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This presentation will present information on current long-term mechanical support applications and future trial designs for investigation affecting this public health issue. At the conclusion of this lecture, the participant will be able to:
1. Identify the different mechanical support devices available and give an overview.
2. Compare and contrast optimal medical therapy and destination VAD therapy including looking at REMATCH trials and any other pertinent trials.
3. Understand the physiology and management of pulsatile flow versus axial flow devices.
Mechanical circulatory support is used to treat patients with advanced heart failure.
Heart failure causes low cardiac output, which results in inadequate blood pressure and reduced blood flow to the brain, kidneys, heart, and/or lungs. Pharmaceutical and surgical treatments, other than transplantation, are all typically exhausted before mechanical circulatory support is initiated. The extent of failure exhibited by one or both ventricles of the heart determines if univentricular or biventricular support is required. In either case, blood flow is supplemented or replaced by a mechanical circulatory support device. A mechanical pump is surgically implanted to provide pulsatile or non-pulsatile flow of blood to supplement or replace the blood flow generated by the native heart. The device works by removing blood from the inlet of the ventricle(s) and reinjecting it at the outlet of the ventricle(s) in order to increase or sustain blood pressure and blood flow to the brain, kidneys, heart, and lungs. If recovery does not occur, or is not expected, then heart transplantation becomes the next desired course of treatment. In this case, intermediate- to long-term mechanical circulatory support devices are required to sustain the patient to recovery or organ transplantation. In some instances, patients have been able to leave the hospital for continued treatment at home with the implanted device. This type of treatment is called bridge to organ transplantation. Complete recovery of the heart has been demonstrated in 5 15% of patients being supported as a bridge to organ transplantation. (1)
MECHANICAL SUPPORT DEVICES
Mechanical circulatory support pumps include pneumatic, electromagnetic and rotary pumps.
The major left ventricular assist systems (LVAS) and devices (LVAD) can be subdivided into categories that include: implantable tethered pulsatile devices, paracorporeal pulsatile devices, rotary axial flow pumps, centrifugal pumps, totally implantable pulsatile devices, and the total artificial heart (TAH). (1,2,3)
IMPLANTABLE PULSATILE DEVICES
Pulsatile paracorporeal mechanical circulatory support devices provide pulsatile support for the left or right ventricle, or both. Cannulation of the left or right atrium, along with the aorta or pulmonary artery, respectively, requires a surgical approach. The heart is emptied of blood by the assist device, so there is little ejection from the body's heart. (1,4,6) Removal of the device occurs at the time of cardiac transplant, unless the body's heart has healed during support. Anticoagulation is achieved by low doses of drugs. Some patients regain mobility while assisted by these devices. (1,6)
The HeartMate LVAD (Thoratec Corporation, Pleasanton. CA) was designed in 1975. (7)
It was originally a pneumatic vented system that required a large cumbersome console that did not allow patients much mobility outside the hospital. Since 1986, this system has proven to be effective as a long-term support device with the end goal of heart transplantation.(7,8,9,10) The system underwent years of development and in 1991 a clinical trial of an electric vented (VE) model was begun..
The Novacor (World Heart Corp., Ottawa, ON, Canada) left ventricular assist system (LVAS) was developed and first used in 1984 in a successful bridge to transplant application. (7) Initially designed as a totally implantable system for long-term support, it has evolved through a console-based controller system to a wearable controller that has been available since 1993.
PARACORPOREAL PULSATILE DEVICES
Numerous Pierce-Donachy type pumps are available, such as Thoratec, Medos, German Heart, and Toyobo Heart. The Thoratec Ventrical Assistance Device (VAD) will be presented since it is the most utilized among these type devices. Also known as displacement pumps are classified as intracorporeal or extracorporeal. (2) Sometimes the term paracorporeal is used interchangeably with the term extracorporeal . (8)
The Thoratec VAD (Thoratec Laboratories Corp., Pleasanton, CA) is another reliable and often used system for ventricular support. (7) Thoratec is a paracorporeal system that can be applied for univentricular or biventricular support unlike HeartMate and Novocor or systems. Since the actual pump chamber is outside of the body, this device can be used on patients with small body size who would not meet the size criteria to house a HeartMate or Novacor system. However, a paracorporeal system limits mobility and presents an obstacle for patients in long-term use.
The Excor LVAD (Berlin Heart AG Berlin, Germany) is a paracorporeal pneumatically driven left ventricular assist device utilizing a 25 ml chamber. This device has been successfully used in infants and children. (11).
ROTARY AXIAL FLOW PUMPS
Provides continuous blood flow in circulatory support. The axial pumps have the advantage of smaller size, less power consumption, minimal moving parts, and no valves. The most commonly used pumps will be presented. (7,8) Rotary axial pumps can be used in adults or children. (8,11)
Axial Flow Pumps
The MicroMed-DeBakey VAD (Houston, TX) was initially developed in the 1980s as a collaboration between Dr. George Noon and Dr. Michael DeBakey of Baylor College of Medicine and engineers from NASA. (7,8) MicroMed Technology, Inc., received the license for this technology in 1996 and has continued to develop this device for clinical use. (7,8) The flow is not nonpulsatile but is low pulsatile due to the recovering ventricle and change in ventricular volume) Patients with the device have ability to go home with the device while awaiting transplantation. (7)
The Jarvik 2000 (Jarvik Heart, Inc., New York, NY) is another extensively developed axial-flow pump initially developed by Dr. Jarvik. Unlike the DeBakey VAD or the HeartMate II pump, the Jarvik 2000 pump is positioned inside the ventricle with the outflow graft extended to the descending aorta. A percutaneous model that, like most other LVAD systems, has a power lead that exits the patient's skin; a fully implantable model that uses the transcutaneous energy transfer system (TETS), which is still in development. Unlike the other systems, which require a sternotomy, the Jarvik 2000 is implanted through a left thoracotomy incision. Similar to other systems, the pump provides a low pulsatile flow with a narrowing of pulse pressure at higher speeds. (7,9) Required anticoagulation is reported to be minimal with some patients taking warfarin while others showing no clot formation with only aspirin.
The HeartMate II LVAD (Thoratec Corp., Pleasanton, CA), like the two previously mentioned pumps, is an axial flow pump that had its origin in the early 1990s with a collaboration between Nimbus Company and the University of Pittsburgh. Similar to the other pumps, this is an axial-flow rotary LVAD. Anticoagulation is at present required to keep INR between 1.5 and 2.5. The pump is small (124 mL) and is inserted preperitoneally or within the abdominal musculature. Power and control are supplied by a percutaneous lead that is attached to a system driver that can be connected to a power base unit or to rechargeable batteries and worn in a manner similar to the pulsatile HeartMate LVAD. The system can be operated in manual or auto mode with the auto mode preferred for everyday use. (7,9) Currently research is underway to develop and test a totally implantable system using TETS coil to deliver power to the system. (7,9)
TOTALLY IMPLANTABLE PULSATILE DEVICES
Implantable devices have been shown to be safe and effective as bridges to cardiac transplantation and as the future of destination therapy draws near, completely implantable devices become increasingly important. Two design issues with total implantable systems involve energy transfer and volume displacement
Arrow LionHeart LVD-2000
The Arrow LionHeart LVD-2000 (Pennsylvania State University and Arrow International) is the first system designed specifically with destination support in mind. It is a completely implantable system with a transcutaneous energy transmission system (TETS) and a compliance chamber, which allows for complete implantation with no percutaneous lines or connections. Recharging of the battery is accomplished through a transcutaneous system with a wand overlying the skin over the recharging coil. The patient may be completely disconnected from the external power supply for a short period of time and rely on internal back-up batteries.
TOTAL ARTIFICIAL HEART
The CardioWest Total Artificial Heart (CardioWest Technologies, Inc., Tucson, AZ) is a device derived from the Jarvik 70 TAH pump and subsequently modified into the Symbion (7) Can function as biventricular support and complete replacement of native heart function. The pneumatic device is implanted into the chest cavity of critically ill patients with a minimal body surface area of 1.7 m2. The prosthetic ventricles of the device replace the patient's native ventricles and connections are made to the patient's great vessels and atrial cuffs. The patients require chronic anticoagulation. Those who are eligible to receive the device must have large chests with 10-cm anteroposterior diameter at T10. The overall survival of patients on the device has been as high as 83% with a low postoperative stroke rate of 0.6 events/patient-year. The CardioWest pump should be considered in a patient with biventricular failure and a large chest cavity. The lack of a small portable controller does limit ambulation on this device. (7,8,9,10)
Another device showing much promise is the AbioCor (ABIOMED Inc, Danvers, MA) totally implantable artificial heart. The pump is an electrohydraulically actuated device implanted in the pericardial space after excision of the native heart. The pump chambers are sutured to atrial tissue and great vessels by textured Dacron atrial cuffs and grafts. Two polyurethane blood pump chambers with a 60-mL stroke volume produce 8 L/min of flow. The pump is connected to internal components including controller, battery, and transcutaneous energy transfer (TET) coil. (7,9) The patients require chronic anticoagulation after implantation to prevent thromboembolic events.
Limitations of currently available VADs (6,7,8):
Risk of thromboembolic events
Risk of infection, especially due to percutaneous control or drive lines
Large device size
Right ventricle failure
Limited physiological control strategies during prolonged use
Uncertainty about the long-term consequences of non-pulsatile flow
Adverse effects on gastrointestinal system with abdominal wall device placement
Substantial invasive surgery
Some limitations are common to most of the VADs currently available (e.g., risks of thromboembolism and infection, invasive surgery, and costs). The issues of durability, size, and gastrointestinal system problems are generally more closely associated with pulsatile flow VADs, while the issues of control strategies and non-pulsatility are commonly associated with continuous flow VADs.
The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial was conducted to compare long-term implantation of left ventricular assist devices (LVADs) with optimal medical management for patients in end-stage heart failure who require, but do not qualify to receive, heart transplantation. Results indicated that end stage heart failure patients who received an LVAD device (HeartMate XVE LVAS), destination therapy patients, had a 52.1% chance of surviving one year, compared with a 24.7% survival rate for patients who took drugs and were medically monitored. At two years, the likelihood of survival was 22.9% for the LVAD patients versus 8.1% for those receiving medical therapies. However, because of this relatively poor two-year survival despite LVAD therapy, use of destination therapy has remained rare and efforts were directed at improving pump technology.(5,9,10) Survival would likely have been better if the destination therapy patients were less severely ill at the time of implantation.
The LVAD Working Group (LWG) study is a multicenter study attempting to better classify who will benefit from using LVADs as a bridge to recovery/remodeling, since LVADs have been shown to cause a reversal of ventricular chamber enlargement, reduction of left ventricular mass, regression of myocyte hypertrophy, increased contractile properties of myocytes, and normalization of gene expression encoding for proteins involved in calcium metabolism in the failing heart, and what parameters are to be used to wean the patient off the LVAD (7) Specific and unique pharmacotherapy may also prove to be beneficial in this patient population with the resulting treatment formula being a combination of device implantation and pharmacologic manipulation
The Investigation of Non-Transplant-Eligible Patients Who Are Inotrope Dependent (INTREPID) trial is another similar study currently under way and near completion. This study involves the Novacor LVAS, which has been shown to work without failure an average of 4 years in 12 patients. (11) The results of this study may further reconfirm the LVAD as an alternative to transplantation and a good tool in the fight against heart failure.
The Harefield Recovery Protocol Study (HARPS) is a clinical trial to evaluate whether advanced heart failure patients requiring VAD support can recover sufficient myocardial function to allow device removal (known as explantation.
COMPARISON AND CONTRAST OF OPTIMAL MEDICAL THERAPY AND DESTINATION VAD THERAPY
Fundamental differences emerge in the evaluation of efficacy when comparing drugs and devices. By contrast with drug development, progress with devices is more incremental, with experience leading to progressive device modifications. The impact of devices is more transparent, in part because the most obvious risks are front-loaded compared with those from new drugs. It is harder for the effects of devices to be masked or mimicked by the natural history of heart failure. (3)
Indications for advanced heart failure therapy LVAD represent a promising option as a "destination therapy" for advanced-stage heart failure patients who do not respond to conventional therapy. The following list of risk factors offers a quick reference to help the cardiologist easily identify patients who should be considered for LVAD advanced heart failure therapy. (4)
Patients with severely reduced LVEF (<30%) and:
* Inability to walk one block without shortness of breath despite optimal medical therapy (OMM = ACE inhibitor, ARB or beta blocker)
* Two hospitalizations in the past 6 months despite OMM
* Inability to tolerate (OMM) due to hypotension
* Slowly declining kidney function (i.e serum creatinine rise > 1.8 mg/dl)
Importantly, symptoms should be due to CHF and end organ damage such as renal dysfunction, liver dysfunction, and lung dysfunction should not be severe and irreversible. Therefore, for example, patients with liver cirrhosis and/or severe COPD, and/or endstage renal disease requiring dialysis are unlikely to benefit from LVAD therapy.(5,6,10)
Destination therapies intended to supplement or permanently replace the body's heart are provided by chronic implantation of the mechanical circulatory support system. Destination therapy can offer those patients not eligible for organ transplantation a promising future. VADs with success rates that can be used as a bridge to organ transplant or as destination therapy include Novacor LVAS console and wearable, TCI LVAD pneumatic and electric, Thoratec LVAD and BIVAD, CardioWest TAH. (5,10,12)
The current patient population for destination therapy is limited to those patients who have advanced NYHA class IV heart failure and are not transplant candidates or are transplant candidates but will likely not receive a transplant. Most such candidates are inotrope-dependent or supported by intra-aortic balloon pumps and have severely limited VO2 max levels in the range of 9-11 ml/min/m2.(6,4,10)
PHYSIOLOGY AND MANAGEMENT OF PULSATILE FLOW VERSUS AXIAL FLOW
The pumps used in VADs can be divided into two main categories - pulsatile pumps, that mimic the natural pulsing action of the heart, and axial flow which enables continuous flow of blood.
Pulsatile VADs use positive displacement pumps. In some of these pumps, the volume occupied by blood varies during the pumping cycle, and if the pump is contained inside the body then a vent tube to the outside air is required.(4,11,12)
Continuous flow VADs normally use either centifugal pumps or an axial flow pump. Both types have a central rotor containing permanent magnets. Controlled electric currents running through coils contained in the pump housing apply forces to the magnets, which in turn cause the rotors to spin. In the centrifugal pumps, the rotors are shaped to accelerate the blood circumferentially and thereby cause it to move toward the outer rim of the pump, whereas in the axial flow pumps the rotors are more or less cylindrical with blades that are helical, causing the blood to be accelerated in the direction of the rotor's axis (4,11,12) Early clinical experience has shown that long-term nonpulsatile blood flow is well tolerated. (12)
Pulsatile Pumps include:
Novacor, HeartMateXVE, C-Pulse, Thoratec PVAD, Thoratec IVAD, Arrow LionHeart LVD-2000
Axial Pumps include:
HeartMateII, HeartMate III, Incor, Jarvik 2000, MicroMed-DeBakey VAD, Ventr Assist, MTIHeartLVAD,
With continued evolution of devices, management, and patient selection, outcomes approaching those of heart transplantation may be possible.(3,6) Innovative translational medical research, including use of high-throughput genomics, will potentially improve patient selection and might ensure a better survival.(4,6) Each device currently in clinical use, or under development, has limitations already recognized to retard or jeopardize clinical use. The potential of these devices not only as a bridge to transplantation but also as destination therapy is being shown in clinical trials. A number of devices are currently under development and will soon reach clinical application.. (7)
The HeartSaver LVAD (World Heart Corporation, Ottawa, ON, Canada) is designed as a totally implantable LVAD system using TET coil for transcutaneous energy transfer.
Thoratec Intracorporeal VAD
The Thoratec Intracorporeal VAD (Thoratec Laboratories Corp., Pleasanton, CA) is being designed by the same firm that developed the paracorporeal device.
Novacor II (World Heart Corp., Ottawa, ON, Canada) is a concept heart created by a company with extensive LVAD experience. It will be a totally implantable pump for definitive treatment of heart failure.
The next generation of centrifugal pumps will be implantable circulatory assist devices. The HeartQuest System (MedQuest Products Inc., Salt Lake City, UT) is one such pump built on the maglev (magnetic levitation) concept, which allows for frictionless pumping, low thrombogenicity, minimal noise and vibration, and durability due to lack of metal to metal contact. These pumps have been tested in animals with promising results.(2) Current short-term pump manufacturers include Biomedicus (Medtronic Biomedicus, Minneapolis, MN), Sarns (Sarns Inc/3M, Ann Arbor, MI), Gyro Pump (Baylor College of Medicine, Houston, TX), Rotodynamic pump (Cleveland Clinic Foundation, Cleveland, OH). Displacement pumps are most frequently used in adults. They are classified as intracorporeal or extracorporeal.