Total Artificial Heart 

The total artificial heart (TAH) is used to provide complete circulatory support in patients who are awaiting cardiac transplantation.

In patients who develop irreversible biventricular failure and face imminent death, implantation of the TAH has been shown to improve survival and adequately stabilize this group of challenging patients awaiting cardiac transplantation.

Heart failure

Heart failure is common in the United States and Europe, affecting nearly 20 million people. In the United States, an estimated 600,000 new cases of heart failure are diagnosed each year, and an estimated 100,000 patients are diagnosed with advanced heart failure.^[1] Treated medically, advanced heart failure with New York Heart Association (NYHA) class IV and American Heart Association (AHA) stage D symptoms is associated with a 1-year mortality rate of 60%-94%.^[2]

Cardiac transplantation represents the most effective long-term treatment strategy for advanced heart failure; however, the supply of donor hearts is limited to only 2,100 annually, a figure that has remained constant over the last 20-30 years.^[3] Mechanical circulatory support (MSC) devices are currently being surgically implanted to address a wide spectrum of cardiac dysfunction in the form of (1) partial circulatory support using ventricular assist devices (VAD) or (2) complete circulatory support with a TAH in patients who are awaiting cardiac transplantation.

History of the total artificial heart

Formal development of the TAH began in 1964 after the National Institutes of Health launched an artificial heart program culminating in the development and implantation of the first TAH in a human by Domingo Liotta and Denton Cooley at the Texas Heart Institute in 1969.^[4]

In 1982, researchers at the University of Utah developed the Jarvik-7 TAH, which was surgically implanted by William DeVries with the intention of permanently sustaining life in a human. The device was implanted into a patient named Barney Clark, who survived 112 days.^[5]

Another milestone was reached in 1985 when Jack Copeland and colleagues successfully implanted the Jarvik-7 TAH for bridge-to-transplantation (BTT) indications; by 1988, over 100 patients had received the Jarvik-7 TAH. Of these 100 patients, 68 survived to reach cardiac transplantation.^{[6, 7]}

In 1993, CardioWest Technologies acquired the rights and technologies for the Jarvik-7 TAH, renaming it the CardioWest TAH, and obtained an Investigational Device Exemption (IDE) from the FDA to begin a clinical trial for BTT indications.^[8]

Concurrent development of a TAH with a novel design, named the AbioCor TAH, underwent phase I clinical trials beginning in 2001. However, the study included only 14 patients and still remains in the early stages of clinical development.^[8]

In 2003, the CardioWest TAH received the CE mark in Europe and, in 2004, became the first TAH to gain FDA approval for BTT indications in the United States.^[9]

In 2010, the CardioWest TAH was officially renamed the SynCardia temporary TAH.

Category

Total artificial heart

Device details

SynCardia total artificial heart

AbioCor total artificial heart

SynCardia total artificial heart

The SynCardia total artificial heart (TAH) is a pulsatile, biventricular, pneumatically driven, orthotopic TAH that replaces some of the recipient atrial tissue, all 4 cardiac valves, both ventricles, and the proximal portions of the aorta and pulmonary arteries.

Each ventricle has a polyurethane diaphragm that separates blood from air. Medtronic-Hall mechanical valves in the atrioventricular and the semilunar positions (27 mm inflow and 25 mm outflow) provide unidirectional blood flow. Maximum stroke volume is 70 mL, and maximum cardiac output is 9.5 L/min. Total weight is 160 g with a volume displacement of 400 mL. A pneumatic driveline is connected to each ventricle, which is tunneled through the chest wall and connected to an external console.^[10]

The large external console, nicknamed "big blue," has, until recently, been used for in-hospital use only. However, in 2010, the FDA approved an IDE study allowing use of a portable driver, a 13.5-lb wearable piston-driven pneumatic compressor, which is currently ongoing.^[9]

AbioCor total artificial heart

The AbioCor TAH is a fully implantable, biventricular, orthotopic, pulsatile electrohydraulic TAH that is driven by a battery-powered motor. The motor powers an internal centrifugal pump, which hydraulically moves a membrane sac responsible for the pumping action.

The AbioCor TAH replaces recipient atrial tissue, all 4 cardiac valves, both ventricles, and the proximal portions of the aorta and artery. The pump and valves are made from titanium and proprietary polyurethane. A miniaturized internal electronics package monitors the pumping speed.

An internally implantable battery is continuously recharged from an external power source by a process called transcutaneous energy transmission (TET), which obviates the need for percutaneous power or pneumatic drive lines.^[11] An external battery pack with a TET coil provides 2-4 hours of use, while the internal battery allows 30 minutes of tether-free operation.

The AbioCor TAH weighs 1090 g and has a volume displacement of 800 mL, making it significantly larger and heavier than the SynCardia TAH.

The AbioCor TAH received FDA Humanitarian Device Exemption in 2001 for a limited phase 1 clinical trial and is still in the early stages of clinical testing.^{[8, 12]} Given the paucity of clinical trial data, the AbioCor TAH is not discussed further in this article.

The SynCardia total artificial heart (TAH) is the only FDA-approved TAH in the United States for in-hospital BTT patients who have irreversible biventricular failure and imminent risk of death.^[9]

The selection criteria (inclusion and exclusion) from the clinical trial which led to FDA approval are discussed below.^[13]

FDA-approval inclusion criteria

Inclusion criteria were as follows:

1. Eligible for cardiac transplantation (according to institutional criteria)

2. New York Heart Association class IV symptoms

3. Body surface area of 1.7-2.5 m² or a distance of 10 cm or more from the anterior vertebral body to the inner table of the sternum at the 10th thoracic vertebra on CT scanning

4. Hemodynamic insufficiency according to either of the following definitions:

• Cardiac index of 2 L/min/m² or less and one of the following: (1) systolic arterial pressure of 90 mm Hg or less or (2) central venous pressure of 18 mm Hg or more
• Two of the following: (1) dopamine at a dose of 10 µg/kg/min or more, (2) dobutamine at a dose of 10 µg/kg/min or more, (3) epinephrine at a dose of 2 µg/kg/min or more, (4) isoproterenol at more than 2 µg/kg/min, (5) amrinone at more than 10 µg/kg/min, (6) other cardioactive drugs at maximal doses, (7) use of an intraaortic balloon pump, or (8) use of cardiopulmonary bypass

FDA-approval exclusion criteria

Exclusion criteria were as follows:

• Use of any ventricular assist device
• Pulmonary vascular resistance of 8 Woods units or more (640 Dynes-sec/cm⁵)
• Hemodialysis during the previous 7 days
• Serum creatinine level of 5 mg/dL or more
• Cirrhosis with total bilirubin levels of 5 mg/dL or more
• Cytotoxic antibody of 10% or more

Contraindications

Based on a summary of safety and effectiveness data by the FDA, contraindications to TAH include the following:^[14]

• Patients who are not eligible for cardiac transplant
• Patients who do not have sufficient space in the chest area vacated by the natural ventricles; this generally includes patients who have body surface areas of less than 1.7 m² or who have a distance of less than 10 cm between the sternum and the anterior vertebral body measured by CT scanning
• Patients who cannot receive adequate anticoagulation on the TAH

Safety and efficacy of the SynCardia total artificial heart (TAH) was assessed in a nonrandomized, prospective, multicenter clinical trial conducted from 1993-2002 by Copeland and colleagues. This trial included 130 patients, 81 who received the TAH after meeting study protocol-inclusion criteria, and 35 controls who were clinically matched with the protocol group but did not receive the TAH device. Primary endpoints were rate of survival to cardiac transplantation, overall survival, and survival after transplantation.

Survival to transplantation among TAH recipients compared to the control group was 79% versus 46%, 1-year overall survival was 70% versus 31%, and 1- and 5-year posttransplantation survival rates among patients receiving the TAH as a BTT was 86% and 64%, respectively. This compared favorably to United Network of Organ Sharing (UNOS) statistics at 1 and 5 years after transplantation of 84% and 69%, respectively.^[13]

Leprince et al in France conducted the largest single-center TAH study. They retrospectively reviewed 127 TAH implants from 1986-2001 and found that 64% of patients survived to cardiac transplantation.^[15]

Interestingly, in a more recent update, Slepian reported that a single US center implanted 48 TAHs since 2006, achieving a BTT success rate of greater than 95%.^[9]

More than 900 total artificial hearts (TAHs) have been implanted in over 40 medical centers throughout the United States and Europe.^[9]

According to INTERMACS data current through 2009, 69% of TAH recipients were successfully bridged to transplantation, in contrast to 35% of patients receiving biventricular assist devices (BiVAD). Furthermore, patients undergoing TAH implantation represented a sicker cohort, with 92% of patients being INTERMACS level I and II, while 73% of patients in the BiVAD cohort were considered at this level.^{[16, 9]}

No randomized prospective clinical trials have compared TAH with BiVAD or LVAD. Copeland et al performed a retrospective risk factor analysis for BTT using the TAH with multivariate analysis and showed that only a history of smoking was associated with increased mortality. Common independent risk factors for mortality in patients receiving left ventricular assist devices (LVAD) or BiVAD were not found to predict mortality in patients undergoing TAH implantation.^[17]

Implantation of the TAH by Copeland and colleagues resulted in immediate improvement in hemodynamic parameters, with sustained increase in cardiac index from a baseline of 1.9 L/min/m² to 3.2 L/min/ m², improved mean systolic blood pressure from 93 mm Hg to 122 mm Hg, and decreased mean central venous pressure from 20 mm Hg to 14 mm Hg.^[13] Renal and hepatic function returned to normal values within 4 weeks after TAH implantation.^{[13, 18]} However, quality of life improvements were not objectively quantified based on current studies. Mobility as measured by ability to walk more than 100 ft 2 weeks after implantation was observed in 60% of patients.^[13]

Kohli et al demonstrated the safety of a structured approach to physical rehabilitation with ambulation beginning in the intensive care unit a median of 5 days following TAH implantation, advancing to treadmill exercise at a median of 19 days.^[19] Duration of TAH support from a major clinical trial showed a mean duration of 92 days with a maximum documented duration of TAH support of 832 days.^{[13, 18, 20]} Durability of the SynCardia TAH is well documented, with a low incidence of device complication or failure.^{[9, 13, 18]}

Currently, patients who receive the TAH must remain in the hospital until a suitable donor organ becomes available for transplantation. In accordance with UNOS policy, patients who are clinically stable after receiving the TAH are moved to the top of the cardiac transplant list as status 1A for a period of 30 days.^[21]

In March 2010, the FDA approved an IDE study to assess the safety and feasibility of the portable driver in clinically stable patients in the outpatient setting.^[9]

Technical considerations

Techniques for TAH implantation are briefly summarized by Copeland and colleagues.^[22]

A standard median sternotomy is performed and pneumatic drivelines are tunneled subcutaneously prior to heparin administration. The native heart is then removed on the ventricular side of the atrioventricular groove with preservation of the atrioventricular annulus. Great vessels are then transected above the sinotubular junction. Next, left and right atrial cuffs are encircled with felt buttresses and then sewn into atrial inflow connectors.

Sheets of Gore-Tex membrane are then fashioned posteriorly to function as a neo-pericardium and to ease explantation of TAH at the time of cardiac transplantation. TAH ventricles are then lowered into position and connected to the great vessels with outflow connectors and to the atria with inflow connecters. All anastomoses are systematically tested for leaks.

Steep Trendelenburg is then applied, and TAH pumping is begun at a slow rate of 40 bpm until the deairing process is complete. Transesophageal echocardiography is used to ensure complete deairing, to monitor hemodynamics when up-titrating the device heart rate, and to position the device upon chest closure.

A multidrug anticoagulation regimen is begun after chest tube output is less than 30 mL/hr for 4 consecutive hours.

Because the FDA guidelines have mandated the use of the total artificial heart (TAH) for in-hospital BTT indications only, no guidelines currently exist for outpatient follow-up care. The TAH is not FDA-approved for destination therapy indications.

Anticoagulation to prevent device-related malfunction and clinical events related to thrombus formation must be used in all patients receiving a TAH. Coagulation testing is performed in all patients to individualize timing, type, and degree of anticoagulation. In general, a multidrug anticoagulation strategy involving heparin, warfarin, aspirin, dipyridamole, and pentoxifylline is necessary.^{[15, 18]} Bleeding from acquired von Willebrand syndrome has not been demonstrated in patients receiving the pulsatile TAH as compared with continuous-flow mechanical assist devices.^[23]

Meticulous percutaneous driveline care is warranted to ensure tissue ingrowth around drivelines postoperatively and to surveil for early infection.

Results from the ongoing FDA-approved IDE trial using the smaller portable driver will lead to a better understanding of TAH use in an outpatient environment and will lead to the development of monitoring protocols. In fact, SynCardia is developing a remote monitoring system feature in the next generation of portable drivers.^[9]

Copeland et al reported multiple adverse events in 81 patients receiving the total artificial heart (TAH) in the FDA-approval trial; bleeding (62%) and infection (77%) were most common. Most bleeding (54%) occurred in the immediate postoperative period and required reoperation (28%) due to mediastinal bleeding or (atrial) tamponade. Infections were common and multifactorial in etiology, with respiratory (40%), genitourinary (22%), and driveline infections (14%) being most frequent. Interestingly, in 84% of patients in the protocol group, these infections did not delay transplantation or cause death.^[13]

Leprince et al retrospectively analyzed 127 patients receiving the TAH in France between 1986 and 2001. Although the study cohort was heterogeneous owing to patient selection and treatment differences, the most common complications associated with TAH implantation included multiorgan failure, infection, and bleeding.^[15]

Stroke or transient ischemic attack (TIA) occurred in 19% of patients in the FDA-approval trial, but most occurrences led to no or minimal residual neurological deficits after 48 hours.^[13] Leprince et al demonstrated a very low stroke rate in the largest reported cohort of patients receiving the TAH, with a clinical neurologic event rate of 0.2 events per patient-year. This very low thromboembolic event was explained by the elimination of native cardiac tissue and intrinsic design of the TAH, use of a single anticoagulation protocol, and use of a designated physician to monitor each patient’s anticoagulation profile.^[15]

Only one major device malfunction resulting in patient death in the FDA approval trial occurred during more than 12,000 patient-days of TAH support.^[13] In the French series, only one TAH device malfunction was reported in 3,606 total implant days.^[15]