The heart is a muscular pump consisting of four chambers. The two lower chambers of the heart (called ventricles) supply blood and oxygen to the body and brain. Heart failure occurs when the pumping action of the heart is impaired and blood does not move efficiently through the circulatory system. The blood begins to back up, increasing the pressure in the blood vessels and forcing fluid from the blood vessels into body tissues. Depending on whether the left or right ventricle fails, symptoms may include fatigue, shortness of breath, weight gain, swelling of the legs or ankles, and/or liver congestion. Heart failure is a progressive disease that is medically managed at all stages, but which over time leads to continued deterioration in the heart’s ability to pump sufficient amounts of adequately oxygenated blood. When optimal medical management becomes inadequate to support the individual, his/her heart failure is considered to be at the end stage of the disease, and a heart transplant or mechanical circulatory support is the only remaining treatment option. The disparity between the number of individuals needing transplants and the availability of heart donors has led to the development of other ways to support the severely failing heart.
A number of different mechanical devices may be used to support the ventricles of a failing heart on either a temporary or a permanent basis. External or implantable ventricular assist devices (VADs) are used for many individuals with end-stage congestive heart failure who are waiting for transplantation. External VADs may provide univentricular or biventricular support. Implantable VADs or left ventricular assist devices (LVADs) are univentricular devices that are used to support the left ventricle. However, LVADs are usually inadequate as a bridge to transplant for individuals with severe biventricular disease. In cases of severe biventricular disease, the total artificial heart (TAH) offers hope. Currently two TAHs, the Syncardia CardioWest™ temporary Total Artificial Heart (TAH-t) and the AbioCor® Implantable Replacement Heart, are approved by the US Food and Drug Administration (FDA) and are required by the FDA to undergo post-approval studies.
SYNCARDIA™ TEMPORARY TOTAL ARTIFICIAL HEART (TAH-t)
On October 15, 2004, the SynCardia™ temporary Total Artificial Heart (formerly known as the CardioWest™ temporary Total Artificial Heart) (SynCardia Systems, Inc., Tucson Arizona) device became the first TAH to receive FDA approval. The FDA approved the SynCardia™ TAH-t as a bridge to transplantation in cardiac transplant–eligible candidates at risk of imminent death from biventricular failure. The TAH-t is a pulsating biventricular device that is implanted into the chest to replace the individual's left and right ventricles (the bottom half of the heart). The device is sewn to the individual's remaining atria (the top half of the heart). Hospitalized individuals are connected by tubes from the heart through their chest wall to a large, power-generated console that operates and monitors the device. The device provides circulatory support to an individual waiting for a donor heart and assists kidney and liver function by restoring normal blood flow. The SynCardia™ device is intended for use inside the hospital. For individuals who have end-stage heart failure who receive TAH-t as bridge to transplant, the evidence includes case series. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, treatment-related mortality, and treatment-related morbidity. Compared with VADs, the evidence for TAH-t in these settings is less robust. However, given the limited evidence from case series and the lack of medical or surgical options for these individuals, TAH-t is likely to improve outcomes for a carefully selected population with end-stage biventricular heart failure awaiting transplant who are not appropriate candidates for an LVAD. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome.
On June 26, 2014, the FDA approved the portable Freedom® Driver System for use with the Syncardia™ temporary Total Artificial Heart (TAH-t) as a bridge to transplantation in clinically stable cardiac transplant–eligible candidates who have been implanted with the TAH-t. The Freedom® Driver is a portable, wearable pneumatic device that powers the existing Syncardia™ temporary Total Artificial Heart (TAH-t) and can be used outside of the hospital setting, allowing some TAH-t individuals to return home while awaiting a suitable donor.
A prospective, nonrandomized study of 130 individuals from five heart centers was conducted from 1993 to 2002. Participation was limited to individuals who were eligible for transplant, were in hemodynamically compromised class IV congestive heart failure, and required cardioactive drugs or an intra-aortic balloon pump. Eighty-one individuals received a SynCardia™ TAH-t for bridge to transplant. An additional 35 control individuals met the inclusion criteria but did not receive a TAH-t. The overall 1-year survival rate of individuals receiving a TAH-t was 70 percent versus 31 percent for the control group. Infection and bleeding were common adverse events in the TAH-t group; however, only two related deaths were reported. One-year and 5-year survival rates after transplantation among individuals who had received a TAH-t as a bridge to human heart transplant were 86 percent and 64 percent, respectively. Device malfunction was reported in one individual who survived more than 124 days before the malfunction caused a perforated diaphragm resulting in death.
Similar results were reported by a group of European researchers who looked at the SynCardia™/Jarvik TAH over a 12-year period (the Jarvik TAH was the predecessor to the SynCardia™/Jarvik TAH). The researchers looked at 127 individuals who received a bridge to transplant with the device. The longest TAH implantation was 602 days. An additional six individuals survived more than 4 months. The authors were in agreement that the SynCardia™ device was safe and effective for bridging individuals to transplant.
ABIOCOR® IMPLANTABLE REPLACEMENT HEART
On September 5, 2006, the FDA approved the AbioCor® Implantable Replacement Heart (AbioCor) for destination therapy via the Humanitarian Use Device (HUD) provision; however, the device is no longer being marketed or in development.
CARMAT TAH
A new fully bioprosthetic TAH contains bioprosthetic blood-contacting surfaces and is intended to be used as an end-stage device with the reduction of thromboembolic and hemorrhagic complications in mind. The bioprosthetic TAH, which is electrohydrolically actuated, is fully implanted in the percardial sac after excision of the native ventricles. To date, as part of the feasibility and safety trial, the device (i.e., CARMAT TAH) has been successfully implanted in four individuals at imminent risk of death from biventricular heart failure, not eligible for heart transplant. The four implanted individuals have ultimately died due to either device failure or organ failure. The lack of back-up options, technical complexity, size, and weight remain unsolved. Further research is required to resolve these technical challenges along with well-designed studies needed to provide further clinical evidence of the safety and efficacy of the bioprosthetic TAH.
HUMANITARIAN DEVICE EXEMPTION (HDE)
In rare instances, certain medical devices intended to be used for humanitarian purposes are evaluated by the FDA through the HDE process. The FDA’s humanitarian use device (HUD) designation permits the use of certain medical devices when there is no comparable device available to treat or diagnose a disease or condition affecting fewer than 4,000 individuals annually. Because clinical investigation demonstrating the device's efficacy is not feasible (given the low prevalence of the disease in the population), an HDE grants manufacturers an exemption to the usual premarket approval process and allows marketing of the device only for the FDA-labeled HDE indication(s).
Under FDA requirements, an HUD may only be used after institutional review board (IRB) approval has been obtained for the use of the device in accordance with the FDA-labeled indication(s) under the HDE.
