Chapter 67. Total Artificial Heart

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and a significant public health problem in most industrialized nations. Since 1900, it has been the leading cause of death in the United States every year except 1918.1 In 2005, CVD afflicted 80 million Americans and caused 864,500 deaths. Meanwhile, the number of people with CVD, and especially its advanced forms, has been increasing. There are two main reasons for this. First, although there is still no cure for CVD, palliative therapy has improved to the point that more people are surviving past their initial episodes of CVD to live on with some form of the disease. Second, the average age of the US population is rising as the “baby boom” generation ages.

An increasingly prevalent form of advanced CVD is heart failure (HF). Almost 5.7 million Americans (approximately 3.2 million men and 2.5 million women) are living with HF.1 Its etiology can be ischemic, idiopathic, or viral. More than $37.2 billion is spent each year on the care of HF patients, and many therapeutic advances have been made. In 2005, HF directly caused 53,000 deaths and indirectly caused another 250,000. As large as the problem is now, its magnitude is expected to worsen as more cardiac patients are able to survive and live longer with their disease and thus increase their chances of developing end-stage HF.

At present, treatment of advanced HF takes three forms: medical therapy, surgical therapy, and cardiac support or replacement.2,3 Medical therapy (eg, intravenous inotropes and vasodilators) relieves symptoms by reducing cardiac work and increasing myocardial contractility. However, although advances in medical therapy have helped improve quality of life for those with heart failure, mortality remains unaffected. Surgical therapy (eg, revascularization and valve replacement or repair) relieves symptoms of ischemia and valvular dysfunction, but in most cases does not stop the underlying disease process from progressing. When conventional medical and surgical therapies for HF are exhausted, cardiac support or replacement (ie, heart transplantation or implantation of an artificial heart or ventricular assist device) may in some cases become the only therapeutic alternative.

Heart transplantation has evolved into a suitable treatment for advanced HF. However, it has severe limitations related to patient selection, organ procurement and distribution, and cost-effectiveness. Slightly more than 2000 patients with end-stage heart failure receive heart transplants each year in the United States. However, about 3000 patients are on the active heart transplant waiting list at any given time, and as many as 40,000 more are potential candidates for heart transplantation.4,5 Heart transplantation for the relatively young (<40 years old) is not very promising because the life expectancy of a donor heart recipient is about 10 years on average and 20 years at most. In 2004, 460 patients on the active waiting list died while awaiting a donor heart. Heart transplantation is also associated with continuous, lifelong, expensive medical therapy.

To help overcome these limitations, engineers and physicians have continued efforts begun over four decades ago to develop systems for providing either temporary or permanent mechanical circulatory support (MCS). Originally, such systems were intended to support patients indefinitely because other forms of heart replacement did not appear to be feasible. Temporary MCS has been shown to be a suitable option for some HF patients who are awaiting heart transplants.6,7 and for others who are not transplant candidates but need support for indefinite periods.8 In recent clinical studies, myocardial function improved sufficiently in some cases to allow removal of the MCS device and avoid heart transplantation.9,10 Nevertheless, in light of the shortcomings of medical therapy, surgical therapy, and heart transplantation, efforts have continued to develop a total artificial heart (TAH) that would not only save the lives of critically ill HF patients but also allow them to resume relatively normal lifestyles. Here, we review the historical development and current status of TAH technology.

In 1812, LeGallois first proposed the idea of supporting a failing heart with either a permanent or temporary device.11 In the 1920s, Lindbergh and Carrel discussed and planned an artificial heart.12 Throughout the 1940s researchers including Dennis and Gibbon were developing a machine that would bypass the circulation of the heart and lungs to allow open-heart surgery. The modern era of MCS began in 1951 when Dennis first used a heart-lung machine to sustain the circulation while the heart was opened to repair an atrial septal defect.13 Two years later, Gibbon repeated this procedure.14 However, high mortality in the first few cases led both Dennis and Gibbon to abandon the use of their heart-lung machines. In 1954, Lillehei began to use cross-circulation (human-to-human perfusion) as a means to support heart and lung function during congenital heart defect.15 However, because of the controversy created by Lillehei's procedure, researchers continued efforts to develop a machine that would allow open-heart surgery.

By 1955, Kirklin and associates at the Mayo Clinic had refined the Mayo-Gibbon machine and the techniques that allowed open-heart surgery.16 Likewise, Lillehei and associates had developed their machine that also allowed for safe open-heart operations.17 By 1960, Kirklin and Lillehei in Minneapolis and DeBakey and Cooley in Houston had perfected their machines and techniques to the point where heart surgery was becoming routine in Minnesota and Texas. The early developmental work on the use of mechanical circulatory systems by Dennis, Lillehei, DeWall, Gibbon, and Kirklin allowed for many new cardiac operations, including coronary artery bypass, heart transplantation, valve repair, and implantation of a TAH. After refinements of the heart-lung machines, DeBakey and Cooley began to develop many of the surgical techniques that eventually made open-heart surgery routine around the world.

In 1957, Akutsu and Kolff became the first to implant a TAH in vivo.18 Inserted into the chest of a dog, the pump adequately maintained the circulation for approximately 90 minutes. However, Akutsu and Kolff never applied their TAH technology clinically. In 1964, the National Heart Institute established the Artificial Heart Program to promote the development of the TAH and other cardiac assist devices. In the early 1960s, DeBakey and researchers at Baylor College of Medicine in Houston began developing a TAH. In 1963, DeBakey implanted the first clinical left ventricular assist device (LVAD) into a 42-year-old patient.19 The pump functioned well, but the patient died of pulmonary complications after 4 days of support. In 1967, DeBakey implanted an LVAD into a 37-year-old who presented with symptoms of HF, including easy fatigability and severe dyspnea on slight exertion. This patient also had history of rheumatic heart disease since age 18 and closed mitral valvulotomy at age 25. The intention was to use the LVAD until sufficient myocardial recovery could be gained. The LVAD supported the patient's circulation for 10 days and was then electively removed. The patient was discharged from the hospital on postoperative day 29 and later resumed normal activity. On follow-up at 18 months after LVAD removal, the patient remained free of HF symptoms, and a chest x-ray showed a significant reduction in cardiac size.

The first implantation of a TAH into a human was done by Cooley on April 4, 1969, in a 47-year-old man who could not be weaned from cardiopulmonary bypass (CPB) following left ventricular aneurysmectomy.20 The intent was to support the patient until a donor heart could be found. The TAH (Fig. 67-1), designed by Liotta, was a pneumatically powered, double-chambered pump with Dacron-lined right and left inflow cuffs and outflow grafts. Wada-Cutter hingeless valves controlled the direction of blood flow through the pump. The TAH itself was connected to a large external power unit, which unfortunately severely restricted patient mobility. The TAH performed adequately for 64 hours until transplantation. The donor heart also functioned well, but the patient died of pseudomonal pneumonia 32 hours after transplantation. Though the Liotta device performed as designed, it was never used clinically again. Nevertheless, this case clearly demonstrated that a TAH could be used safely and effectively in a human as a bridge to transplantation.

The second implantation of a TAH in a human was also done by Cooley. On July 23, 1981, Cooley implanted the Akutsu-III TAH into a critically ill 26-year-old man who suffered heart failure after undergoing coronary artery bypass surgery for severe arteriosclerosis. Unable to be weaned from CPB after surgery, the patient was fitted with the TAH in a final effort to sustain his life. The Akutsu-III TAH (Fig. 67-2) consisted of two pneumatically powered, double-chambered pumps featuring reciprocating hemispherical diaphragms.21 The TAH provided excellent hemodynamics and supported the patient in stable condition for a total of 55 hours until a suitable donor heart was found. The patient finally received a transplant but died of infectious, renal, and pulmonary complications 10 days later. Despite the fatal outcome, this case demonstrated that a TAH could adequately sustain a patient for several days, with no evidence of hemolysis or thromboembolism, until heart transplantation.

In the late 1970s, Kolff and his team at the University of Utah developed the Jarvik-7 TAH. In 1982, DeVries became the first to permanently implant a TAH when he implanted a Jarvik-7 into a dying patient.22 The Jarvik-7 TAH (Fig. 67-3) was a pneumatically powered, biventricular pulsatile device that replaced the heart.23,24 The pumps were connected to their respective native atria by synthetic cuffs and connectors. Each pump had chambers for air and blood separated by a smooth, flexible polyurethane diaphragm. The inflow and outflow conduits contained Medtronic-Hall tilting disk valves. The filling of the pumps was aided by vacuum. Pneumatic drivelines, brought out through the chest wall to connect with an external console, shuttled air to the pumps during systole, thereby causing collapse of the pump sac and blood ejection. Pump rate, drive pressure, and systolic duration were monitored and optimized from the external console. The Jarvik-7 had a stroke volume of 70 mL and a normal cardiac output of 6 to 8 L/min (maximum, 15 L/min).

In the initial clinical experience with the Jarvik-7 TAH, a total of five patients were permanently supported for periods ranging from 10 to 620 days. The TAH was able to adequately support circulation, but its large drive console and frequent medical complications limited patient activity. Four patients were able to make brief trips out of the hospital to see family and friends. Long-term outcomes, however, were poor. Patients supported by the Jarvik-7 for longer periods suffered several complications, including thromboembolism, stroke, infection, and multiorgan failure.

Despite these mixed results, in 1985 the Jarvik-7 (renamed the Symbion) TAH entered clinical trials as a bridge to transplantation. In 1986, Copeland reported the first successful use of this device for this indication.25 Between 1985 and 1991, approximately 170 patients were supported with the Symbion TAH as a bridge to transplantation.26 Sixty-six percent underwent successful heart transplantation, a rate similar to those in bridge-to-transplantation studies of left ventricular assist devices. Sepsis and multiple organ failure were the primary causes of death during TAH support.

Although the bridge-to-transplantation study demonstrated that the Jarvik-7 (Symbion) TAH was clinically safe and effective, the US Food and Drug Administration (FDA) withdrew the device's investigational device exemption (IDE) for clinical use in January 1991 because of inadequate compliance with FDA regulations.27 In January 1993, the IDE was restored to the CardioWest TAH, which differed little from the original Jarvik-7. In 2001, Syncardia, Inc. was formed, and the CardioWest TAH-t (temporary) has since been used successfully in the United States, Canada, and France.28 In the US clinical trials, survival to transplantation and overall 1-year survival rates were significantly higher for CardioWest TAH-t recipients (n = 81) than for controls (n = 35) (79% versus 46% and 70% versus 31%, respectively). These results led to market approval of the CardioWest TAH-t as a bridge-to-transplant device in 2004. By 2009, more than 800 implants have been performed at more than 40 centers worldwide.

On July 2, 2001, as part of an FDA-sponsored phase I clinical trial, surgeons at Jewish Hospital in Louisville, Kentucky, performed the first implantation of the AbioCor TAH in a 59-year-old man with end-stage HF.29 The AbioCor Implantable Replacement Heart is a self-contained, electrohydraulic TAH (Fig. 67-4) that has been developed and tested by ABIOMED, Inc. (Danvers, MA) and the Texas Heart Institute, with the support of the National Heart, Lung, and Blood Institute (NHLBI).30,31 It is designed to sustain the circulation and extend the lives of patients with end-stage HF who have suffered irreversible left and right ventricular failure, for whom surgery or medical therapy is inadequate, and who would otherwise soon die (Table 67-1). The AbioCor is the first TAH to be used clinically that is fully implantable and communicates to external hardware without penetrating the skin. The device utilizes a transcutaneous energy transfer system (TET) and a radiofrequency communication (RF Comm) system that allows it to be powered and controlled by signals transmitted across intact skin. A unique feature of the AbioCor is a right-left flow-balancing mechanism that eliminates the need for an external vent or internal compliance chamber.32

The internal components of the AbioCor system consist of a thoracic unit, internal TET coil, controller, and battery.33 The thoracic unit (pump) weighs about 2 lb and consists of two artificial ventricles, four valves, and an innovative motor-driven hydraulic pumping system (Fig. 67-5). The pump's motor rotates at 6000 to 8000 rpm, which allows sufficient hydraulic fluid pressure to compress the diaphragm around the blood chamber and eject blood. A miniaturized electronics package implanted in the patient's abdomen monitors and controls the pump rate, right-left balance, and motor speed. An internal rechargeable battery, also implanted within the abdomen, provides emergency or backup power. The internal battery is continually recharged via the TET system and can provide up to 30 minutes of untethered operation.

The AbioCor's external components include a computer console, an external TET coil, and external battery packs. The external computer communicates via the RF Comm system with the abdominally implanted controller, which controls the pump. The external TET coil provides the pump with power from the console or from the external battery packs. The external battery packs can power the AbioCor TAH for 2 to 4 hours (Fig. 67-6).

In the phase I feasibility trial, 14 patients received the AbioCor as destination therapy (Table 67-2). Thrombo-embolism was a significant adverse event in this group of patients, and there were two pump failures. However, compared with the known rates of infection for implantable systems with percutaneous drivelines, device-related infections in this trial were relatively rare. The longest surviving patient was supported for 512 days, most of which were lived at home with a good quality of life. In 2006, the FDA approved the AbioCor for commercial use under a Humanitarian Device Exemption.

Use of a TAH is associated with serious complications. The most frequent complications are infection, severe postoperative bleeding, and thromboembolism.34-37 Potentially serious but less frequent complications are renal, hepatic, pulmonary, and neurologic dysfunction and complications caused by technical problems.34,38 Complicating factors include patient selection, device size, implantation timing and location, the need for extensive surgery at implantation, and the reliability of support equipment.

Life-threatening infections have been the most important complication for patients being supported permanently by a TAH.39 In the Jarvik-7 experience, all patients supported for many months developed serious infections that eventually contributed to their deaths.23,40 Patients supported by a TAH for shorter periods while awaiting heart transplantation had infection rates of 30 to 40%.35-39 During the 1980s, driveline and mediastinal infections in TAH-supported patients were frequent and severe, regardless of the duration of support. However, in the more recent bridge-to-transplantation experience with the CardioWest TAH-t, serious infections contributing to death or delayed transplantation occurred in only 21% of patients.41,42

Patients supported with a TAH, regardless of the intended use, are very susceptible to infection. Predisposing factors include the tissue trauma associated with surgical implantation; contamination of the implanted device; depression of the body's immune defenses; the large amount of foreign material presented on the surface of the device; and use of the drivelines, tubes, catheters, and other devices that are necessary for the care of these patients. Infections can occur at any point during TAH support. Once an internal component of the TAH system is infectiously colonized, treatment is difficult and often ineffective. Infections are more likely to occur in the early postoperative period, especially in the most critically ill patients, as a result of (1) device contamination during the course of care and (2) postoperative bleeding caused by intensive care procedures and exposure during reoperation. Meticulous care and numerous infection prevention measures are vital in all TAH patients.

Postoperative bleeding is a frequent and serious complication of TAH implantation. It generally occurs in 40 to 50% of TAH or ventricular assist device recipients.34 In the more recent CardioWest TAH-t experience, the rate was approximately 25%. Contributing factors include severe HF and associated hepatic dysfunction, the extensive surgery and lengthy CPB time required for implantation, and the necessity for postoperative anticoagulation therapy. Severe HF often leads to hepatic dysfunction and subsequent derangement of the coagulation system. Patients with severe HF are often receiving continuous preoperative anticoagulant or antiplatelet therapy, the effects of which are often difficult to reverse before TAH implantation. The extensive surgery and lengthy CPB time required for implantation can lead to severe depletion of clotting factors. The necessity for postoperative anticoagulation therapy requires that a proper balance be established between preventing thrombosis and allowing blood to clot, through the careful management of hemostasis and anticoagulant therapy.

Thrombosis within the TAH is of particular concern. Five of the first six Jarvik-7 recipients had thromboembolic events. However, the frequency of thromboembolism has decreased significantly since that initial experience and is now an estimated 10 to 15%.34,35,43 Preventive measures are primarily targeted at precisely monitoring the thrombotic and fibrinolytic systems, maintaining sufficient flow through the device to avoid stasis, and providing adequate anticoagulation and antiplatelet therapy. Generally, heparin and warfarin are used as antithrombotic therapy to achieve a prothrombin time, activated thromboplastin time, or international normalized ratio two to three times greater than the baseline or normal value. Aspirin or dipyridamole or both are also used.

There is a complex though poorly understood interrelationship between infection, bleeding, and thromboembolism. Thrombus formation may lead to the development of infection, and bacterial colonization may lead to thrombus formation. Bacteria are often seen in thrombi found in cardiovascular devices.44 Bacteria embedded in a thrombus are protected from circulating antibiotics and leukocytes. Bacteria, endotoxins, and inflammatory cells may contribute to thrombus formation by their effect on platelet aggregation.44 Bacterial endotoxins can cause platelet aggregation, endothelial injury, and increased endothelial thromboplastin activity. Excessive bleeding most often results in reoperation, which increases the patient's exposure to contamination. Also, blood transfusions and intravascular monitoring for these critically ill patients are more extensive and result in frequent exposure to the external environment. Infection, bleeding, and thromboembolism can contribute individually and collectively to the development of multiple organ failure, one of the most frequent causes of death in TAH recipients.

Other important problems and issues related to TAH implantation are device malfunction, poor fit or size mismatch between TAH and patient, social and ethical issues, mobility, and nutrition. Device malfunction leading to catastrophic failure of the TAH or ventricular assist device is rare. Most technical issues have involved external components and have been readily resolved. Fit and size mismatch remains a problem. All TAH models used to date have been relatively large and only fit adequately into patients with a body surface area greater than 1.7 m2. Because the cost of TAH technology is fairly high and most candidates for TAH implantation are in their sixth to seventh decade of life, many groups question whether society should bear the cost of developing this technology. Until recently, the external components of the TAH equipment have been large and cumbersome, thus limiting patient mobility, exercise, and rehabilitation. More recent designs of the TAH allow for much more mobility.

It has been shown that HF can be treated with volume-displacement TAHs, such as the pneumatic CardioWest TAH-t or the AbioCor TAH. The CardioWest TAH-t has successfully supported patients awaiting transplantation.40,45,46 However, its externalized pneumatic drivelines and pneumatic console limit durability and patient mobility, making this TAH poorly suited for permanent cardiac replacement. The electrohydraulic AbioCor Implantable Replacement Heart has been used in a small, select group of patients requiring biventricular replacement.47 Although these TAHs have been used successfully in some patients, their large size, mechanical complexity, and poor durability have also limited their application.

Recently, new design applications using continuous-flow rotary blood pumps have emerged to create a smaller and more compact alternative to the larger volume-displacement TAHs. Unlike the pulsatile, volume-displacement TAHs, these rotary pumps have no flexible membranes, pusher-plates, or prosthetic valves that can wear out. They are actuated by rapidly spinning impellers, which reduce their mechanical complexity. Rotary pumps are more durable, making them less expensive to produce. In addition, these pumps are smaller, quieter, and more energy efficient than are volume-displacement pumps. Lastly, rotary pumps are inflow-pressure sensitive—they closely imitate the native heart by autonomously increasing pump flow in response to an increasing preload. Surprisingly, this technology has never been used clinically in a TAH configuration, despite the significant need for a cardiac replacement device (CRD) that is smaller, simpler, and less expensive. Therefore, constant-flow technology may be ideally suited for integration into the next generation of permanently implantable CRDs.

Recently, at the Texas Heart Institute, we have begun extensive testing of rotary blood pumps to assess the feasibility of using two continuous-flow pumps for totally implantable biventricular replacement.48 Axial-flow and centrifugal-type blood pumps are being developed for use as CRDs.48,49 Initially, the constant-flow pumps were designed and used clinically as left ventricular assist devices (LVADs). However, it was noted, particularly in pumps placed outside the ventricle, that the ventricle itself acted as a reservoir and that the aortic valve did not open. Therefore, technically, there was no pulse. Despite this, patients had normal physiologic function, even years after the device was implanted. This fact supports our belief that constant-flow pumps could be a feasible option for a CRD.

The use of two independent constant-flow pumps modifies and may even eliminate the need for a separate control mechanism for atrial balance. Each pump's flow will be regulated by the pressure differential between the inflow and the outflow, even at a constant rpm. Testing of that concept in our laboratory has also proved promising, with animal survival times of 7 weeks after total cardiac replacement with two rotary pumps. This was achieved by maintaining a constant rpm, even in treadmill studies. The normal physiologic response gives us some hope that an individualized flow might be assessed for each patient, without the need for a complex, integrated system. Continuous flow with an induced pulse (by modulating speed) and with pulseless flow is being investigated to study the physiologic effects in a chronic animal model.

Additional programs have also begun to investigate the use of rotary blood pumps as CRDs. The Cleveland Clinic is developing a valveless, sensorless, pulsatile, continuous-flow double-pump TAH.50 The impellers of both pumps are attached to a single axial rotor. Atrial pressures are balanced by way of passive self-regulation (the rotor axial position and subsequent position of the impeller with regard to the right pump inflow). If the atrial pressure on either the left or right sides is increased, the rotor is pushed to the contralateral side, forcing the impeller either to block or open the right inflow opening, thus increasing or decreasing right pump flow. A group at Queensland University of Technology is also working on a single-unit rotary device CRD that uses a shared rotating hub with two impellers.51 This device employs an interpump shunt (similar to a ventricular septal defect) for left-to-right atrial pressure balance, allowing blood to flow between the two pumps and beneath the pump impellers. At Tohoku University, two centrifugal pumps, each with independent control algorithms, are being tested as a CRD.52

Since the 1950s, when the heart-lung bypass machine was developed, many advances have been made in the surgical treatment of HF. Many surgical procedures considered impossible just 40 years ago are today considered routine. A classic example is heart transplantation. However, TAH technology has not evolved at the same pace. Although the first human heart transplantation and first human TAH implantation occurred within 2 years of each other, TAH implantation is still neither routine nor widely available. However, two TAHs are undergoing clinical trials at present in the United States. The CardioWest (formerly the Jarvik-7) TAH-t, which is the more widely used of the two, is now approved for use as a bridge to transplantation. The AbioCor TAH is still in the early stages of clinical testing and is likely years away from approval as an alternative to heart transplantation. However, should its unique TET system and flow-balancing mechanism prove to be reliable for extended periods of time, the AbioCor may become a widely used alternative to heart transplantation for those patients who have no other treatment options.

There are many obstacles to overcome before any TAH is widely accepted. Infection, bleeding, thromboembolism, and biocompatibility issues are serious problems that affect nearly all implantable cardiovascular devices including TAHs. Improved biomaterials, better prevention, and more effective antibiotic and anticoagulant medications may help overcome these problems. Acceptance by the public, by some critics in the health professions, and by third-party payors may be slow. Quality in manufacturing is needed to ensure reliability of TAH components. Addressing these problems will help bring the TAH more quickly into routine clinical use.

• Careful patient selection is key to long-term, successful outcomes. An institution's medical review board should approve potential candidates to ensure that only appropriate patients are selected for CRD implantation. Biventricular function should be carefully assessed in patients to rule out if they are better candidates for LVAD implantation.
• Bleeding complications can be multifactorial. Patients with poor platelet and liver function, those who undergo prolonged cardiopulmonary bypass times during the implant procedure, or those who have preoperative coagulopathies will likely have bleeding complications. Attention to detail during the TAH implant procedure can minimize bleeding complications and ensure faster recovery times.
• Infection prevention measures must be used in TAH patients. Should large, blood-contacting foreign bodies in the chest become infected, they are difficult to treat. All indwelling catheters should be replaced often to minimize the risk of infection. Cardiac replacement devices with external drivelines must be meticulously cared for to reduce the risk of infection.
• Device size and portability are important factors. The AbioCor Implantable Replacement Heart can only be used in larger patients with the appropriate thoracic dimensions. Imaging studies must be performed to ensure that the thoracic anatomy will allow for optimal device fit. The CardioWest TAH-t employs a pneumatic external driver, which may limit patient mobility and normal activity.