeartWare’s HVAD are increasing in their clinical trial patient numbers. Finally CircuLite’s Synergy and Abiomed’s Impella are two mixed flow type devices designed to offer partial cardiac support to less sick patients. This review provides a brief overview of the volume displacement and rotary devices which are either clinically available, or undergoing the advanced stages of human clinical trials. © 2011 Published by Elsevier Ltd on behalf of IPEM.
Contents 1. 2.
3.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042 Volume displacement pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042 2.1. Thoratec “HeartMate I” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042 2.2. Thoratec “IVAD/PVAD” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 2.3. Berlin Heart “EXCOR” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 2.4. Abiomed “AB5000 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 Rotary pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 3.1. Axial flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 3.1.1. Thoratec “HeartMate II” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.1.2. Jarvik Heart “Jarvik 2000 FlowMaker” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.1.3. MicroMed Cardiovascular “Heart Assist 5 Adult VAD” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.1.4. Berlin Heart “InCOR” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.2. Radial flow (centrifugal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045 3.2.1. WorldHeart “Levacor” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045 3.2.2. Terumo “DuraHeart” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045
∗ Corresponding author at: ICET Laboratory, Critical Care Research Group, The Prince Charles Hospital and University of Queensland, Brisbane 4032, Australia. Tel.: +61 7 3139 4630; fax: +61 7 3856 7330; mobile: +61 438567330. E-mail address: [email protected] 1350-4533/$ – see front matter © 2011 Published by Elsevier Ltd on behalf of IPEM. doi:10.1016/j.medengphy.2011.04.010
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3.2.3. HeartWare “HVAD” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045 Mixed flow (diagonal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 3.3.1. CircuLite synergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 Conflict of interest statement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 3.3.
4.
1. Introduction Ventricular assist devices are employed clinically to help ease the rising demand for heart donors. These devices may be used to support a failing left and/or right ventricle, whilst being implemented as abridge to decision (BTD), bridge to myocardial recovery (BTR), bridge to heart transplantation (BTT), or indeed as a longer term destination therapy (DT) for patients in need of circulatory support. History has witnessed the development of many types of circulatory assist devices. Efforts were initially focused on devices that reproduce the pulsatile outflow delivered by the native heart [1,2]. Despite the improved one-year survival observed when treated with these devices over optimal medical therapy [3], these types were inherently flawed with reliability and durability problems, by virtue of their mode of operation. These issues led to a push to develop continuous flow devices based on a rotating impeller [4–6], which has resulted in improved outcomes for patients treated with these devices [7]. Mechanical circulatory assist devices are generally classified according to their characteristic outflow (pulsatile/volume displacement or continuous) as described in Table 1, with details relating to their operational characteristics categorising them further into first, second or third generation designs [8]. Another additional classification is emerging which categorises the devices as either providing partial or full circulatory support for short or long-term durations. The distinction indicates the target patient population, with partial support devices, often implanted via minimally invasive techniques, intended for use in less sick patients. This review provides an overview of the various types of mechanical ventricular assist devices which enable patient mobility for greater than 30 days, and are either clinically available or undergoing clinical trials to gain food and drug administration (FDA) approval. 2. Volume displacement pumps Although pumps that deliver a pulse to the circulatory system produce a similar physiologic outflow to that of the human heart, they are generally volume displacement type devices that incorporate pneumatically or electrically actuated sacs, diaphragms or pusher plates. These pumps, classified as ‘first generation’, have an inherently large tissue and blood contacting surface and have multiple moving mechanical parts including prosthetic valves. Despite advancements in affiliated technologies, these features limit the effectiveness of first generation devices as they are both difficult to fit into many patients and are prone to mechanical failure due to wear inside two or three years [9]. Furthermore, they present a high risk of infection, thrombus formation and blood trauma, which also contribute to poor patient outcomes [10]. Despite these limitations, pulsatile pumps were aggressively developed in the last century and as a result, many of these devices became clinically available to provide full mechanical circulatory support. These more commonly known and commercially available pumps are produced by companies such as Thoratec, Berlin Heart and Abiomed.
Fig. 1. HeartMate I XVE.
2.1. Thoratec “HeartMate I” The HeartMate I LVAS series evolved from the discontinued implantable pneumatic (IP) model to the vented electric VE and finally the XVE (Fig. 1) [11,12]. Both devices are medium to long term first generation volume displacement pumps. They rely on the actuation of a pusher plate that interfaces with a flexible plastic diaphragm to induce pulsatile blood flow from the left ventricular apex to the ascending aorta [13]. However, as the name suggests, the HeartMate IP was pneumatically powered, whilst the XVE utilises an electric power source to shift the pusher plate. It is for this reason that the XVE replaced its predecessor as the model of choice, since the electric supply reduces the size of the skin penetrating driveline to just ∅ 12 mm, whilst eliminating the requirement for an external compressed air source. With a size of ∅ 110 × 40 mm and weight of 1190 g, the device exhibits a somewhat restricted ability for intra-corporeal implantation into patients with a body surface area (BSA) smaller than 1.5 m2 . However, full support of up to 10 l/min is achievable at a maximum beat rate of 120 BPM. The sintered titanium blood contacting surfaces reduce the requirement for anticoagulation therapy by promoting the formation of a pseudo neo-intima lining [14]. The HeartMate XVE was involved in a randomised study (REMATCH) which demonstrated that patients exhibited an 81% improvement in two year survival with this device as opposed to Table 1 Types of clinical ventricular assist devices. Volume displacement
Rotary – Axial Flow
Rotary – Radial Flow
Rotary – Mixed Flow
Thoratec ‘HeartMate I XVE/IP’ Thoratec ‘IVAD/PVAD’ Abiomed ‘BVS5000/AB5000’ Thoratec ‘HeartMate II’ Jarvik Heart ‘Jarvik 2000 FlowMaker’ MicroMed ‘Heart Assist 5 Adult VAD’ Berlin Heart ‘InCOR’ WorldHeart ‘Levacor’ Terumo ‘DuraHeart’ HeartWare ‘HVAD’ Abiomed ‘Impella’ CircuLite ‘Synergy’
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The Berlin Heart EXCOR attained CE mark prior to 2000, and has been available for paediatric use since 2008 due to an FDA approved unconditional investigational device exemption (IDE). More than 2000 devices have been implanted worldwide to date. 2.4. Abiomed “AB5000
Fig. 2. IVAD. (Courtesy of Thoratec Corp.)
optimal medical therapy [3]. This reported success, coupled with FDA approval for DT in 2003, led to HeartMate I support in more than 4500 patients in 186 centres worldwide. 2.2. Thoratec “IVAD/PVAD” The Thoratec PVAD and IVAD are pneumatically operated first generation devices designed for short to medium term left/right or biventricular support [15]. The PVAD is a paracorporeal device that was FDA approved for BTTin 1995 and BTR postcardiotomy support in 1998, whilst the implantable IVAD (Fig. 2) was approved in 2004. Both devices maintain the same blood flow path, valves and polyurethane blood pump sac, which can deliver up to 6.5 l/min (PVAD) and 7.2 l/min (IVAD) when actuated at the maximum rate of 100 BPM. The polyurethane surface requires the chronic administration of anticoagulation therapy such as warfarin to maintain an international standard ratio (INR) of 2.0–3.0 at all times [16]. The major difference between the models, other than the semirigid polyurethane (PVAD) and titanium (IVAD) housing, is the slightly smaller size and weight (125 mm × 80 mm × 50 mm and 339 g) of the IVAD compared to the PVAD (125 mm × 80 mm × 60 mm and 417 g). This ultimately allows implantation in patients ranging from 40 to ≥100 kg or with a BSA > 1.3 m2 . Only the IVAD pump is implanted in a pre-peritoneal position with a small (∅ 9 mm) percutaneous pneumatic drive line connected to a more complex external control unit. Despite the implantability, only about 560 patients have been supported by the IVAD, compared to more than 4400 patients with the PVAD. The paracorporeal connection of the PVAD may make pump exchanges easier in the face of device malfunction or adverse events, which may explain the differences in these numbers. Furthermore, the earlier FDA approval of the PVAD provided a longer duration of clinical availability. 2.3. Berlin Heart “EXCOR” The Berlin Heart EXCOR device is a first generation, pneumatically actuated, paracorporeal VAD capable of left, right or biventricular support in adult or paediatric patients [17]. The device has a range of scale versions, with adult pumps available in 50, 60 and 80 ml sizes, whilst paediatric pumps have volumes of 10, 20 and 35 ml [18]. A maximum of 10 l/min can be delivered from the largest pump at a maximum beat rate of 150 BPM. The pump chambers are transparent polyurethane and all blood contacting surfaces are coated with heparin. However, a coagulation regime of warfarin, aspirin and dipyridamole is still recommended to maintain a relatively high INR between 3 and 3.5 [19].
The Abiomed AB5000 is a paracorporeal, pneumatically driven, first generation, volume-displacement pump, specifically designed for patient ambulation and longer support duration than the BVS5000. It too relies on a compressed air source to actuate a flexible polyurethane diaphragm contained in a relatively light (230 g) transparent pump chamber. It can be also be connected in a uni- or bi-ventricular fashion to treat cardiogenic or postcardiotomy shock, and can act alone or as a replacement for an Abiomed BVS5000 without requiring additional surgery. Despite approval by the FDA in 2003 for BTR, only a small number of the AB5000 pumps have been implanted to date [21,22]. 3. Rotary pumps Despite initial scepticism within the medical community, continuous flow type devices are now accepted for use in mechanical circulatory assist therapy. Although concerns regarding the long term physiological effects of ‘non-pulsatile’ support remain, the distinct advantages of small size and superior mechanical longevity have accelerated acceptance of this form of therapy over traditional pulsatile devices. In cases of remaining cardiac contractility, some degree of pulsatility remains under normal operation, as the inlet pressure to the pump is cyclical according to the cardiac cycle phase of the native left ventricle to which it is often connected. Furthermore, the level of electrical power needed to operate these devices results in a relatively small driveline, which acts to reduce the incidence of device related infection. The number of patients ultimately supported with this form of technology is increasing, and studies have appeared that demonstrate improvements in patient outcomes when compared to earlier volume displacement devices [7]. Devices in this category produce their characteristic partial or full support continuous flow via a rotating impeller housed within a small pump chamber, without the need for directional valves. This impeller can be termed axial, radial (centrifugal), or mixed flow, and refers to the direction to which the blood enters and leaves the impeller. These rotary pumps formed the beginning of the second generation of devices, characterised by a contact shaft/roller bearing/seal or blood immersed (pivot) bearing impeller support mechanism. Whilst these devices have proven capable of supporting the circulation, the remaining mechanical contact is thought to impose a serious contraindication for long term use in excess of five years [23]. Several techniques have since been proposed to solve this concern, which gave rise to the latest, third generation of devices. These systems effectively eliminate mechanical contact and thus wear by completely suspending the rotating impeller using magnetic or hydrodynamic forces, potentially increasing device lifetime beyond ten years [24]. Many cardiovascular device manufacturers have understood the advantages of the rotary/continuous flow approach and as such have invested considerable resources into developing suitable devices. 3.1. Axial flow Axial flow rotary blood pumps are small and contain an impeller that can spin at speeds between 6000 and 15,000 rpm to deliver blood flow to the circulatory system. Owing to their small size, most axial flow devices are limited to second generation pumps, however, third generation technology has also been utilised in one
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Since the initiation of clinical trials in July 2000, and FDA approval for BTT in 2008 and DT in 2010, more than 5000 patients worldwide have been implanted with the device. The HeartMate II was also instrumental in a recent study which advocated superior results in patients receiving non-pulsatile type mechanical circulatory support [7].
Fig. 3. Heart Assist 5. (Courtesy of Jarvik Heart Inc.)
instance [25]. The required impeller peripheral velocity is higher than other rotary type devices, which may contribute to relatively higher shear stress development and thus levels of haemolysis and platelet activation. Furthermore, the need for stationary guide vanes and a contact impeller suspension may promote thrombus formation in areas of recirculation or stagnation. Finally, due to the combination of a high rotational speed and contact pivot bearing support mechanism, the service life of axial flow pumps is predicted at below five years. However, there have been reported instances of longer support [26]. All axial flow devices are capable of providing full circulatory support. Manufacturers Thoratec Corporation, Jarvik Heart, MicroMed Cardiovascular, and Berlin Heart are leading the field, with all possessing CE mark approval. At this stage, only the HeartMate II is approved by the FDA, however, other devices are nearing their IDE trial endpoints and submission for BTT status should follow soon. Helped by its regulatory status, the HeartMate II device has been implanted in up to 10 times more patients than any other rotary device.
3.1.1. Thoratec “HeartMate II” The HeartMate II (Fig. 3) is an implantable, second generation, axial flow pump that provides full circulatory support (up to 10 l/min) to left heart failure patients. The small device (∅ 40 × 60 mm), approximately the size of a D-Cell battery, weighs 375 g and incorporates an electromagnetic DC brushless motor to provide rotation to the dual cup-socket ruby bearing supported impeller which has demonstrated a five year service life. Operating speeds between 6000 and 15,000 rpm are possible, with suitable haemodynamic pressures and flows typically produced at 9000 rpm [27,28]. Redesigns of the pivot bearing area have ensured that it is well washed, in an attempt to limit thrombus formation. However, somewhat paradoxically, anticoagulation therapy has been reduced in these patients to maintain a low INR of just 1.5–2.0 [29]. It has been suggested that acquired von Willebrand syndrome caused by shear stresses in the device may play a role in this observation [30].
3.1.2. Jarvik Heart “Jarvik 2000 FlowMaker” The Jarvik 2000 FlowMaker is a long term implantable, full support, second generation, axial flow pump that resides in the ventricular cavity and circulates blood to the ascending or descending aorta [31]. Whilst predominately used for left ventricular assistance, owing to the small size and weight (∅ 25 × 55 mm and 85 g), a few clinical cases have been reported of right [32] or biventricular assistance [33]. The impeller, supported at each end by tiny blood-immersed ceramic bearings, constitutes the only moving part of the device, which can deliver flow rates of 3–7 l/min at 8000–12,000 rpm [28]. These bearings require the patient to chronically maintain a warfarin induced INR of 2.5–3.5 [34]. No implantable components have failed throughout the clinical experience of more than 357 patients since the first implant in April 2000. Despite the mechanical contact impeller support, one patient was supported for more than seven years [35]. A low risk of infection is also apparent in DT patients, which is due in part to the delivery of power via a small post auricular pedestal [36]. However, a more conventional exit from the sub costal margin is often selected in BTT patients. 3.1.3. MicroMed Cardiovascular “Heart Assist 5 Adult VAD” The MicroMed Heart Assist 5 LVAD is a miniaturised, implantable, second generation, axial flow pump capable of long term circulatory support for left heart failure [37]. The electromagnetically driven pump weighs 95 g, and is ∅ 25 × 86 mm in dimension. The pump connects the left ventricle (LV) apex to the ascending aorta, and pumps 5–6 l/min at 10,000 rpm, with flows of over 10 l/min possible when operated at a maximum speed of 12,500 rpm. These flow rates are measured directly with an ultrasonic flow probe placed around the outflow graft, a feature unique to this device. The impeller is supported with front and back mechanical pivot bearings, incorporated in the flow straightening inducer and stationary outlet diffuser. The durability of the contact bearing has proven to exceed two years. Cameda® biocompatible coating is applied to the blood contacting surfaces in an attempt to limit the incidence of thrombus formation, which plagued earlier iterations of this device. Subsequent iterations have addressed this concern, with the patient required to maintain an INR of 2.5–3.5 via coumarin [28,38]. Clinical trials were initiated in 1998, with more than 440 implants taking place since, significantly less than the more recently developed HeartMate II device. CE mark approval for the adult VAD was attained in 2010, whilst a humanitarian device exemption (HDE) was awarded by the FDA in 2005 for a paediatric version of the device. 3.1.4. Berlin Heart “InCOR” The InCOR left ventricular assist device (Fig. 4) is a long term, implantable, third generation, axial flow pump that circulates blood from the LV apex to the ascending aorta in left heart failure patients [39]. Complete rotor suspension is achieved with active axial electromagnetic bearings positioned at each end of the rotor, which passively constrain radial movement and tilting of the rotor. At a size of ∅ 30 × 120 mm, it is the largest of the axial flow devices, whilst its magnetic system contributes to its device weight of 200 g [40].
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Fig. 4. Incor. (Courtesy of Berlin Heart GmbH.)
The device includes a stationary inlet inducer and outlet diffuser which assist the rotor to produce 5 l/min at 8000 rpm, with a maximum flow rate of 7 l/min achievable with speeds of 10,000 rpm [28]. A unique control algorithm is implemented to determine pump performance characteristics. Using the magnetic bearing configuration, the rotor position is measured in the magnetic field, which is then used to control the pump speed [41]. All blood-contacting surfaces are heparin coated with Carmeda® to improve biocompatibility. An anticoagulation strategy using clopidogrel or dipyridamole has been reported to maintain an INR of 2.5–3.0 [42]. Thromboembolic related neurologic complications were observed in early clinical applications. However, a modified inlet cannula, which protruded a further 10 mm into the left ventricular cavity, significantly reduced these adverse events [42]. The first human clinical trial occurred in June, 2002 and following CE mark approval in 2003, more than 500 implants worldwide have since taken place. The device is, however, unavailable in the USA at this time. 3.2. Radial flow (centrifugal) Whilst slightly larger in diameter than axial flow devices, radial flow (centrifugal) pumps are suitable for long term cardiac assistance due to their lower corresponding rotational speed, higher hydraulic efficiency (for blood pump applications), elimination of stationary vanes and a more anatomically suitable flatter shaped profile. Furthermore, due to their rotor geometry and increased surface area, these pumps can take advantage of the third generation bearing technology to completely suspend the impeller using hydrodynamic or magnetic bearing forces. This effectively eliminates component wear, potentially increasing device lifetime to beyond ten years. All radial flow devices provide full circulatory support, with manufacturers WorldHeart, Terumo, and HeartWare developing devices that have either received a CE mark in Europe or are undergoing clinical trials for FDA approval in the USA. Implant numbers of this latest generation technology do not currently match previous generation devices; however, the HeartWare HVAD is rapidly increasing in numbers, with implantations already surpassing all previous rotary devices bar the HeartMate II, in just a few years. 3.2.1. WorldHeart “Levacor” The Levacor LVAD, formerly ‘Heartquest’, is a long term, implantable, third generation, radial flow pump that integrates a hybrid active and passive magnetic bearing to completely suspend a centrifugal impeller [43]. Designed for left ventricular assistance in BTT and DT applications, the device has also been used for BTR [44]. Although heavier (440 g) and larger in size (∅ 75 × 35 mm) than all axial flow rotary pumps [45], complete suspension eliminates device lifetime limiting wear. This device can produce flows ranging
Fig. 5. DuraHeart. (Courtesy of Terumo Heart Inc.)
from 0 to 10 l/min, with 5 l/min achievable with a rotational speed of around 2000 rpm. The lower flow rate is advantageous when weaning the patient in BTR applications, however, may increase the potential for thrombus formation in the pump. The polished titanium blood contacting surfaces attempts to limit thrombotic events in cooperation with an anticoagulation strategy targeting a relatively high chronic INR of 3.0–3.5 with aspirin/clopidogrel/dipyridamole. The Levacor is currently an investigational device in the USA, limited by the FDA for bridge to transplant applications. Clinical evaluation began in 2006 [46], with only ∼17 patients supported by the device to date. Regulatory trials are underway in the USA (BTT) and Europe. 3.2.2. Terumo “DuraHeart” The DuraHeart LVAD (Fig. 5) is an implantable, third generation, radial flow pump that incorporates an axial magnetic bearing (MB) to provide long term left ventricular assistance with a contact-free impeller suspension system [47]. The device is the largest and heaviest of the rotary pumps, with a size of ∅ 72 × 45 mm and weight of 540 g [48]. However, the relatively large (250 m) clearance gaps, characteristic of MBs, have the potential to reduce blood trauma. An external brushless DC motor achieves impeller rotational speeds from 1200 to 2600 rpm via a direct coupled magnetic drive to provide full circulatory support between 2 and 10 l/min. A backup spiral groove hydrodynamic bearing is incorporated into the titanium housing between the motor and the rotor to provide continued non-contact suspension should the primary magnetic bearing system fail. The blood contacting titanium surfaces benefit from a covalently bonded heparin coating to prevent thrombosis formation in the pump interior. This is further enhanced by a chronic anticoagulation regime of warfarin that achieves an INR of 2.5–3.0. Clinical implants of the DuraHeart started in January 2004, with CE approval attained in 2007. The large device size and resulting inflow cannula placement difficulties, however, have restricted device implants to just over 118 patients to date. 3.2.3. HeartWare “HVAD” The HeartWare HVAD (Fig. 6) is a third generation, radial flow pump, implanted in the pericardial cavity. The HVAD draws blood from an integrated inflow cannula inserted directly into the ventricular cavity. Initially designed for left ventricular assistance, the device has also been modified for bi-ventricular assistance [49,50], however, no studies have methodically evaluated the appropriateness of this approach. The single rotating impeller is completely suspended via a combination of passive magnetic and hydrodynamic forces created via a tapered thrust axial bearing [23,51]. The device is the smallest
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D. Timms / Medical Engineering & Physics 33 (2011) 1041–1047
Fig. 6. HVAD. (Courtesy of Heartware International Inc.)
(∅ 50 mm) and lightest (145 g) of the radial flow pumps. The dual flat axial flux motor arrangement rotates the impeller at a typical speed of 2400 rpm, whilst speeds between 1800 and 4000 rpm are possible, delivering up to 10 l/min [51]. The dual motor provides a level of redundancy. The lower speed limit ensures the continued generation of sufficient hydrodynamic lift to maintain stable impeller levitation. A ceramic–titanium blood contacting surface is used to mitigate thrombus formation inside the pump. Achieving a chronic INR of 2.5–3.0 with warfarin also helps to maintain thrombus free operation [52]. Clinical trials of the HVAD device began in 2008, with more than 700 patients now implanted worldwide. CE mark was attained in 2009, and an IDE BTT trial was completed in 2010 for submission to the FDA. 3.3. Mixed flow (diagonal) As the name suggests, mixed flow devices are a mixture between axial and centrifugal flow pumps. Fluid enters axially whereby it is pumped diagonally, collected, and distributed radially. The impeller is relatively difficult to completely suspend, thus mixed flow devices are generally based on second generation support techniques. The only mixed flow device that is undergoing clinical trial, is manufactured by CircuLite. 3.3.1. CircuLite synergy The Synergy Pocket Circulatory Assist Device (Fig. 7) is a new concept ventricular assist device that is intended to provide partial left ventricular circulatory support for patients classified with NYHA class III heart failure/INTERMACS 4+ [55].
Fig. 7. Synergy. (Courtesy of Circulite Inc.)
The miniature device is the smallest and lightest medium to long term, rotary pump in the clinical arena, measuring just ∅ 12 × 50 mm in its initial prototype form and weighing 25 g [56]. These features allow the device to be implanted into the pacemaker pocket via a less invasive left thoracotomy [57,58]. The unique anatomical connection sees the inflow cannulating the left atrium (LA), with the outflow directed to a peripheral artery (e.g. subclavian artery) [59]. This method of cannulation reduces the typical left ventricular apical trauma associated with conventional LVAD insertion whilst also reducing the workload of the heart, thus providing a suitable environment for BTR applications. A pivot bearing supported mixed flow impeller, contained in the titanium housing, is rotated at 20,000–28,000 rpm to provide 2–3.5 l/min of partial support. This lower flow however is of concern for pump thrombus formation [60], and may be a factor contributing to the high rate of pump exchanges required in an initial pilot study of the device, despite a suitable anticoagulation strategy that maintained an INR of 2.5–3.0 [61]. A clinical CE mark trial of the device began in 2007 in Europe and has so far been implanted in at least 27 patients. 4. Conclusion The improved clinical results of end stage heart failure patients treated with mechanical circulatory support therapy over medically managed patients has driven the acceptance of ventricular assist device technology by the medical community. Despite the initial clinical dominance of volume displacement type devices, their inherent limitations have driven VAD developers toward smaller, more reliable, rotary pump technology. This has resulted in the clinical investigation and/or availability of numerous axial, centrifugal or diagonal type devices, which have been shown to produce superior clinical results when compared to their volume displacement predecessors. Continued clinical experience with these devices will no doubt improve patient outcomes, propelling more devices into the clinical arena, which will expand the numbers of patients treated with this life saving technology. Conflict of interest statement The author has no conflict of interest that would influence the content of this manuscript. References [1] Guy T. Evolution and current status of the total artificial heart: the search continues. ASAIO J 1998;44:28–33. [2] Copeland J, Smith R, Arabia F, Nolan P, Mehta V, McCarthy M, et al. Comparison of the cardiowest total artificial heart, the novacor left ventricular assist system and the thoratec ventricular assist system in bridge to transplantation. Ann Thorac Surg 2001;71:S92–7. [3] Rose E, Gelijns A, Moskowitz A, Heitjan D, Stevenson L, Dembitsky W, et al. Long-term use of a left ventricular assist device for end stage heart failure. N Engl J Med 2001;345:1435–43. [4] Maslen EH, Bearnson GB, Allaire PE, Flack RD, Baloh M, Hilton E, et al. Feedback control applications in artificial hearts. IEEE Control Syst Mag 1998;18:26–34. [5] Kung RTV, Hart RM. Design considerations for bearingless rotary pumps. Artif Organs 1997;21:645–50. [6] Meyns B. Ventricular support with miniature rotary blood pumps. Leuven University Press; 1997. [7] Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 2009;361:2241–51. [8] Yamane T. The present and future state of nonpulsatile artificial heart technology. J Artif Organs 2002;5:149–55. [9] Maslen EH, Bearnson GB, Allaire PE, Flack RD, Baloh M, Hilton E, et al. Artificial hearts. In: Proceedings of the 1997 IEEE international conference on control applications. 1997. p. 204–9. [10] Frazier O, Rose E, Macmanus Q, Burton N, Lefrak E, Poirier V, et al. Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device. Ann Thorac Surg 1992;53:1080–90.
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[38] Wieselthaler GM, Schima H, Hiesmayr M, Pacher R, Laufer G, Noon GP, et al. First clinical experience with the DeBakey VAD continuous-axial-flow pump for bridge to transplantation. Circulation 2000;101:356–9. [39] Christiansen S, Perez-Bouza A, Reul H, Autschbach R. In vivo experimental testing of a microaxial blood pump for right ventricular support. Artif Organs 2006;30:94–100. [40] Pagani FD. Continuous-flow rotary left ventricular assist devices with “3rd generation” design. Semin Thorac Cardiovasc Surg 2008;20:255–63. [41] Arndt A, Nüsser P, Graichen K, Müller J, Lampe B. Physiological control of a rotary blood pump with selectable therapeutic options: control of pulsatility gradient. Artif Organs 2008;32:761–71. [42] Schmid C, Jurmann M, Birnbaum D, Colombo T, Falk V, Feltrin G, et al. Influence of inflow cannula length in axial-flow pumps on neurologic adverse event rate: results from a multi-center analysis. J Heart Lung Transpl 2008;27:253– 60. [43] Bearnson GB, Olsen DB, Khanwilkar PS, Long JW, Sinnott M, Kumar A, et al. Implantable centrifugal pump with hybrid magnetic bearings. ASAIO J 1998;44:M733–6. [44] Pitsis AA, Visouli AN, Ninios V, Bougioukas G, Filippatos G, Kremastinos D, et al. Elective bridging to recovery after repair: the surgical approach to ventricular reverse remodeling. Artif Organs 2008;32:730–4. [45] Bearnson GB, Jacobs GB, Kirk J, Khanwilkar PS, Nelson KE, Long JW. HeartQuest ventricular assist device magnetically levitated centrifugal blood pump. Artif Organs 2006;30:339–46. [46] Pitsis A, Visouli A, Vassilikos V, Ninios V, Sfirakis P, Mezilis N, et al. First human implantation of a new rotary blood pump: design of the clinical feasibility study. Hellenic J Cardiol 2006;47:368–76. [47] Hoshi H, Shinshi T, Takatani S. Third-generation blood pumps with mechanical noncontact magnetic bearings. Artif Organs 2006;30:324–38. [48] Nishinaka T, Schima H, Roethy W, Rajek A, Nojiri C, Wolner E, et al. The DuraHeart VAD, a magnetically levitated centrifugal pump. The university of vienna bridge-to-transplant experience. Circ J 2006;70:1421–5. [49] Hetzer R, Krabatsch T, Stepanenko A, Hennig E, Potapov E. Long-term biventricular support with the heartware implantable continuous flow pump. J Heart Lung Transpl 2010;29:822–4. [50] Strueber M, Meyer A, Malehsa D, Haverich A. Successful use of the HeartWare HVAD rotary blood pump for biventricular support. J Thorac Cardiovasc Surg 2010, eprint. [51] LaRose JA, Tamez D, Ashenuga M, Reyes C. Design concepts and principle of operation of the heartware ventricular assist system. ASAIO J 2010;56: 285–9. [52] Wieselthaler GM, O’Driscoll G, Jansz P, Khaghani A, Strueber M. Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial. J Heart Lung Transpl 2010;29: 1218–25. [55] Krishnamani R, DeNofrio D, Konstam MA. Emerging ventricular assist devices for long-term cardiac support. Nat Rev Cardiol 2010;7:71–6. [56] Kerkhoffs W, Schumacher O, Meyns B, Verbeken E, Leunens V, Bollen H, et al. Design, development, and first in vivo results of an implantable ventricular assist device, MicroVad. Artif Organs 2004;28:904–10. [57] Meyns B, Ector J, Rega F, Droogne W, Vanhaecke J, Vanhemelrijck J, et al. First human use of partial left ventricular heart support with the CirculiteTM synergyTM micro-pump as a bridge to cardiac transplantation. Eur Heart J 2008;29:2582. [58] Meyns B, Rega F, Ector J, Droogne W, Vanhaecke J, Van Hemelrijck J, et al. Partial left ventricular support implanted through minimal access surgery as a bridge to cardiac transplant. J Thorac Cardiovasc Surg 2009;137:243–5. [59] Meyns B, Verbeken E, Kerkhoffs W, Bethuyne N, Bakir I, Marseille O, et al. Partial support for chronic heart failure with a subcutaneous pump. J Heart Lung Transpl 2006;25:s123–4. [60] McCarthy PM. Partial mechanical cardiac support: part of the solution or part of the problem? J Am Coll Cardiol 2009;54:87–8. [61] Meyns B, Klotz S, Simon A, Droogne W, Rega F, Griffith B, et al. Proof of concept: hemodynamic response to long-term partial ventricular support with the synergy pocket micro-pump. J Am Coll Cardiol 2009;54: 79–86.
Contents lists available at ScienceDirect
Medical Engineering & Physics journal homepage: www.elsevier.com/locate/medengphy
A review of clinical ventricular assist devices Daniel Timms a,b,c,∗ a
ICET Laboratory, Critical Care Research Group, The Prince Charles Hospital and University of Queensland, Brisbane, Australia Applied Medical Engineering, The Helmholtz Institute, Aachen, Germany c Dept. of Cardiovascular Engineering, Inst. for Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany b
a r t i c l e
i n f o
Article history: Received 5 June 2010 Received in revised form 18 April 2011 Accepted 23 April 2011 Keywords: Artificial organs Ventricular assist device Rotary blood pump
a b s t r a c t Given the limited availability of donor hearts, ventricular assist device (VAD) therapy is fast becoming an accepted alternative treatment strategy to treat end-stage heart failure. The field of mechanical ventricular assistance is littered with novel and unique ideas either based on volume displacement or rotary pump technology, which aim to sufficiently restore cardiac output. However, only a select few have made the transition to the clinical arena. Clinical implants were initially dominated by the FDA approved volume displacement Thoratec HeartMate I, IVAD, and PVAD, whilst Berlin Heart’s EXCOR, and Abiomed’s BVS5000 and AB5000 offered suitable alternatives. However, limitations associated with an inherently large size and reduced lifetime of these devices stimulated the development and subsequent implantation of rotary blood pump (RBP) technology. Almost all of the reviewed RBPs are clinically available in Europe, whilst many are still undergoing clinical trial in the USA. Thoratec’s HeartMate II is currently the only rotary device approved by the FDA, and has supported the highest number of patients to date. This pump is joined by MicroMed Cardiovascular’s Heart Assist 5 Adult VAD, Jarvik Heart’s Jarvik 2000 FlowMaker and Berlin Heart’s InCOR as the axial flow devices under investigation in the USA. More recently developed radial flow devices such as WorldHeart’s Levacor, Terumo’s DuraHeart, and HeartWare’s HVAD are increasing in their clinical trial patient numbers. Finally CircuLite’s Synergy and Abiomed’s Impella are two mixed flow type devices designed to offer partial cardiac support to less sick patients. This review provides a brief overview of the volume displacement and rotary devices which are either clinically available, or undergoing the advanced stages of human clinical trials. © 2011 Published by Elsevier Ltd on behalf of IPEM.
Contents 1. 2.
3.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042 Volume displacement pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042 2.1. Thoratec “HeartMate I” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042 2.2. Thoratec “IVAD/PVAD” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 2.3. Berlin Heart “EXCOR” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 2.4. Abiomed “AB5000 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 Rotary pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 3.1. Axial flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043 3.1.1. Thoratec “HeartMate II” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.1.2. Jarvik Heart “Jarvik 2000 FlowMaker” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.1.3. MicroMed Cardiovascular “Heart Assist 5 Adult VAD” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.1.4. Berlin Heart “InCOR” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044 3.2. Radial flow (centrifugal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045 3.2.1. WorldHeart “Levacor” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045 3.2.2. Terumo “DuraHeart” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045
∗ Corresponding author at: ICET Laboratory, Critical Care Research Group, The Prince Charles Hospital and University of Queensland, Brisbane 4032, Australia. Tel.: +61 7 3139 4630; fax: +61 7 3856 7330; mobile: +61 438567330. E-mail address: [email protected] 1350-4533/$ – see front matter © 2011 Published by Elsevier Ltd on behalf of IPEM. doi:10.1016/j.medengphy.2011.04.010
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3.2.3. HeartWare “HVAD” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045 Mixed flow (diagonal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 3.3.1. CircuLite synergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 Conflict of interest statement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046 3.3.
4.
1. Introduction Ventricular assist devices are employed clinically to help ease the rising demand for heart donors. These devices may be used to support a failing left and/or right ventricle, whilst being implemented as abridge to decision (BTD), bridge to myocardial recovery (BTR), bridge to heart transplantation (BTT), or indeed as a longer term destination therapy (DT) for patients in need of circulatory support. History has witnessed the development of many types of circulatory assist devices. Efforts were initially focused on devices that reproduce the pulsatile outflow delivered by the native heart [1,2]. Despite the improved one-year survival observed when treated with these devices over optimal medical therapy [3], these types were inherently flawed with reliability and durability problems, by virtue of their mode of operation. These issues led to a push to develop continuous flow devices based on a rotating impeller [4–6], which has resulted in improved outcomes for patients treated with these devices [7]. Mechanical circulatory assist devices are generally classified according to their characteristic outflow (pulsatile/volume displacement or continuous) as described in Table 1, with details relating to their operational characteristics categorising them further into first, second or third generation designs [8]. Another additional classification is emerging which categorises the devices as either providing partial or full circulatory support for short or long-term durations. The distinction indicates the target patient population, with partial support devices, often implanted via minimally invasive techniques, intended for use in less sick patients. This review provides an overview of the various types of mechanical ventricular assist devices which enable patient mobility for greater than 30 days, and are either clinically available or undergoing clinical trials to gain food and drug administration (FDA) approval. 2. Volume displacement pumps Although pumps that deliver a pulse to the circulatory system produce a similar physiologic outflow to that of the human heart, they are generally volume displacement type devices that incorporate pneumatically or electrically actuated sacs, diaphragms or pusher plates. These pumps, classified as ‘first generation’, have an inherently large tissue and blood contacting surface and have multiple moving mechanical parts including prosthetic valves. Despite advancements in affiliated technologies, these features limit the effectiveness of first generation devices as they are both difficult to fit into many patients and are prone to mechanical failure due to wear inside two or three years [9]. Furthermore, they present a high risk of infection, thrombus formation and blood trauma, which also contribute to poor patient outcomes [10]. Despite these limitations, pulsatile pumps were aggressively developed in the last century and as a result, many of these devices became clinically available to provide full mechanical circulatory support. These more commonly known and commercially available pumps are produced by companies such as Thoratec, Berlin Heart and Abiomed.
Fig. 1. HeartMate I XVE.
2.1. Thoratec “HeartMate I” The HeartMate I LVAS series evolved from the discontinued implantable pneumatic (IP) model to the vented electric VE and finally the XVE (Fig. 1) [11,12]. Both devices are medium to long term first generation volume displacement pumps. They rely on the actuation of a pusher plate that interfaces with a flexible plastic diaphragm to induce pulsatile blood flow from the left ventricular apex to the ascending aorta [13]. However, as the name suggests, the HeartMate IP was pneumatically powered, whilst the XVE utilises an electric power source to shift the pusher plate. It is for this reason that the XVE replaced its predecessor as the model of choice, since the electric supply reduces the size of the skin penetrating driveline to just ∅ 12 mm, whilst eliminating the requirement for an external compressed air source. With a size of ∅ 110 × 40 mm and weight of 1190 g, the device exhibits a somewhat restricted ability for intra-corporeal implantation into patients with a body surface area (BSA) smaller than 1.5 m2 . However, full support of up to 10 l/min is achievable at a maximum beat rate of 120 BPM. The sintered titanium blood contacting surfaces reduce the requirement for anticoagulation therapy by promoting the formation of a pseudo neo-intima lining [14]. The HeartMate XVE was involved in a randomised study (REMATCH) which demonstrated that patients exhibited an 81% improvement in two year survival with this device as opposed to Table 1 Types of clinical ventricular assist devices. Volume displacement
Rotary – Axial Flow
Rotary – Radial Flow
Rotary – Mixed Flow
Thoratec ‘HeartMate I XVE/IP’ Thoratec ‘IVAD/PVAD’ Abiomed ‘BVS5000/AB5000’ Thoratec ‘HeartMate II’ Jarvik Heart ‘Jarvik 2000 FlowMaker’ MicroMed ‘Heart Assist 5 Adult VAD’ Berlin Heart ‘InCOR’ WorldHeart ‘Levacor’ Terumo ‘DuraHeart’ HeartWare ‘HVAD’ Abiomed ‘Impella’ CircuLite ‘Synergy’
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The Berlin Heart EXCOR attained CE mark prior to 2000, and has been available for paediatric use since 2008 due to an FDA approved unconditional investigational device exemption (IDE). More than 2000 devices have been implanted worldwide to date. 2.4. Abiomed “AB5000
Fig. 2. IVAD. (Courtesy of Thoratec Corp.)
optimal medical therapy [3]. This reported success, coupled with FDA approval for DT in 2003, led to HeartMate I support in more than 4500 patients in 186 centres worldwide. 2.2. Thoratec “IVAD/PVAD” The Thoratec PVAD and IVAD are pneumatically operated first generation devices designed for short to medium term left/right or biventricular support [15]. The PVAD is a paracorporeal device that was FDA approved for BTTin 1995 and BTR postcardiotomy support in 1998, whilst the implantable IVAD (Fig. 2) was approved in 2004. Both devices maintain the same blood flow path, valves and polyurethane blood pump sac, which can deliver up to 6.5 l/min (PVAD) and 7.2 l/min (IVAD) when actuated at the maximum rate of 100 BPM. The polyurethane surface requires the chronic administration of anticoagulation therapy such as warfarin to maintain an international standard ratio (INR) of 2.0–3.0 at all times [16]. The major difference between the models, other than the semirigid polyurethane (PVAD) and titanium (IVAD) housing, is the slightly smaller size and weight (125 mm × 80 mm × 50 mm and 339 g) of the IVAD compared to the PVAD (125 mm × 80 mm × 60 mm and 417 g). This ultimately allows implantation in patients ranging from 40 to ≥100 kg or with a BSA > 1.3 m2 . Only the IVAD pump is implanted in a pre-peritoneal position with a small (∅ 9 mm) percutaneous pneumatic drive line connected to a more complex external control unit. Despite the implantability, only about 560 patients have been supported by the IVAD, compared to more than 4400 patients with the PVAD. The paracorporeal connection of the PVAD may make pump exchanges easier in the face of device malfunction or adverse events, which may explain the differences in these numbers. Furthermore, the earlier FDA approval of the PVAD provided a longer duration of clinical availability. 2.3. Berlin Heart “EXCOR” The Berlin Heart EXCOR device is a first generation, pneumatically actuated, paracorporeal VAD capable of left, right or biventricular support in adult or paediatric patients [17]. The device has a range of scale versions, with adult pumps available in 50, 60 and 80 ml sizes, whilst paediatric pumps have volumes of 10, 20 and 35 ml [18]. A maximum of 10 l/min can be delivered from the largest pump at a maximum beat rate of 150 BPM. The pump chambers are transparent polyurethane and all blood contacting surfaces are coated with heparin. However, a coagulation regime of warfarin, aspirin and dipyridamole is still recommended to maintain a relatively high INR between 3 and 3.5 [19].
The Abiomed AB5000 is a paracorporeal, pneumatically driven, first generation, volume-displacement pump, specifically designed for patient ambulation and longer support duration than the BVS5000. It too relies on a compressed air source to actuate a flexible polyurethane diaphragm contained in a relatively light (230 g) transparent pump chamber. It can be also be connected in a uni- or bi-ventricular fashion to treat cardiogenic or postcardiotomy shock, and can act alone or as a replacement for an Abiomed BVS5000 without requiring additional surgery. Despite approval by the FDA in 2003 for BTR, only a small number of the AB5000 pumps have been implanted to date [21,22]. 3. Rotary pumps Despite initial scepticism within the medical community, continuous flow type devices are now accepted for use in mechanical circulatory assist therapy. Although concerns regarding the long term physiological effects of ‘non-pulsatile’ support remain, the distinct advantages of small size and superior mechanical longevity have accelerated acceptance of this form of therapy over traditional pulsatile devices. In cases of remaining cardiac contractility, some degree of pulsatility remains under normal operation, as the inlet pressure to the pump is cyclical according to the cardiac cycle phase of the native left ventricle to which it is often connected. Furthermore, the level of electrical power needed to operate these devices results in a relatively small driveline, which acts to reduce the incidence of device related infection. The number of patients ultimately supported with this form of technology is increasing, and studies have appeared that demonstrate improvements in patient outcomes when compared to earlier volume displacement devices [7]. Devices in this category produce their characteristic partial or full support continuous flow via a rotating impeller housed within a small pump chamber, without the need for directional valves. This impeller can be termed axial, radial (centrifugal), or mixed flow, and refers to the direction to which the blood enters and leaves the impeller. These rotary pumps formed the beginning of the second generation of devices, characterised by a contact shaft/roller bearing/seal or blood immersed (pivot) bearing impeller support mechanism. Whilst these devices have proven capable of supporting the circulation, the remaining mechanical contact is thought to impose a serious contraindication for long term use in excess of five years [23]. Several techniques have since been proposed to solve this concern, which gave rise to the latest, third generation of devices. These systems effectively eliminate mechanical contact and thus wear by completely suspending the rotating impeller using magnetic or hydrodynamic forces, potentially increasing device lifetime beyond ten years [24]. Many cardiovascular device manufacturers have understood the advantages of the rotary/continuous flow approach and as such have invested considerable resources into developing suitable devices. 3.1. Axial flow Axial flow rotary blood pumps are small and contain an impeller that can spin at speeds between 6000 and 15,000 rpm to deliver blood flow to the circulatory system. Owing to their small size, most axial flow devices are limited to second generation pumps, however, third generation technology has also been utilised in one
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Since the initiation of clinical trials in July 2000, and FDA approval for BTT in 2008 and DT in 2010, more than 5000 patients worldwide have been implanted with the device. The HeartMate II was also instrumental in a recent study which advocated superior results in patients receiving non-pulsatile type mechanical circulatory support [7].
Fig. 3. Heart Assist 5. (Courtesy of Jarvik Heart Inc.)
instance [25]. The required impeller peripheral velocity is higher than other rotary type devices, which may contribute to relatively higher shear stress development and thus levels of haemolysis and platelet activation. Furthermore, the need for stationary guide vanes and a contact impeller suspension may promote thrombus formation in areas of recirculation or stagnation. Finally, due to the combination of a high rotational speed and contact pivot bearing support mechanism, the service life of axial flow pumps is predicted at below five years. However, there have been reported instances of longer support [26]. All axial flow devices are capable of providing full circulatory support. Manufacturers Thoratec Corporation, Jarvik Heart, MicroMed Cardiovascular, and Berlin Heart are leading the field, with all possessing CE mark approval. At this stage, only the HeartMate II is approved by the FDA, however, other devices are nearing their IDE trial endpoints and submission for BTT status should follow soon. Helped by its regulatory status, the HeartMate II device has been implanted in up to 10 times more patients than any other rotary device.
3.1.1. Thoratec “HeartMate II” The HeartMate II (Fig. 3) is an implantable, second generation, axial flow pump that provides full circulatory support (up to 10 l/min) to left heart failure patients. The small device (∅ 40 × 60 mm), approximately the size of a D-Cell battery, weighs 375 g and incorporates an electromagnetic DC brushless motor to provide rotation to the dual cup-socket ruby bearing supported impeller which has demonstrated a five year service life. Operating speeds between 6000 and 15,000 rpm are possible, with suitable haemodynamic pressures and flows typically produced at 9000 rpm [27,28]. Redesigns of the pivot bearing area have ensured that it is well washed, in an attempt to limit thrombus formation. However, somewhat paradoxically, anticoagulation therapy has been reduced in these patients to maintain a low INR of just 1.5–2.0 [29]. It has been suggested that acquired von Willebrand syndrome caused by shear stresses in the device may play a role in this observation [30].
3.1.2. Jarvik Heart “Jarvik 2000 FlowMaker” The Jarvik 2000 FlowMaker is a long term implantable, full support, second generation, axial flow pump that resides in the ventricular cavity and circulates blood to the ascending or descending aorta [31]. Whilst predominately used for left ventricular assistance, owing to the small size and weight (∅ 25 × 55 mm and 85 g), a few clinical cases have been reported of right [32] or biventricular assistance [33]. The impeller, supported at each end by tiny blood-immersed ceramic bearings, constitutes the only moving part of the device, which can deliver flow rates of 3–7 l/min at 8000–12,000 rpm [28]. These bearings require the patient to chronically maintain a warfarin induced INR of 2.5–3.5 [34]. No implantable components have failed throughout the clinical experience of more than 357 patients since the first implant in April 2000. Despite the mechanical contact impeller support, one patient was supported for more than seven years [35]. A low risk of infection is also apparent in DT patients, which is due in part to the delivery of power via a small post auricular pedestal [36]. However, a more conventional exit from the sub costal margin is often selected in BTT patients. 3.1.3. MicroMed Cardiovascular “Heart Assist 5 Adult VAD” The MicroMed Heart Assist 5 LVAD is a miniaturised, implantable, second generation, axial flow pump capable of long term circulatory support for left heart failure [37]. The electromagnetically driven pump weighs 95 g, and is ∅ 25 × 86 mm in dimension. The pump connects the left ventricle (LV) apex to the ascending aorta, and pumps 5–6 l/min at 10,000 rpm, with flows of over 10 l/min possible when operated at a maximum speed of 12,500 rpm. These flow rates are measured directly with an ultrasonic flow probe placed around the outflow graft, a feature unique to this device. The impeller is supported with front and back mechanical pivot bearings, incorporated in the flow straightening inducer and stationary outlet diffuser. The durability of the contact bearing has proven to exceed two years. Cameda® biocompatible coating is applied to the blood contacting surfaces in an attempt to limit the incidence of thrombus formation, which plagued earlier iterations of this device. Subsequent iterations have addressed this concern, with the patient required to maintain an INR of 2.5–3.5 via coumarin [28,38]. Clinical trials were initiated in 1998, with more than 440 implants taking place since, significantly less than the more recently developed HeartMate II device. CE mark approval for the adult VAD was attained in 2010, whilst a humanitarian device exemption (HDE) was awarded by the FDA in 2005 for a paediatric version of the device. 3.1.4. Berlin Heart “InCOR” The InCOR left ventricular assist device (Fig. 4) is a long term, implantable, third generation, axial flow pump that circulates blood from the LV apex to the ascending aorta in left heart failure patients [39]. Complete rotor suspension is achieved with active axial electromagnetic bearings positioned at each end of the rotor, which passively constrain radial movement and tilting of the rotor. At a size of ∅ 30 × 120 mm, it is the largest of the axial flow devices, whilst its magnetic system contributes to its device weight of 200 g [40].
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Fig. 4. Incor. (Courtesy of Berlin Heart GmbH.)
The device includes a stationary inlet inducer and outlet diffuser which assist the rotor to produce 5 l/min at 8000 rpm, with a maximum flow rate of 7 l/min achievable with speeds of 10,000 rpm [28]. A unique control algorithm is implemented to determine pump performance characteristics. Using the magnetic bearing configuration, the rotor position is measured in the magnetic field, which is then used to control the pump speed [41]. All blood-contacting surfaces are heparin coated with Carmeda® to improve biocompatibility. An anticoagulation strategy using clopidogrel or dipyridamole has been reported to maintain an INR of 2.5–3.0 [42]. Thromboembolic related neurologic complications were observed in early clinical applications. However, a modified inlet cannula, which protruded a further 10 mm into the left ventricular cavity, significantly reduced these adverse events [42]. The first human clinical trial occurred in June, 2002 and following CE mark approval in 2003, more than 500 implants worldwide have since taken place. The device is, however, unavailable in the USA at this time. 3.2. Radial flow (centrifugal) Whilst slightly larger in diameter than axial flow devices, radial flow (centrifugal) pumps are suitable for long term cardiac assistance due to their lower corresponding rotational speed, higher hydraulic efficiency (for blood pump applications), elimination of stationary vanes and a more anatomically suitable flatter shaped profile. Furthermore, due to their rotor geometry and increased surface area, these pumps can take advantage of the third generation bearing technology to completely suspend the impeller using hydrodynamic or magnetic bearing forces. This effectively eliminates component wear, potentially increasing device lifetime to beyond ten years. All radial flow devices provide full circulatory support, with manufacturers WorldHeart, Terumo, and HeartWare developing devices that have either received a CE mark in Europe or are undergoing clinical trials for FDA approval in the USA. Implant numbers of this latest generation technology do not currently match previous generation devices; however, the HeartWare HVAD is rapidly increasing in numbers, with implantations already surpassing all previous rotary devices bar the HeartMate II, in just a few years. 3.2.1. WorldHeart “Levacor” The Levacor LVAD, formerly ‘Heartquest’, is a long term, implantable, third generation, radial flow pump that integrates a hybrid active and passive magnetic bearing to completely suspend a centrifugal impeller [43]. Designed for left ventricular assistance in BTT and DT applications, the device has also been used for BTR [44]. Although heavier (440 g) and larger in size (∅ 75 × 35 mm) than all axial flow rotary pumps [45], complete suspension eliminates device lifetime limiting wear. This device can produce flows ranging
Fig. 5. DuraHeart. (Courtesy of Terumo Heart Inc.)
from 0 to 10 l/min, with 5 l/min achievable with a rotational speed of around 2000 rpm. The lower flow rate is advantageous when weaning the patient in BTR applications, however, may increase the potential for thrombus formation in the pump. The polished titanium blood contacting surfaces attempts to limit thrombotic events in cooperation with an anticoagulation strategy targeting a relatively high chronic INR of 3.0–3.5 with aspirin/clopidogrel/dipyridamole. The Levacor is currently an investigational device in the USA, limited by the FDA for bridge to transplant applications. Clinical evaluation began in 2006 [46], with only ∼17 patients supported by the device to date. Regulatory trials are underway in the USA (BTT) and Europe. 3.2.2. Terumo “DuraHeart” The DuraHeart LVAD (Fig. 5) is an implantable, third generation, radial flow pump that incorporates an axial magnetic bearing (MB) to provide long term left ventricular assistance with a contact-free impeller suspension system [47]. The device is the largest and heaviest of the rotary pumps, with a size of ∅ 72 × 45 mm and weight of 540 g [48]. However, the relatively large (250 m) clearance gaps, characteristic of MBs, have the potential to reduce blood trauma. An external brushless DC motor achieves impeller rotational speeds from 1200 to 2600 rpm via a direct coupled magnetic drive to provide full circulatory support between 2 and 10 l/min. A backup spiral groove hydrodynamic bearing is incorporated into the titanium housing between the motor and the rotor to provide continued non-contact suspension should the primary magnetic bearing system fail. The blood contacting titanium surfaces benefit from a covalently bonded heparin coating to prevent thrombosis formation in the pump interior. This is further enhanced by a chronic anticoagulation regime of warfarin that achieves an INR of 2.5–3.0. Clinical implants of the DuraHeart started in January 2004, with CE approval attained in 2007. The large device size and resulting inflow cannula placement difficulties, however, have restricted device implants to just over 118 patients to date. 3.2.3. HeartWare “HVAD” The HeartWare HVAD (Fig. 6) is a third generation, radial flow pump, implanted in the pericardial cavity. The HVAD draws blood from an integrated inflow cannula inserted directly into the ventricular cavity. Initially designed for left ventricular assistance, the device has also been modified for bi-ventricular assistance [49,50], however, no studies have methodically evaluated the appropriateness of this approach. The single rotating impeller is completely suspended via a combination of passive magnetic and hydrodynamic forces created via a tapered thrust axial bearing [23,51]. The device is the smallest
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Fig. 6. HVAD. (Courtesy of Heartware International Inc.)
(∅ 50 mm) and lightest (145 g) of the radial flow pumps. The dual flat axial flux motor arrangement rotates the impeller at a typical speed of 2400 rpm, whilst speeds between 1800 and 4000 rpm are possible, delivering up to 10 l/min [51]. The dual motor provides a level of redundancy. The lower speed limit ensures the continued generation of sufficient hydrodynamic lift to maintain stable impeller levitation. A ceramic–titanium blood contacting surface is used to mitigate thrombus formation inside the pump. Achieving a chronic INR of 2.5–3.0 with warfarin also helps to maintain thrombus free operation [52]. Clinical trials of the HVAD device began in 2008, with more than 700 patients now implanted worldwide. CE mark was attained in 2009, and an IDE BTT trial was completed in 2010 for submission to the FDA. 3.3. Mixed flow (diagonal) As the name suggests, mixed flow devices are a mixture between axial and centrifugal flow pumps. Fluid enters axially whereby it is pumped diagonally, collected, and distributed radially. The impeller is relatively difficult to completely suspend, thus mixed flow devices are generally based on second generation support techniques. The only mixed flow device that is undergoing clinical trial, is manufactured by CircuLite. 3.3.1. CircuLite synergy The Synergy Pocket Circulatory Assist Device (Fig. 7) is a new concept ventricular assist device that is intended to provide partial left ventricular circulatory support for patients classified with NYHA class III heart failure/INTERMACS 4+ [55].
Fig. 7. Synergy. (Courtesy of Circulite Inc.)
The miniature device is the smallest and lightest medium to long term, rotary pump in the clinical arena, measuring just ∅ 12 × 50 mm in its initial prototype form and weighing 25 g [56]. These features allow the device to be implanted into the pacemaker pocket via a less invasive left thoracotomy [57,58]. The unique anatomical connection sees the inflow cannulating the left atrium (LA), with the outflow directed to a peripheral artery (e.g. subclavian artery) [59]. This method of cannulation reduces the typical left ventricular apical trauma associated with conventional LVAD insertion whilst also reducing the workload of the heart, thus providing a suitable environment for BTR applications. A pivot bearing supported mixed flow impeller, contained in the titanium housing, is rotated at 20,000–28,000 rpm to provide 2–3.5 l/min of partial support. This lower flow however is of concern for pump thrombus formation [60], and may be a factor contributing to the high rate of pump exchanges required in an initial pilot study of the device, despite a suitable anticoagulation strategy that maintained an INR of 2.5–3.0 [61]. A clinical CE mark trial of the device began in 2007 in Europe and has so far been implanted in at least 27 patients. 4. Conclusion The improved clinical results of end stage heart failure patients treated with mechanical circulatory support therapy over medically managed patients has driven the acceptance of ventricular assist device technology by the medical community. Despite the initial clinical dominance of volume displacement type devices, their inherent limitations have driven VAD developers toward smaller, more reliable, rotary pump technology. This has resulted in the clinical investigation and/or availability of numerous axial, centrifugal or diagonal type devices, which have been shown to produce superior clinical results when compared to their volume displacement predecessors. Continued clinical experience with these devices will no doubt improve patient outcomes, propelling more devices into the clinical arena, which will expand the numbers of patients treated with this life saving technology. Conflict of interest statement The author has no conflict of interest that would influence the content of this manuscript. References [1] Guy T. Evolution and current status of the total artificial heart: the search continues. ASAIO J 1998;44:28–33. [2] Copeland J, Smith R, Arabia F, Nolan P, Mehta V, McCarthy M, et al. Comparison of the cardiowest total artificial heart, the novacor left ventricular assist system and the thoratec ventricular assist system in bridge to transplantation. Ann Thorac Surg 2001;71:S92–7. [3] Rose E, Gelijns A, Moskowitz A, Heitjan D, Stevenson L, Dembitsky W, et al. Long-term use of a left ventricular assist device for end stage heart failure. N Engl J Med 2001;345:1435–43. [4] Maslen EH, Bearnson GB, Allaire PE, Flack RD, Baloh M, Hilton E, et al. Feedback control applications in artificial hearts. IEEE Control Syst Mag 1998;18:26–34. [5] Kung RTV, Hart RM. Design considerations for bearingless rotary pumps. Artif Organs 1997;21:645–50. [6] Meyns B. Ventricular support with miniature rotary blood pumps. Leuven University Press; 1997. [7] Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 2009;361:2241–51. [8] Yamane T. The present and future state of nonpulsatile artificial heart technology. J Artif Organs 2002;5:149–55. [9] Maslen EH, Bearnson GB, Allaire PE, Flack RD, Baloh M, Hilton E, et al. Artificial hearts. In: Proceedings of the 1997 IEEE international conference on control applications. 1997. p. 204–9. [10] Frazier O, Rose E, Macmanus Q, Burton N, Lefrak E, Poirier V, et al. Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device. Ann Thorac Surg 1992;53:1080–90.
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