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The evolution of cardiac assist device technology
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EDITORIAL COMMENTARY
The evolution of cardiac assist device technology See companion article on page 13 and 21.
Long-term implantable mechanical circulatory assistance as a clinically viable entity started with the approval of the HeartMate XVE as bridge to transplantation. Results of the REMATCH trial led to the device to be approved for destination therapy.1 The only other implantable pulsatile devices approved in the United States are the WorldHeart Novacor left ventricular assist device (LVAD) and the SynCardia total artificial heart (TAH). The Abiomed Abiocor TAH is available under a humanitarian device exemption. These first-generation pumps were designed to mimic nature and produce pulsatile blood flow. There has been much debate on the need for pulsatility. Temporary non-pulsatile flow is used routinely during cardiopulmonary bypass to support patients undergoing cardiac surgery. Animal data suggest that non-pulsatile flow might not deliver as much perfusion to the distal vasculature and might lead to a weakening of the muscle in the walls of major arteries.2,3 However, achieving pulsatile flow leads to several engineering challenges. A diaphragm or sac is required to eject the blood. Flexing of this biomaterial interface can lead to failure after millions of cycles. Air is often required to compensate for the volume displacement. Some devices have used large compliance chambers or have allowed venting to the outside air. Mechanical energy is derived from a pusher plate–type motor, which has decreased device durability. For instance, despite excellent in vitro testing results, the bearings on the HeartMate XVE wear out after 14 to 18 months and require replacement. The most mechanically durable device has proven to be the Novacor LVAD, which works by having two magnetic plates squeeze a bladder placed between them. Pulsatility also requires valves to be placed to maintain the direction of proper blood flow. Although these valves work well when used for replacement in the native heart, the additional stresses imparted by a mechanical motor cause premature failure, which then leads to VAD valve regurgitation and subsequent heart failure. These devices are bulky as they Reprint requests: Valluvan Jeevanandam, MD, Department of Surgery, University of Chicago, AMB-E-511, 5841 South Maryland Avenue, Chicago, IL 60637. Telephone: 773-702-2500. Fax: 773-834-9114. E-mail address: [email protected]
have to at least be the size of the bladder displacement (usually 60 to 80 cc) and hence have to be placed in the preor intraperitoneal space. These technical limitations mandated by pulsatile devices have led to decreased reliability and durability and a high incidence of infections. Furthermore, the major surgery required for implantation increases the rate of bleeding, peri-operative complications, length of hospital stay, and need for rehabilitation.2 The next generation of devices is continuous-flow (CF) pumps. The HeartMate II device is approved as a bridge to transplant and will soon be approved for destination therapy.3,4 The HeartWare HVAD, Jarvik 2000, Terumo DuraHeart, and Ventracor VentrAssist devices are in clinical trials and hopefully will be approved in the near future. Compared with the previous pulsatile devices, CF pumps cannot completely decompress the left ventricle as the native heart must have some residual volume to prevent suction events. Therefore, the native heart continues to eject and this provides a moderate amount of pulsatility. In many patients, this ejection occurs through the LVAD and the aortic valve can remain closed. This low level of pulsatility is apparently enough to increase end-organ perfusion and allow these patients (specifically their kidneys) to recover from chronic congestive heart failure (CHF). Because the CF devices do not have to displace blood like the pulsatile devices, they are much smaller. Also, as they contain only one moving part, the rotor, they tend to be much more reliable. The HeartMate II device is an axial-flow pump, so the direction of blood flow is parallel to the rotor. Devices such as the HVAD, DuraHeart, and VentrAssist are centrifugal and the inflow and outflow of blood are in perpendicular directions. Some devices are magnetically levitated and are so durable that they could potentially outlive the lifespan of the patient. Because they are much smaller and do not have the constant motion caused by blood displacement, the infection rates are dramatically decreased.5 Furthermore, the drive-lines are also much smaller because they only contain wires and do not need a conduit for venting air. The improved results with the CF devices, specifically with better durability and less need for device exchange, has led to an exponential increase in the
1053-2498/10/$ -see front matter © 2010 International Society for Heart and Lung Transplantation. All rights reserved. doi:10.1016/j.healun.2009.07.024
12
The Journal of Heart and Lung Transplantation, Vol 29, No 1, January 2010
number of patients being supported with mechanical circulatory assistance. Two articles in this issue of the journal describe a novel device for applying CF to a TAH.6,7 If the device is successful and can be used clinically, it may be an improvement over the Abiocor pump in terms of reliability and smaller size, and over the SynCardia device because it will be implantable without requiring an external pneumatic driver. The proposed Cleveland Clinic pump is elegant in its simplicity. It has one central rotor in between the right- and left-side chambers. The rotor can float within the central position, so it is self-regulating. If the left-side chamber is relatively empty, the rotor moves toward the left, allowing for a larger right-side chamber and hence increasing rightside blood flow. This will in turn increase volume delivery to the left chamber, which will allow the rotor to compensate by moving to the right and decreasing the flow of that chamber. In vivo testing has demonstrated the ability of the pump to work over a wide range of pulmonary and systemic resistances. The rotor can also be driven at variable speeds to allow for some modest pulsatility. The only real control is the speed of the pump, which should allow for a more reliable device. The device is also small, which should allow placement in almost any adult size pericardial space. Of course, the data available currently are early and involve acute experiments in open chest animals. It will be of great interest to see how the animal implants progress once the phase requiring activity and survival is entered. The trend in circulatory assistance is toward CF devices. They offer many advantages over the pulsatile devices in terms of size, reliability, durability, and infection. However, long-term results will need to be followed closely, specifically with regard to the persistently high rates of bleeding well after the peri-operative period and the incidence of cerebrovascular accident (CVA) despite appropriate anti-coagulation. Perhaps the lack of significant pulsatility causes a decrease in vascular wall
strength and integrity. CF LVADs have been approved and their use is increasing rapidly. Hopefully, devices like the Cleveland Clinic TAH can transition CF principles to a TAH and allow the technology to be used in patients requiring biventricular support.
Disclosure statement The author is a member of the clinical events committee for the REMATCH and HeartMate II trials, serves as chairman of the DSMB for the DuraHeart trial, and is site principal investigator for the HVAD trial. Valluvan Jeevanandam, MD From the Department of Surgery, University of Chicago Chicago, Illinois
References 1. Lietz K, Long JW, Kfoury AG, et al. Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era. Circulation 2007;116:497-505. 2. Yada I, Mitamura Y. Pulsatile flow versus nonpulsatile flow. J Artif Organs 1999;2:1-2. 3. Potapov EV, Loebe M, Nasseri BA, et al. Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device. Circulation 2000;102(suppl):III-183-7. 4. Boyle A. Current status of cardiac transplantation and mechanical circulatory support. Curr Heart Fail Rep 2009;6:28-33. 5. Miller LW, Pagani FD, Russell SD, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007; 357:885-96. 6. Fukamachi K, Horvath DJ, Massiello AL, et al. An innovative, sensorless, pulsatile, continuous-flow total artificial heart: device design and initial in vitro study. J Heart Lung Transplant 2010;29:13-20. 7. Fumoto H, Horvath DJ, Rao S, et al. In vivo acute performance of the Cleveland Clinic self-regulating, continuous-flow total artificial heart. J Heart Lung Transplant 2010;29:21-26.
EDITORIAL COMMENTARY
The evolution of cardiac assist device technology See companion article on page 13 and 21.
Long-term implantable mechanical circulatory assistance as a clinically viable entity started with the approval of the HeartMate XVE as bridge to transplantation. Results of the REMATCH trial led to the device to be approved for destination therapy.1 The only other implantable pulsatile devices approved in the United States are the WorldHeart Novacor left ventricular assist device (LVAD) and the SynCardia total artificial heart (TAH). The Abiomed Abiocor TAH is available under a humanitarian device exemption. These first-generation pumps were designed to mimic nature and produce pulsatile blood flow. There has been much debate on the need for pulsatility. Temporary non-pulsatile flow is used routinely during cardiopulmonary bypass to support patients undergoing cardiac surgery. Animal data suggest that non-pulsatile flow might not deliver as much perfusion to the distal vasculature and might lead to a weakening of the muscle in the walls of major arteries.2,3 However, achieving pulsatile flow leads to several engineering challenges. A diaphragm or sac is required to eject the blood. Flexing of this biomaterial interface can lead to failure after millions of cycles. Air is often required to compensate for the volume displacement. Some devices have used large compliance chambers or have allowed venting to the outside air. Mechanical energy is derived from a pusher plate–type motor, which has decreased device durability. For instance, despite excellent in vitro testing results, the bearings on the HeartMate XVE wear out after 14 to 18 months and require replacement. The most mechanically durable device has proven to be the Novacor LVAD, which works by having two magnetic plates squeeze a bladder placed between them. Pulsatility also requires valves to be placed to maintain the direction of proper blood flow. Although these valves work well when used for replacement in the native heart, the additional stresses imparted by a mechanical motor cause premature failure, which then leads to VAD valve regurgitation and subsequent heart failure. These devices are bulky as they Reprint requests: Valluvan Jeevanandam, MD, Department of Surgery, University of Chicago, AMB-E-511, 5841 South Maryland Avenue, Chicago, IL 60637. Telephone: 773-702-2500. Fax: 773-834-9114. E-mail address: [email protected]
have to at least be the size of the bladder displacement (usually 60 to 80 cc) and hence have to be placed in the preor intraperitoneal space. These technical limitations mandated by pulsatile devices have led to decreased reliability and durability and a high incidence of infections. Furthermore, the major surgery required for implantation increases the rate of bleeding, peri-operative complications, length of hospital stay, and need for rehabilitation.2 The next generation of devices is continuous-flow (CF) pumps. The HeartMate II device is approved as a bridge to transplant and will soon be approved for destination therapy.3,4 The HeartWare HVAD, Jarvik 2000, Terumo DuraHeart, and Ventracor VentrAssist devices are in clinical trials and hopefully will be approved in the near future. Compared with the previous pulsatile devices, CF pumps cannot completely decompress the left ventricle as the native heart must have some residual volume to prevent suction events. Therefore, the native heart continues to eject and this provides a moderate amount of pulsatility. In many patients, this ejection occurs through the LVAD and the aortic valve can remain closed. This low level of pulsatility is apparently enough to increase end-organ perfusion and allow these patients (specifically their kidneys) to recover from chronic congestive heart failure (CHF). Because the CF devices do not have to displace blood like the pulsatile devices, they are much smaller. Also, as they contain only one moving part, the rotor, they tend to be much more reliable. The HeartMate II device is an axial-flow pump, so the direction of blood flow is parallel to the rotor. Devices such as the HVAD, DuraHeart, and VentrAssist are centrifugal and the inflow and outflow of blood are in perpendicular directions. Some devices are magnetically levitated and are so durable that they could potentially outlive the lifespan of the patient. Because they are much smaller and do not have the constant motion caused by blood displacement, the infection rates are dramatically decreased.5 Furthermore, the drive-lines are also much smaller because they only contain wires and do not need a conduit for venting air. The improved results with the CF devices, specifically with better durability and less need for device exchange, has led to an exponential increase in the
1053-2498/10/$ -see front matter © 2010 International Society for Heart and Lung Transplantation. All rights reserved. doi:10.1016/j.healun.2009.07.024
12
The Journal of Heart and Lung Transplantation, Vol 29, No 1, January 2010
number of patients being supported with mechanical circulatory assistance. Two articles in this issue of the journal describe a novel device for applying CF to a TAH.6,7 If the device is successful and can be used clinically, it may be an improvement over the Abiocor pump in terms of reliability and smaller size, and over the SynCardia device because it will be implantable without requiring an external pneumatic driver. The proposed Cleveland Clinic pump is elegant in its simplicity. It has one central rotor in between the right- and left-side chambers. The rotor can float within the central position, so it is self-regulating. If the left-side chamber is relatively empty, the rotor moves toward the left, allowing for a larger right-side chamber and hence increasing rightside blood flow. This will in turn increase volume delivery to the left chamber, which will allow the rotor to compensate by moving to the right and decreasing the flow of that chamber. In vivo testing has demonstrated the ability of the pump to work over a wide range of pulmonary and systemic resistances. The rotor can also be driven at variable speeds to allow for some modest pulsatility. The only real control is the speed of the pump, which should allow for a more reliable device. The device is also small, which should allow placement in almost any adult size pericardial space. Of course, the data available currently are early and involve acute experiments in open chest animals. It will be of great interest to see how the animal implants progress once the phase requiring activity and survival is entered. The trend in circulatory assistance is toward CF devices. They offer many advantages over the pulsatile devices in terms of size, reliability, durability, and infection. However, long-term results will need to be followed closely, specifically with regard to the persistently high rates of bleeding well after the peri-operative period and the incidence of cerebrovascular accident (CVA) despite appropriate anti-coagulation. Perhaps the lack of significant pulsatility causes a decrease in vascular wall
strength and integrity. CF LVADs have been approved and their use is increasing rapidly. Hopefully, devices like the Cleveland Clinic TAH can transition CF principles to a TAH and allow the technology to be used in patients requiring biventricular support.
Disclosure statement The author is a member of the clinical events committee for the REMATCH and HeartMate II trials, serves as chairman of the DSMB for the DuraHeart trial, and is site principal investigator for the HVAD trial. Valluvan Jeevanandam, MD From the Department of Surgery, University of Chicago Chicago, Illinois
References 1. Lietz K, Long JW, Kfoury AG, et al. Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era. Circulation 2007;116:497-505. 2. Yada I, Mitamura Y. Pulsatile flow versus nonpulsatile flow. J Artif Organs 1999;2:1-2. 3. Potapov EV, Loebe M, Nasseri BA, et al. Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device. Circulation 2000;102(suppl):III-183-7. 4. Boyle A. Current status of cardiac transplantation and mechanical circulatory support. Curr Heart Fail Rep 2009;6:28-33. 5. Miller LW, Pagani FD, Russell SD, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007; 357:885-96. 6. Fukamachi K, Horvath DJ, Massiello AL, et al. An innovative, sensorless, pulsatile, continuous-flow total artificial heart: device design and initial in vitro study. J Heart Lung Transplant 2010;29:13-20. 7. Fumoto H, Horvath DJ, Rao S, et al. In vivo acute performance of the Cleveland Clinic self-regulating, continuous-flow total artificial heart. J Heart Lung Transplant 2010;29:21-26.