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Artificial heart

An artificial heart is a device that replaces the heart. Artificial hearts are typically used to bridge the time to heart transplantation, or to permanently replace the heart in the case that a heart transplant (from a deceased human or, experimentally, from a deceased genetically engineered pig) is impossible. Although other similar inventions preceded it from the late 1940s, the first artificial heart to be successfully implanted in a human was the Jarvik-7 in 1982, designed by a team including Willem Johan Kolff, William DeVries and Robert Jarvik.[1]

Artificial heart
An artificial heart displayed at the London Science Museum
[edit on Wikidata]

An artificial heart is distinct from a ventricular assist device (VAD; for either one or both of the ventricles, the heart's lower chambers), which can be a permanent solution also, or the intra-aortic balloon pump – both devices are designed to support a failing heart. It is also distinct from a cardiopulmonary bypass machine, which is an external device used to provide the functions of both the heart and lungs, used only for a few hours at a time, most commonly during cardiac surgery. It is also distinct from a ventilator, used to support failing lungs, or the extracorporeal membrane oxygenation (ECMO), which is used to support those with both inadequate heart and lung function for up to days or weeks, unlike the bypass machine.

History Edit

Origins Edit

A synthetic replacement for a heart remains a long-sought "holy grail" of modern medicine. The obvious benefit of a functional artificial heart would be to lower the need for heart transplants because the demand for organs always greatly exceeds supply.

Although the heart is conceptually a pump, it embodies subtleties that defy straightforward emulation with synthetic materials and power supplies. Consequences of these issues include severe foreign-body rejection and external batteries that limit mobility. These complications limited the lifespan of early human recipients from hours to days.

Early development Edit

The first artificial heart was made by the Soviet scientist Vladimir Demikhov in 1938. It was implanted in a dog.

On 2 July 1952, 41-year-old Henry Opitek, suffering from shortness of breath, made medical history at Harper University Hospital[2] at Wayne State University in Michigan. The Dodrill-GMR heart machine, considered to be the first operational mechanical heart, was successfully used while performing heart surgery.[3][4] Ongoing research was done on calves at Hershey Medical Center, Animal Research Facility, in Hershey, Pennsylvania, during the 1970s.

Forest Dewey Dodrill, working closely with Matthew Dudley, used the machine in 1952 to bypass Henry Opitek's left ventricle for 50 minutes while he opened the patient's left atrium and worked to repair the mitral valve. In Dodrill's post-operative report, he notes, "To our knowledge, this is the first instance of survival of a patient when a mechanical heart mechanism was used to take over the complete body function of maintaining the blood supply of the body while the heart was open and operated on."[5]

A heart–lung machine was first used in 1953 during a successful open heart surgery. John Heysham Gibbon, the inventor of the machine, performed the operation and developed the heart–lung substitute himself.

Following these advances, scientific interest for the development of a solution for heart disease developed in numerous research groups worldwide.

Early designs of total artificial hearts Edit

In 1949, a precursor to the modern artificial heart pump was built by doctors William Sewell and William Glenn of the Yale School of Medicine using an Erector Set, assorted odds and ends, and dime-store toys. The external pump successfully bypassed the heart of a dog for more than an hour.[6]

Paul Winchell invented an artificial heart with the assistance of Henry Heimlich (the inventor of the Heimlich maneuver) and held the first patent for such a device. The University of Utah developed a similar apparatus around the same time, but when they tried to patent it, Winchell's heart was cited as prior art. The university requested that Winchell donate the heart to the University of Utah, which he did. There is some debate as to how much of Winchell's design Robert Jarvik used in creating Jarvik's artificial heart. Heimlich states, "I saw the heart, I saw the patent and I saw the letters. The basic principle used in Winchell's heart and Jarvik's heart is exactly the same.[7] " Jarvik denies that any of Winchell's design elements were incorporated into the device he fabricated for humans which was successfully implanted into Barney Clark in 1982.

On 12 December 1957, Willem Johan Kolff, the world's most prolific inventor of artificial organs, implanted an artificial heart into a dog at Cleveland Clinic. The dog lived for 90 minutes.

In 1958, Domingo Liotta initiated the studies of TAH replacement at Lyon, France, and in 1959–60 at the National University of Córdoba, Argentina. He presented his work at the meeting of the American Society for Artificial Internal Organs held in Atlantic City in March 1961. At that meeting, Liotta described the implantation of three types of orthotopic (inside the pericardial sac) TAHs in dogs, each of which used a different source of external energy: an implantable electric motor, an implantable rotating pump with an external electric motor, and a pneumatic pump.[8][9]

In 1964, the National Institutes of Health started the Artificial Heart Program, with the goal of putting an artificial heart into a human by the end of the decade.[10] The purpose of the program was to develop an implantable artificial heart, including the power source, to replace a failing heart.[11]

In February 1966, Adrian Kantrowitz rose to international prominence when he performed the world's first permanent implantation of a partial mechanical heart (left ventricular assist device) at Maimonides Medical Center.[12]

In 1967, Kolff left Cleveland Clinic to start the Division of Artificial Organs at the University of Utah and pursue his work on the artificial heart.

  1. In 1973, a calf named Tony survived for 30 days on an early Kolff heart.
  2. In 1975, a bull named Burk survived 90 days on the artificial heart.
  3. In 1976, a calf named Abebe lived for 184 days on the Jarvik 5 artificial heart.
  4. In 1981, a calf named Alfred Lord Tennyson lived for 268 days on the Jarvik 5.

Over the years, more than 200 physicians, engineers, students and faculty developed, tested and improved Kolff's artificial heart. To help manage his many endeavors, Kolff assigned project managers. Each project was named after its manager. Graduate student Robert Jarvik was the project manager for the artificial heart, which was subsequently renamed the Jarvik 7.

In 1981, William DeVries submitted a request to the FDA for permission to implant the Jarvik 7 into a human being. On 1 December 1982, William DeVries implanted the Jarvik 7 artificial heart into Barney Clark, a dentist from Seattle who had severe congestive heart failure. Clark lived for 112 days tethered to an external pneumatic compressor, a device weighing some 400 pounds (180 kg), but during that time he experienced prolonged periods of confusion and a number of instances of bleeding, and asked several times to be allowed to die.[13]

First clinical implantation of a total artificial heart Edit

On 4 April 1969, Domingo Liotta and Denton A. Cooley replaced a dying man's heart with a mechanical heart inside the chest at The Texas Heart Institute in Houston as a bridge for a transplant. The man woke up and began to recover. After 64 hours, the pneumatic-powered artificial heart was removed and replaced by a donor heart. However thirty-two hours after transplantation, the man died of what was later proved to be an acute pulmonary infection, extended to both lungs, caused by fungi, most likely caused by an immunosuppressive drug complication.[14]

The original prototype of Liotta-Cooley artificial heart used in this historic operation is prominently displayed in the Smithsonian Institution's National Museum of American History "Treasures of American History" exhibit in Washington, D.C.[15]

First clinical applications of a permanent pneumatic total artificial heart Edit

The first clinical use of an artificial heart designed for permanent implantation rather than a bridge to transplant occurred in 1982 at the University of Utah. Artificial kidney pioneer Willem Johan Kolff started the Utah artificial organs program in 1967.[16] There, physician-engineer Clifford Kwan-Gett invented two components of an integrated pneumatic artificial heart system: a ventricle with hemispherical diaphragms that did not crush red blood cells (a problem with previous artificial hearts) and an external heart driver that inherently regulated blood flow without needing complex control systems.[17] Independently, Paul Winchell designed and patented a similarly shaped ventricle and donated the patent to the Utah program.[18] Throughout the 1970s and early 1980s, veterinarian Donald Olsen led a series of calf experiments that refined the artificial heart and its surgical care. During that time, as a student at the University of Utah, Robert Jarvik combined several modifications: an ovoid shape to fit inside the human chest, a more blood-compatible polyurethane developed by biomedical engineer Donald Lyman, and a fabrication method by Kwan-Gett that made the inside of the ventricles smooth and seamless to reduce dangerous stroke-causing blood clots.[19] On 1 December 1982, William DeVries implanted the artificial heart into retired dentist Barney Bailey Clark (born 21 January 1921), who survived 112 days[20] with the device, dying on 23 March 1983. Bill Schroeder became the second recipient and lived for a record 620 days.

Contrary to popular belief and erroneous articles in several periodicals, the Jarvik heart was not banned for permanent use. Today, the modern version of the Jarvik 7 is known as the SynCardia temporary Total Artificial Heart. It has been implanted in more than 1,350 people as a bridge to transplantation.

In the mid-1980s, artificial hearts were powered by dishwasher-sized pneumatic power sources whose lineage went back to Alfa Laval milking machines. Moreover, two sizable catheters had to cross the body wall to carry the pneumatic pulses to the implanted heart, greatly increasing the risk of infection. To speed development of a new generation of technologies, the National Heart, Lung, and Blood Institute opened a competition for implantable electrically powered artificial hearts. Three groups received funding: Cleveland Clinic in Cleveland, Ohio; the College of Medicine of Pennsylvania State University (Penn State Hershey Medical Center) in Hershey, Pennsylvania; and AbioMed, Inc. of Danvers, Massachusetts. Despite considerable progress, the Cleveland program was discontinued after the first five years.

First clinical application of an intrathoracic pump Edit

On 19 July 1963, E. Stanley Crawford and Domingo Liotta implanted the first clinical Left Ventricular Assist Device (LVAD) at The Methodist Hospital in Houston, Texas, in a patient who had a cardiac arrest after surgery. The patient survived for four days under mechanical support but did not recover from the complications of the cardiac arrest; finally, the pump was discontinued, and the patient died.

First clinical application of a paracorporeal pump Edit

 
1966 DeBakey ventricular assist device.[21]

On 21 April 1966, Michael DeBakey and Liotta implanted the first clinical LVAD in a paracorporeal position (where the external pump rests at the side of the patient) at The Methodist Hospital in Houston, in a patient experiencing cardiogenic shock after heart surgery. The patient developed neurological and pulmonary complications and died after few days of LVAD mechanical support. In October 1966, DeBakey and Liotta implanted the paracorporeal Liotta-DeBakey LVAD in a new patient who recovered well and was discharged from the hospital after 10 days of mechanical support, thus constituting the first successful use of an LVAD for postcardiotomy shock.

First VAD patient with FDA approved hospital discharge Edit

In 1990 Brian Williams was discharged from the University of Pittsburgh Medical Center (UPMC), becoming the first VAD patient to be discharged with Food and Drug Administration (FDA) approval.[22] The patient was supported in part by bioengineers from the University of Pittsburgh's McGowan Institute.[22][23]

Total artificial hearts Edit

Approved medical devices Edit

SynCardia Edit

SynCardia is a company based in Tucson, Arizona, which currently has two separate models available. It is available in a 70cc and 50cc size. The 70cc model is used for biventricular heart failure in adult men, while the 50cc is for children and women.[24] As good results with the TAH as a bridge to heart transplant accumulated, a trial of the CardioWest TAH (developed from the Jarvik 7 and now marketed as the Syncardia TAH) was initiated in 1993 and completed in 2002.[25] The SynCardia was first approved for use in 2004 by the US Food and Drug Administration.[26]

As of 2014, more than 1,250 patients have received SynCardia artificial hearts.[27][28] The device requires the use of the Companion 2 in-hospital driver, approved by the FDA in 2012, or the Freedom Driver System, approved in 2014, which allows some patients to return home. These drivers are large, heavy, but portable devices that generate air pulses to power the heart.[26][29] The drivers also monitor blood flow for each ventricle.[30]

In 2016, Syncardia filed for bankruptcy protection and was later acquired by the private equity firm Versa Capital Management.[31]

Carmat bioprosthetic heart Edit

 
Carmat's artificial heart.

On 27 October 2008, French professor and leading heart transplant specialist Alain F. Carpentier announced that a fully implantable artificial heart would be ready for clinical trial by 2011 and for alternative transplant in 2013. It was developed and would be manufactured by him, biomedical firm CARMAT SA,[32] and venture capital firm Truffle Capital. The prototype used embedded electronic sensors and was made from chemically treated animal tissues, called "biomaterials", or a "pseudo-skin" of biosynthetic, microporous materials.[33]

According to a press-release by Carmat dated 20 December 2013, the first implantation of its artificial heart in a 75-year-old patient was performed on 18 December 2013 by the Georges Pompidou European Hospital team in Paris (France).[34] The patient died 75 days after the operation.[35]

In Carmat's design, two chambers are each divided by a membrane that holds hydraulic fluid on one side. A motorized pump moves hydraulic fluid in and out of the chambers, and that fluid causes the membrane to move; blood flows through the other side of each membrane. The blood-facing side of the membrane is made of tissue obtained from a sac that surrounds a cow's heart, to make the device more biocompatible. The Carmat device also uses valves made from cow heart tissue and has sensors to detect increased pressure within the device. That information is sent to an internal control system that can adjust the flow rate in response to increased demand, such as when a patient is exercising.[36] This distinguishes it from previous designs that maintain a constant flow rate.[citation needed]

The Carmat device, unlike previous designs, is meant to be used in cases of terminal heart failure, instead of being used as a bridge device while the patient awaits a transplant.[37] At 900 grams it weighs nearly three times the typical heart and is targeted primarily towards obese men. It also requires the patient to carry around an additional Li-Ion battery. The projected lifetime of the artificial heart is around 5 years (230 million beats).[38]

In 2016, trials for the Carmat "fully artificial heart" were banned by the National Agency for Security and Medicine in Europe after short survival rates were confirmed. The ban was lifted in May 2017. At that time, a European report stated that Celyad's C-Cure cell therapy for ischemic heart failure[39] "could only help a subpopulation of Phase III study participants, and Carmat will hope that its artificial heart will be able to treat a higher proportion of heart failure patients".[40]

The Carmat artificial heart was approved for sale in the European Union, receiving a CE marking on December 22, 2020.[41]

Historical prototypes Edit

Total artificial heart pump Edit

The U.S. Army artificial heart pump was a compact, air-powered unit developed by Kenneth Woodward at Harry Diamond Laboratories in the early to mid-1960s.[42][43] The Army's heart pump was partially made of plexiglass, and consisted of two valves, a chamber, and a suction flapper.[42] The pump operated without any moving parts under the principle of fluid amplification – providing a pulsating air pressure source resembling a heartbeat.[43]

POLVAD Edit

Since 1991, the Foundation for Cardiac Surgery Development (FRK) in Zabrze, Poland, has been working on developing an artificial heart. Nowadays,[when?] the Polish system for heart support POLCAS consists of the artificial ventricle POLVAD-MEV and the three controllers POLPDU-401, POLPDU-402 and POLPDU-501. Presented devices are designed to handle only one patient. The control units of the 401 and 402 series may be used only in hospital due to its big size, method of control and type of power supply. The control[44] unit of 501 series is the latest product of FRK. Due to its much smaller size and weight, it is significantly more mobile solution. For this reason, it can be also used during supervised treatment conducted outside the hospital.[citation needed]

Phoenix-7 Edit

In June 1996, a 46-year-old man received a total artificial heart implantation done by Jeng Wei at Cheng-Hsin General Hospital[45] in Taiwan. This technologically advanced pneumatic Phoenix-7 Total Artificial Heart was manufactured by Taiwanese dentist Kelvin K. Cheng, Chinese physician T. M. Kao, and colleagues at the Taiwan TAH Research Center in Tainan, Taiwan. With this experimental artificial heart, the patient's BP was maintained at 90–100/40–55 mmHg and cardiac output at 4.2–5.8 L/min.[46] The patient then received the world's first successful combined heart and kidney transplantation after bridging with a total artificial heart.[47]

Abiomed hearts Edit

The first AbioCor to be surgically implanted in a patient was on 3 July 2001.[48] The AbioCor is made of titanium and plastic with a weight of 0.9 kg (two pounds), and its internal battery can be recharged with a transduction device that sends power through the skin.[48] The internal battery lasts for half an hour, and a wearable external battery pack lasts for four hours.[49] The FDA announced on 5 September 2006, that the AbioCor could be implanted for humanitarian uses after the device had been tested on 15 patients.[50] It is intended for critically ill patients who cannot receive a heart transplant.[50] Some limitations of the current AbioCor are that its size makes it suitable for less than 50% of the female population and only about 50% of the male population, and its useful life is only 1–2 years.[51]

By combining its valved ventricles with the control technology and roller screw developed at Penn State, AbioMed designed a smaller, more stable heart, the AbioCor II. This pump, which should be implantable in most men and 50% of women with a life span of up to five years,[51] had animal trials in 2005, and the company hoped to get FDA approval for human use in 2008.[52] After a great deal of experimentation, Abiomed has abandoned development of total official hearts as of 2015.[53] Abiomed as of 2019 only markets heart pumps,[54] "intended to help pump blood in patients who need short-term support (up to 6 days)",[55] which are not total artificial hearts.

Frazier-Cohn Edit

On 12 March 2011, an experimental artificial heart was implanted in 55-year-old Craig Lewis at The Texas Heart Institute in Houston by O. H. Frazier and William Cohn. The device is a combination of two modified HeartMate II pumps that is currently undergoing bovine trials.[56]

Frazier and Cohn are on the board of the BiVACOR company that develops an artificial heart.[57][58] BiVACOR has been tested as a replacement for a heart in a sheep.[59][60]

So far, only one person has benefited from Frazier and Cohn's artificial heart. Craig Lewis had amyloidosis in 2011 and sought treatment. After obtaining permission from his family, Frazier and Cohn replaced his heart with their device. Lewis survived for another 5 weeks after the operation; he eventually died from liver and kidney failure due to his amyloidosis, after which his family asked that his artificial heart be unplugged.[61]

 
Soft Total Artificial Heart, developed in the functional material laboratory at ETH Zürich

Current prototypes Edit

Soft artificial heart Edit

On 10 July 2017, Nicholas Cohrs and colleagues presented a new concept of a soft total artificial heart in the Journal of Artificial Organs.[62] The heart was developed in the Functionals Materials Laboratory at ETH Zurich.[63] (Cohrs was listed as a doctoral student in a group led by Professor Wendelin Stark at ETH Zurich.)[64]

The soft artificial heart (SAH) is a silicone monoblock fabricated with the help of 3D bioprinting technology. It weighs 390g, has a volume of 679 cm3, and is operated through pressurized air. "Our goal is to develop an artificial heart that is roughly the same size as the patient's own one and which imitates the human heart as closely as possible in form and function", Cohrs said in an interview.[65] The SAH fundamentally moves and works like a natural heart, but the prototype only performed for 3000 beats (about 30 to 50 minutes at an average heart rate)[66] in a hybrid mock circulation machine[citation needed] before the silicone membrane (2.3 mm thick) between the Left Ventricle and the Air Expansion Chamber ruptured.[67]

The working life of a more recent Cohrs prototype (using various polymers instead of silicone)[citation needed] was still limited, according to reports in early 2018, with that model providing a useful life of 1 million heartbeats, roughly ten days in a human body.[68] At the time, Cohrs and his team were experimenting with CAD software and 3D printing, striving to develop a model that would last up to 15 years. "We cannot really predict when we could have a final working heart which fulfills all requirements and is ready for implantation. This usually takes years", said Cohrs.[citation needed]

Others Edit

A centrifugal pump[69][70] or an axial-flow pump[71][72] can be used as an artificial heart, resulting in the patient being alive without a pulse. Other pulse-less artificial heart designs include the HeartMate II from Thoratec, which uses an Archimedes screw; and an experimental artificial heart designed by Bud Frazier and Billy Cohn, using turbines spinning at 8,000 to 12,000 RPM.[73]

A centrifugal artificial heart which alternately pumps the pulmonary circulation and the systemic circulation, causing a pulse, has been described.[74]

Researchers have constructed a heart out of foam. The heart is made out of flexible silicone and works with an external pump to push air and fluids through the heart. It currently cannot be implanted into humans, but it is a promising start for artificial hearts.[75]

Hybrid assistive devices Edit

Patients who have some remaining heart function but who can no longer live normally may be candidates for ventricular assist devices (VAD), which do not replace the human heart but complement it by taking up much of the function.[1]

The first Left Ventricular Assist Device (LVAD) system was created by Domingo Liotta at Baylor College of Medicine in Houston in 1962.[76]

Another VAD, the Kantrowitz CardioVad, designed by Adrian Kantrowitz, boosts the native heart by taking up over 50% of its function.[77] Additionally, the VAD can help patients on the wait list for a heart transplant. In a young person, this device could delay the need for a transplant by 10–15 years, or even allow the heart to recover, in which case the VAD can be removed.[77] The artificial heart is powered by a battery that needs to be changed several times while still working.[citation needed]

The first heart assist device was approved by the FDA in 1994, and two more received approval in 1998.[78] While the original assist devices emulated the pulsating heart, newer versions, such as the Heartmate II,[79] developed by The Texas Heart Institute of Houston, provide continuous flow. These pumps (which may be centrifugal or axial flow) are smaller and potentially more durable and last longer than the current generation of total heart replacement pumps. Another major advantage of a VAD is that the patient keeps the natural heart, which may still function for temporary back-up support if the mechanical pump were to stop. This may provide enough support to keep the patient alive until a solution to the problem is implemented.[citation needed]

In August 2006, an artificial heart was implanted into a 15-year-old girl at the Stollery Children's Hospital in Edmonton, Alberta. It was intended to act as a temporary fixture until a donor heart could be found. Instead, the artificial heart (called a Berlin Heart) allowed for natural processes to occur and her heart healed on its own. After 146 days, the Berlin Heart was removed, and the girl's heart functioned properly on its own.[80] On 16 December 2011 the Berlin Heart gained U.S. FDA approval. The device has since been successfully implanted in several children including a 4-year-old Honduran girl at Children's Hospital Boston.[81]

Several continuous-flow ventricular assist devices have been approved for use in the European Union, and, as of August 2007, were undergoing clinical trials for FDA approval.

In 2012, Craig Lewis, a 55-year-old Texan, presented at the Texas Heart Institute with a severe case of cardiac amyloidosis. He was given an experimental continuous-flow artificial heart transplant which saved his life. Lewis died 5 weeks later of liver failure after slipping into a coma due to the amyloidosis.[73]

In 2012, a study published in the New England Journal of Medicine compared the Berlin Heart to extracorporeal membrane oxygenation (ECMO) and concluded that "a ventricular assist device available in several sizes for use in children as a bridge to heart transplantation [such as the Berlin Heart] was associated with a significantly higher rate of survival as compared with ECMO."[82] The study's primary author, Charles D. Fraser Jr., surgeon in chief at Texas Children's Hospital, explained: "With the Berlin Heart, we have a more effective therapy to offer patients earlier in the management of their heart failure. When we sit with parents, we have real data to offer so they can make an informed decision. This is a giant step forward."[83]

Suffering from end-stage heart failure, former Vice President Dick Cheney underwent a procedure at INOVA Fairfax Hospital, in Fairfax Virginia in July 2010, to have a Heartmate II VAD implanted.[1] In 2012, he received a heart transplant at age 71 after 20 months on a waiting list.

See also Edit

References Edit

General references Edit

  • George B. Griffenhagen and Calvin H. Hughes. The History of the Mechanical Heart. Smithsonian Report for 1955, (Pub. 4241): 339–356, 1956.
  • "Donor saves Detroit pastor living on artificial heart". Fox News. 18 May 2018

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Further reading Edit

  • Mimi Swartz (2018). Ticker: The Quest to Create an Artificial Heart. Crown. ISBN 978-0804138000.

External links Edit

  • Kembrey, Melanie (17 August 2010). . Fairfield City Champion. Archived 6 July 2011.

artificial, heart, this, article, about, mechanical, device, jonathan, coulton, album, artificial, heart, album, artificial, heart, device, that, replaces, heart, typically, used, bridge, time, heart, transplantation, permanently, replace, heart, case, that, h. This article is about the mechanical device For the Jonathan Coulton album see Artificial Heart album An artificial heart is a device that replaces the heart Artificial hearts are typically used to bridge the time to heart transplantation or to permanently replace the heart in the case that a heart transplant from a deceased human or experimentally from a deceased genetically engineered pig is impossible Although other similar inventions preceded it from the late 1940s the first artificial heart to be successfully implanted in a human was the Jarvik 7 in 1982 designed by a team including Willem Johan Kolff William DeVries and Robert Jarvik 1 Artificial heartAn artificial heart displayed at the London Science Museum edit on Wikidata An artificial heart is distinct from a ventricular assist device VAD for either one or both of the ventricles the heart s lower chambers which can be a permanent solution also or the intra aortic balloon pump both devices are designed to support a failing heart It is also distinct from a cardiopulmonary bypass machine which is an external device used to provide the functions of both the heart and lungs used only for a few hours at a time most commonly during cardiac surgery It is also distinct from a ventilator used to support failing lungs or the extracorporeal membrane oxygenation ECMO which is used to support those with both inadequate heart and lung function for up to days or weeks unlike the bypass machine Contents 1 History 1 1 Origins 1 2 Early development 1 3 Early designs of total artificial hearts 1 4 First clinical implantation of a total artificial heart 1 5 First clinical applications of a permanent pneumatic total artificial heart 1 6 First clinical application of an intrathoracic pump 1 7 First clinical application of a paracorporeal pump 1 8 First VAD patient with FDA approved hospital discharge 2 Total artificial hearts 2 1 Approved medical devices 2 1 1 SynCardia 2 1 2 Carmat bioprosthetic heart 2 2 Historical prototypes 2 2 1 Total artificial heart pump 2 2 2 POLVAD 2 2 3 Phoenix 7 2 2 4 Abiomed hearts 2 2 5 Frazier Cohn 2 3 Current prototypes 2 3 1 Soft artificial heart 3 Others 3 1 Hybrid assistive devices 4 See also 5 References 5 1 General references 5 2 Inline citations 6 Further reading 7 External linksHistory EditThis section needs additional citations for verification Please help improve this article by adding citations to reliable sources in this section Unsourced material may be challenged and removed Find sources Artificial heart news newspapers books scholar JSTOR April 2018 Learn how and when to remove this template message Origins Edit A synthetic replacement for a heart remains a long sought holy grail of modern medicine The obvious benefit of a functional artificial heart would be to lower the need for heart transplants because the demand for organs always greatly exceeds supply Although the heart is conceptually a pump it embodies subtleties that defy straightforward emulation with synthetic materials and power supplies Consequences of these issues include severe foreign body rejection and external batteries that limit mobility These complications limited the lifespan of early human recipients from hours to days Early development Edit The first artificial heart was made by the Soviet scientist Vladimir Demikhov in 1938 It was implanted in a dog On 2 July 1952 41 year old Henry Opitek suffering from shortness of breath made medical history at Harper University Hospital 2 at Wayne State University in Michigan The Dodrill GMR heart machine considered to be the first operational mechanical heart was successfully used while performing heart surgery 3 4 Ongoing research was done on calves at Hershey Medical Center Animal Research Facility in Hershey Pennsylvania during the 1970s Forest Dewey Dodrill working closely with Matthew Dudley used the machine in 1952 to bypass Henry Opitek s left ventricle for 50 minutes while he opened the patient s left atrium and worked to repair the mitral valve In Dodrill s post operative report he notes To our knowledge this is the first instance of survival of a patient when a mechanical heart mechanism was used to take over the complete body function of maintaining the blood supply of the body while the heart was open and operated on 5 A heart lung machine was first used in 1953 during a successful open heart surgery John Heysham Gibbon the inventor of the machine performed the operation and developed the heart lung substitute himself Following these advances scientific interest for the development of a solution for heart disease developed in numerous research groups worldwide Early designs of total artificial hearts Edit In 1949 a precursor to the modern artificial heart pump was built by doctors William Sewell and William Glenn of the Yale School of Medicine using an Erector Set assorted odds and ends and dime store toys The external pump successfully bypassed the heart of a dog for more than an hour 6 Paul Winchell invented an artificial heart with the assistance of Henry Heimlich the inventor of the Heimlich maneuver and held the first patent for such a device The University of Utah developed a similar apparatus around the same time but when they tried to patent it Winchell s heart was cited as prior art The university requested that Winchell donate the heart to the University of Utah which he did There is some debate as to how much of Winchell s design Robert Jarvik used in creating Jarvik s artificial heart Heimlich states I saw the heart I saw the patent and I saw the letters The basic principle used in Winchell s heart and Jarvik s heart is exactly the same 7 Jarvik denies that any of Winchell s design elements were incorporated into the device he fabricated for humans which was successfully implanted into Barney Clark in 1982 On 12 December 1957 Willem Johan Kolff the world s most prolific inventor of artificial organs implanted an artificial heart into a dog at Cleveland Clinic The dog lived for 90 minutes In 1958 Domingo Liotta initiated the studies of TAH replacement at Lyon France and in 1959 60 at the National University of Cordoba Argentina He presented his work at the meeting of the American Society for Artificial Internal Organs held in Atlantic City in March 1961 At that meeting Liotta described the implantation of three types of orthotopic inside the pericardial sac TAHs in dogs each of which used a different source of external energy an implantable electric motor an implantable rotating pump with an external electric motor and a pneumatic pump 8 9 In 1964 the National Institutes of Health started the Artificial Heart Program with the goal of putting an artificial heart into a human by the end of the decade 10 The purpose of the program was to develop an implantable artificial heart including the power source to replace a failing heart 11 In February 1966 Adrian Kantrowitz rose to international prominence when he performed the world s first permanent implantation of a partial mechanical heart left ventricular assist device at Maimonides Medical Center 12 In 1967 Kolff left Cleveland Clinic to start the Division of Artificial Organs at the University of Utah and pursue his work on the artificial heart In 1973 a calf named Tony survived for 30 days on an early Kolff heart In 1975 a bull named Burk survived 90 days on the artificial heart In 1976 a calf named Abebe lived for 184 days on the Jarvik 5 artificial heart In 1981 a calf named Alfred Lord Tennyson lived for 268 days on the Jarvik 5 Over the years more than 200 physicians engineers students and faculty developed tested and improved Kolff s artificial heart To help manage his many endeavors Kolff assigned project managers Each project was named after its manager Graduate student Robert Jarvik was the project manager for the artificial heart which was subsequently renamed the Jarvik 7 In 1981 William DeVries submitted a request to the FDA for permission to implant the Jarvik 7 into a human being On 1 December 1982 William DeVries implanted the Jarvik 7 artificial heart into Barney Clark a dentist from Seattle who had severe congestive heart failure Clark lived for 112 days tethered to an external pneumatic compressor a device weighing some 400 pounds 180 kg but during that time he experienced prolonged periods of confusion and a number of instances of bleeding and asked several times to be allowed to die 13 First clinical implantation of a total artificial heart Edit On 4 April 1969 Domingo Liotta and Denton A Cooley replaced a dying man s heart with a mechanical heart inside the chest at The Texas Heart Institute in Houston as a bridge for a transplant The man woke up and began to recover After 64 hours the pneumatic powered artificial heart was removed and replaced by a donor heart However thirty two hours after transplantation the man died of what was later proved to be an acute pulmonary infection extended to both lungs caused by fungi most likely caused by an immunosuppressive drug complication 14 The original prototype of Liotta Cooley artificial heart used in this historic operation is prominently displayed in the Smithsonian Institution s National Museum of American History Treasures of American History exhibit in Washington D C 15 First clinical applications of a permanent pneumatic total artificial heart Edit The first clinical use of an artificial heart designed for permanent implantation rather than a bridge to transplant occurred in 1982 at the University of Utah Artificial kidney pioneer Willem Johan Kolff started the Utah artificial organs program in 1967 16 There physician engineer Clifford Kwan Gett invented two components of an integrated pneumatic artificial heart system a ventricle with hemispherical diaphragms that did not crush red blood cells a problem with previous artificial hearts and an external heart driver that inherently regulated blood flow without needing complex control systems 17 Independently Paul Winchell designed and patented a similarly shaped ventricle and donated the patent to the Utah program 18 Throughout the 1970s and early 1980s veterinarian Donald Olsen led a series of calf experiments that refined the artificial heart and its surgical care During that time as a student at the University of Utah Robert Jarvik combined several modifications an ovoid shape to fit inside the human chest a more blood compatible polyurethane developed by biomedical engineer Donald Lyman and a fabrication method by Kwan Gett that made the inside of the ventricles smooth and seamless to reduce dangerous stroke causing blood clots 19 On 1 December 1982 William DeVries implanted the artificial heart into retired dentist Barney Bailey Clark born 21 January 1921 who survived 112 days 20 with the device dying on 23 March 1983 Bill Schroeder became the second recipient and lived for a record 620 days Contrary to popular belief and erroneous articles in several periodicals the Jarvik heart was not banned for permanent use Today the modern version of the Jarvik 7 is known as the SynCardia temporary Total Artificial Heart It has been implanted in more than 1 350 people as a bridge to transplantation In the mid 1980s artificial hearts were powered by dishwasher sized pneumatic power sources whose lineage went back to Alfa Laval milking machines Moreover two sizable catheters had to cross the body wall to carry the pneumatic pulses to the implanted heart greatly increasing the risk of infection To speed development of a new generation of technologies the National Heart Lung and Blood Institute opened a competition for implantable electrically powered artificial hearts Three groups received funding Cleveland Clinic in Cleveland Ohio the College of Medicine of Pennsylvania State University Penn State Hershey Medical Center in Hershey Pennsylvania and AbioMed Inc of Danvers Massachusetts Despite considerable progress the Cleveland program was discontinued after the first five years First clinical application of an intrathoracic pump Edit On 19 July 1963 E Stanley Crawford and Domingo Liotta implanted the first clinical Left Ventricular Assist Device LVAD at The Methodist Hospital in Houston Texas in a patient who had a cardiac arrest after surgery The patient survived for four days under mechanical support but did not recover from the complications of the cardiac arrest finally the pump was discontinued and the patient died First clinical application of a paracorporeal pump Edit nbsp 1966 DeBakey ventricular assist device 21 On 21 April 1966 Michael DeBakey and Liotta implanted the first clinical LVAD in a paracorporeal position where the external pump rests at the side of the patient at The Methodist Hospital in Houston in a patient experiencing cardiogenic shock after heart surgery The patient developed neurological and pulmonary complications and died after few days of LVAD mechanical support In October 1966 DeBakey and Liotta implanted the paracorporeal Liotta DeBakey LVAD in a new patient who recovered well and was discharged from the hospital after 10 days of mechanical support thus constituting the first successful use of an LVAD for postcardiotomy shock First VAD patient with FDA approved hospital discharge Edit In 1990 Brian Williams was discharged from the University of Pittsburgh Medical Center UPMC becoming the first VAD patient to be discharged with Food and Drug Administration FDA approval 22 The patient was supported in part by bioengineers from the University of Pittsburgh s McGowan Institute 22 23 Total artificial hearts EditApproved medical devices Edit SynCardia Edit SynCardia is a company based in Tucson Arizona which currently has two separate models available It is available in a 70cc and 50cc size The 70cc model is used for biventricular heart failure in adult men while the 50cc is for children and women 24 As good results with the TAH as a bridge to heart transplant accumulated a trial of the CardioWest TAH developed from the Jarvik 7 and now marketed as the Syncardia TAH was initiated in 1993 and completed in 2002 25 The SynCardia was first approved for use in 2004 by the US Food and Drug Administration 26 As of 2014 more than 1 250 patients have received SynCardia artificial hearts 27 28 The device requires the use of the Companion 2 in hospital driver approved by the FDA in 2012 or the Freedom Driver System approved in 2014 which allows some patients to return home These drivers are large heavy but portable devices that generate air pulses to power the heart 26 29 The drivers also monitor blood flow for each ventricle 30 In 2016 Syncardia filed for bankruptcy protection and was later acquired by the private equity firm Versa Capital Management 31 Carmat bioprosthetic heart Edit nbsp Carmat s artificial heart On 27 October 2008 French professor and leading heart transplant specialist Alain F Carpentier announced that a fully implantable artificial heart would be ready for clinical trial by 2011 and for alternative transplant in 2013 It was developed and would be manufactured by him biomedical firm CARMAT SA 32 and venture capital firm Truffle Capital The prototype used embedded electronic sensors and was made from chemically treated animal tissues called biomaterials or a pseudo skin of biosynthetic microporous materials 33 According to a press release by Carmat dated 20 December 2013 the first implantation of its artificial heart in a 75 year old patient was performed on 18 December 2013 by the Georges Pompidou European Hospital team in Paris France 34 The patient died 75 days after the operation 35 In Carmat s design two chambers are each divided by a membrane that holds hydraulic fluid on one side A motorized pump moves hydraulic fluid in and out of the chambers and that fluid causes the membrane to move blood flows through the other side of each membrane The blood facing side of the membrane is made of tissue obtained from a sac that surrounds a cow s heart to make the device more biocompatible The Carmat device also uses valves made from cow heart tissue and has sensors to detect increased pressure within the device That information is sent to an internal control system that can adjust the flow rate in response to increased demand such as when a patient is exercising 36 This distinguishes it from previous designs that maintain a constant flow rate citation needed The Carmat device unlike previous designs is meant to be used in cases of terminal heart failure instead of being used as a bridge device while the patient awaits a transplant 37 At 900 grams it weighs nearly three times the typical heart and is targeted primarily towards obese men It also requires the patient to carry around an additional Li Ion battery The projected lifetime of the artificial heart is around 5 years 230 million beats 38 In 2016 trials for the Carmat fully artificial heart were banned by the National Agency for Security and Medicine in Europe after short survival rates were confirmed The ban was lifted in May 2017 At that time a European report stated that Celyad s C Cure cell therapy for ischemic heart failure 39 could only help a subpopulation of Phase III study participants and Carmat will hope that its artificial heart will be able to treat a higher proportion of heart failure patients 40 The Carmat artificial heart was approved for sale in the European Union receiving a CE marking on December 22 2020 41 Historical prototypes Edit Total artificial heart pump Edit The U S Army artificial heart pump was a compact air powered unit developed by Kenneth Woodward at Harry Diamond Laboratories in the early to mid 1960s 42 43 The Army s heart pump was partially made of plexiglass and consisted of two valves a chamber and a suction flapper 42 The pump operated without any moving parts under the principle of fluid amplification providing a pulsating air pressure source resembling a heartbeat 43 POLVAD Edit Since 1991 the Foundation for Cardiac Surgery Development FRK in Zabrze Poland has been working on developing an artificial heart Nowadays when the Polish system for heart support POLCAS consists of the artificial ventricle POLVAD MEV and the three controllers POLPDU 401 POLPDU 402 and POLPDU 501 Presented devices are designed to handle only one patient The control units of the 401 and 402 series may be used only in hospital due to its big size method of control and type of power supply The control 44 unit of 501 series is the latest product of FRK Due to its much smaller size and weight it is significantly more mobile solution For this reason it can be also used during supervised treatment conducted outside the hospital citation needed Phoenix 7 Edit In June 1996 a 46 year old man received a total artificial heart implantation done by Jeng Wei at Cheng Hsin General Hospital 45 in Taiwan This technologically advanced pneumatic Phoenix 7 Total Artificial Heart was manufactured by Taiwanese dentist Kelvin K Cheng Chinese physician T M Kao and colleagues at the Taiwan TAH Research Center in Tainan Taiwan With this experimental artificial heart the patient s BP was maintained at 90 100 40 55 mmHg and cardiac output at 4 2 5 8 L min 46 The patient then received the world s first successful combined heart and kidney transplantation after bridging with a total artificial heart 47 Abiomed hearts Edit The first AbioCor to be surgically implanted in a patient was on 3 July 2001 48 The AbioCor is made of titanium and plastic with a weight of 0 9 kg two pounds and its internal battery can be recharged with a transduction device that sends power through the skin 48 The internal battery lasts for half an hour and a wearable external battery pack lasts for four hours 49 The FDA announced on 5 September 2006 that the AbioCor could be implanted for humanitarian uses after the device had been tested on 15 patients 50 It is intended for critically ill patients who cannot receive a heart transplant 50 Some limitations of the current AbioCor are that its size makes it suitable for less than 50 of the female population and only about 50 of the male population and its useful life is only 1 2 years 51 By combining its valved ventricles with the control technology and roller screw developed at Penn State AbioMed designed a smaller more stable heart the AbioCor II This pump which should be implantable in most men and 50 of women with a life span of up to five years 51 had animal trials in 2005 and the company hoped to get FDA approval for human use in 2008 52 After a great deal of experimentation Abiomed has abandoned development of total official hearts as of 2015 53 Abiomed as of 2019 only markets heart pumps 54 intended to help pump blood in patients who need short term support up to 6 days 55 which are not total artificial hearts Frazier Cohn Edit On 12 March 2011 an experimental artificial heart was implanted in 55 year old Craig Lewis at The Texas Heart Institute in Houston by O H Frazier and William Cohn The device is a combination of two modified HeartMate II pumps that is currently undergoing bovine trials 56 Frazier and Cohn are on the board of the BiVACOR company that develops an artificial heart 57 58 BiVACOR has been tested as a replacement for a heart in a sheep 59 60 So far only one person has benefited from Frazier and Cohn s artificial heart Craig Lewis had amyloidosis in 2011 and sought treatment After obtaining permission from his family Frazier and Cohn replaced his heart with their device Lewis survived for another 5 weeks after the operation he eventually died from liver and kidney failure due to his amyloidosis after which his family asked that his artificial heart be unplugged 61 nbsp Soft Total Artificial Heart developed in the functional material laboratory at ETH ZurichCurrent prototypes Edit Soft artificial heart Edit On 10 July 2017 Nicholas Cohrs and colleagues presented a new concept of a soft total artificial heart in the Journal of Artificial Organs 62 The heart was developed in the Functionals Materials Laboratory at ETH Zurich 63 Cohrs was listed as a doctoral student in a group led by Professor Wendelin Stark at ETH Zurich 64 The soft artificial heart SAH is a silicone monoblock fabricated with the help of 3D bioprinting technology It weighs 390g has a volume of 679 cm3 and is operated through pressurized air Our goal is to develop an artificial heart that is roughly the same size as the patient s own one and which imitates the human heart as closely as possible in form and function Cohrs said in an interview 65 The SAH fundamentally moves and works like a natural heart but the prototype only performed for 3000 beats about 30 to 50 minutes at an average heart rate 66 in a hybrid mock circulation machine citation needed before the silicone membrane 2 3 mm thick between the Left Ventricle and the Air Expansion Chamber ruptured 67 The working life of a more recent Cohrs prototype using various polymers instead of silicone citation needed was still limited according to reports in early 2018 with that model providing a useful life of 1 million heartbeats roughly ten days in a human body 68 At the time Cohrs and his team were experimenting with CAD software and 3D printing striving to develop a model that would last up to 15 years We cannot really predict when we could have a final working heart which fulfills all requirements and is ready for implantation This usually takes years said Cohrs citation needed Others EditA centrifugal pump 69 70 or an axial flow pump 71 72 can be used as an artificial heart resulting in the patient being alive without a pulse Other pulse less artificial heart designs include the HeartMate II from Thoratec which uses an Archimedes screw and an experimental artificial heart designed by Bud Frazier and Billy Cohn using turbines spinning at 8 000 to 12 000 RPM 73 A centrifugal artificial heart which alternately pumps the pulmonary circulation and the systemic circulation causing a pulse has been described 74 Researchers have constructed a heart out of foam The heart is made out of flexible silicone and works with an external pump to push air and fluids through the heart It currently cannot be implanted into humans but it is a promising start for artificial hearts 75 Hybrid assistive devices Edit Main article Ventricular assist device Patients who have some remaining heart function but who can no longer live normally may be candidates for ventricular assist devices VAD which do not replace the human heart but complement it by taking up much of the function 1 The first Left Ventricular Assist Device LVAD system was created by Domingo Liotta at Baylor College of Medicine in Houston in 1962 76 Another VAD the Kantrowitz CardioVad designed by Adrian Kantrowitz boosts the native heart by taking up over 50 of its function 77 Additionally the VAD can help patients on the wait list for a heart transplant In a young person this device could delay the need for a transplant by 10 15 years or even allow the heart to recover in which case the VAD can be removed 77 The artificial heart is powered by a battery that needs to be changed several times while still working citation needed The first heart assist device was approved by the FDA in 1994 and two more received approval in 1998 78 While the original assist devices emulated the pulsating heart newer versions such as the Heartmate II 79 developed by The Texas Heart Institute of Houston provide continuous flow These pumps which may be centrifugal or axial flow are smaller and potentially more durable and last longer than the current generation of total heart replacement pumps Another major advantage of a VAD is that the patient keeps the natural heart which may still function for temporary back up support if the mechanical pump were to stop This may provide enough support to keep the patient alive until a solution to the problem is implemented citation needed In August 2006 an artificial heart was implanted into a 15 year old girl at the Stollery Children s Hospital in Edmonton Alberta It was intended to act as a temporary fixture until a donor heart could be found Instead the artificial heart called a Berlin Heart allowed for natural processes to occur and her heart healed on its own After 146 days the Berlin Heart was removed and the girl s heart functioned properly on its own 80 On 16 December 2011 the Berlin Heart gained U S FDA approval The device has since been successfully implanted in several children including a 4 year old Honduran girl at Children s Hospital Boston 81 Several continuous flow ventricular assist devices have been approved for use in the European Union and as of August 2007 were undergoing clinical trials for FDA approval In 2012 Craig Lewis a 55 year old Texan presented at the Texas Heart Institute with a severe case of cardiac amyloidosis He was given an experimental continuous flow artificial heart transplant which saved his life Lewis died 5 weeks later of liver failure after slipping into a coma due to the amyloidosis 73 In 2012 a study published in the New England Journal of Medicine compared the Berlin Heart to extracorporeal membrane oxygenation ECMO and concluded that a ventricular assist device available in several sizes for use in children as a bridge to heart transplantation such as the Berlin Heart was associated with a significantly higher rate of survival as compared with ECMO 82 The study s primary author Charles D Fraser Jr surgeon in chief at Texas Children s Hospital explained With the Berlin Heart we have a more effective therapy to offer patients earlier in the management of their heart failure When we sit with parents we have real data to offer so they can make an informed decision This is a giant step forward 83 Suffering from end stage heart failure former Vice President Dick Cheney underwent a procedure at INOVA Fairfax Hospital in Fairfax Virginia in July 2010 to have a Heartmate II VAD implanted 1 In 2012 he received a heart transplant at age 71 after 20 months on a waiting list See also EditOrgan culture Artificial heart valve Artificial cardiac pacemakerReferences EditGeneral references Edit George B Griffenhagen and Calvin H Hughes The History of the Mechanical Heart Smithsonian Report for 1955 Pub 4241 339 356 1956 Donor saves Detroit pastor living on artificial heart Fox News 18 May 2018Inline citations Edit a b c Levy Adam 12 January 2021 The heart of invention Knowable Magazine Annual Reviews doi 10 1146 knowable 011221 1 Retrieved 25 March 2022 Harper University Hospital www harperhospital org Archived from the original on 20 August 2007 Retrieved 11 January 2022 The Mechanical Heart celebrates 50 lifesaving years American Heart Association 9 February 2008 Archived from the original on 21 November 2010 Retrieved 8 March 2013 and Mechanical Heart Celebrates 50 Lifesaving Years Archived from the original on 19 August 2016 Retrieved 3 June 2015 50th Anniversary of First Open Heart 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2011 Dan Baum No Pulse How Doctors Reinvented The Human Heart Archived 2012 11 04 at the Wayback Machine 2012 02 29 a b Baum Dan 29 February 2012 No Pulse How Doctors Reinvented The Human Heart Popular Science Retrieved 16 February 2021 Imachi K Chinzei T Abe Y Mabuchi K Imanishi K Yonezawa T Kouno A Ono T Atsumi K Isoyama T 1991 A new pulsatile total artificial heart using a single centrifugal pump ASAIO Trans 37 3 M242 3 PMID 1751129 New Artificial Heart is Made of Foam Popular Science 1 October 2015 Archived from the original on 5 December 2015 Prolonged Assisted circulation after cardiac or aortic surgery Prolonged partial left ventricular bypass by means of intracorporeal circulation This paper was finalist in The Young Investigators Award Contest of the American College of Cardiology Denver May 1962 Am J Cardiol 1963 12 399 404 a b Mitka Mike 2001 Midwest Trials of Heart Assist Device Journal of the American Medical Association 286 21 2661 doi 10 1001 jama 286 21 2661 PMID 11730426 FDA Approves Two Portable Heart Assist Devices Archived 2007 06 14 at the Wayback Machine at FDA gov An Artificial Heart That Doesn t Beat at TechnologyReview com Berlin Heart Archived from the original on 16 October 2007 Retrieved 29 August 2007 a href Template Cite web html title Template Cite web cite web a CS1 maint bot original URL status unknown link 28 August 2007 Capital Health Edmonton archived from Berlin Heart Archived from the original on 27 September 2007 Retrieved 29 August 2007 the original on 2007 10 01 Newly approved Berlin Heart helps patients waiting for a transplant Vector 30 December 2011 Fraser Charles D Jaquiss Robert D B Rosenthal David N Humpl Tilman Canter Charles E Blackstone Eugene H Naftel David C Ichord Rebecca N Bomgaars Lisa Tweddell James S Massicotte M Patricia Turrentine Mark W Cohen Gordon A Devaney Eric J Pearce F Bennett Carberry Kathleen E Kroslowitz Robert Almond Christopher S 2012 Prospective Trial of a Pediatric Ventricular Assist Device New England Journal of Medicine 367 6 532 541 doi 10 1056 nejmoa1014164 PMID 22873533 News Texas Children s Hospital Archived from the original on 25 April 2013 Further reading EditMimi Swartz 2018 Ticker The Quest to Create an Artificial Heart Crown ISBN 978 0804138000 External links EditKembrey Melanie 17 August 2010 Artificial heart a medical marvel Fairfield City Champion Archived 6 July 2011 Retrieved from https en wikipedia org w index php title Artificial heart amp oldid 1171079869, wikipedia, wiki, book, books, library,

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