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Artificial heart

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This article is about the mechanical device. For the Jonathan Coulton album, see Artificial Heart (album).
File:The SynCardia temporary Total Artificial Heart with pink heart background.jpg
The SynCardia temporary Total Artificial Heart
An artificial heart displayed at the London Science Museum

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 case heart transplantation is impossible. Although other similar inventions preceded it going back to 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 and Robert Jarvik.

An artificial heart is distinct from a ventricular assist device 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 and are used only for a few hours at a time, most commonly during cardiac surgery.

History

Origins

A synthetic replacement for the heart remains one of the long-sought "holy grails" 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 to hours or days.

Early development

The first artificial heart was made by the Soviet scientist Vladimir Demikhov in 1937. It was transplanted to a dog.

On July 3, 1952, 41-year-old Henry Opitek, suffering from shortness of breath, made medical history at Harper University Hospital 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.[1][2]

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."[3]

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

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.[4]

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.[5]" 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 December 12, 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.[6][7]

In 1964, the National Institutes of Health started the Artificial Heart Program, with the goal of putting a man-made heart into a human by the end of the decade.[8] The purpose of the program was to develop an implantable artificial heart, including the power source, to replace a failing heart.[9]

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.[10]

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 December 2, 1982, Kolff implanted the Jarvik 7 artificial heart into Barney Clark, a dentist from Seattle who was suffering from 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 suffered prolonged periods of confusion and a number of instances of bleeding, and asked several times to be allowed to die.[11]

First clinical implantation of a total artificial heart

On April 4, 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.[12]

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.[13]

First clinical applications of a permanent pneumatic total artificial heart

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.[14] 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.[15] Independently, Paul Winchell designed and patented a similarly shaped ventricle and donated the patent to the Utah program.[16] 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.[17] On December 2, 1982, William DeVries implanted the artificial heart into retired dentist Barney Bailey Clark (born January 21, 1921), who survived 112 days with the device, dying on March 23, 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.

Polymeric trileaflet valves ensure unidirectional blood flow with a low pressure gradient and good longevity. State-of-the-art transcutaneous energy transfer eliminates the need for electric wires crossing the chest wall.

First clinical application of an intrathoracic pump

On July 19, 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

1966 DeBakey ventricular assist device.[18]

On April 21, 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

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.[19] The patient was supported in part by bioengineers from the University of Pittsburgh's McGowan Institute.[19][20]

Total artificial heart prototypes

POLVAD

Since 1991, the Foundation for Cardiac Surgery Development (FRK) in Zabrze has been working on developing an artificial heart. Nowadays, 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[21] 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.

Phoenix-7

In June 1996, a 46-year-old man received a total artificial heart implantation done by Jeng Wei at Cheng-Hsin General Hospital[22] in the Republic of China (Taiwan). This technologically advanced pneumatic Phoenix-7 Total Artificial Heart was manufactured by a Taiwanese dentist Kelvin K. Cheng, a Chinese physician T. M. Kao and colleagues at the Taiwan TAH Research Center in Tainan, Republic of China (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.[23] The patient then received the world's first successful combined heart and kidney transplantation after bridging with a total artificial heart.[24]

Abiomed AbioCor

The first AbioCor to be surgically implanted in a patient was on July 3, 2001. [25] The AbioCor is made of titanium and plastic with a weight of two pounds, and its internal battery can be recharged with a transduction device that sends power through the skin.[25] The internal battery lasts for a half-hour, and a wearable external battery pack lasts for four hours.[26] The FDA announced on September 5, 2006, that the AbioCor could be implanted for humanitarian uses after the device had been tested on 15 patients.[27] It is intended for critically ill patients who cannot receive a heart transplant.[27] Some limitations of the current AbioCor are that its size makes it suitable for only about 50% of the male population, and its useful life is only 1–2 years.[28]

SynCardia

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 70 cc is used for biventricular heart failure in adult men, while the 50cc is for children and women.[29] As good results with the TAH as a bridge to heart transplant accumulated, a trial of the CardioWest TAH (developed from the Jarvik 70 and now marketed as the Syncardia TAH) was initiated in 1993 and completed in 2002.[30] As of 2014, more than 1,250 patients have received SynCardia artificial hearts.[31][32][31] The device requires the use of the Companion 2 hospital driver or the Freedom portable driver to power the heart with pulses of air. The drivers also monitor blood flow for each ventricle.[33]

MagScrew

Another U.S. team has a prototype called the 2005 MagScrew Total Artificial Heart. Teams in Japan and South Korea are also racing to produce similar devices.[34][35][36][37]

Abiomed AbioCor II

By combining its valved ventricles with the control technology and roller screw developed at Penn State, AbioMed has 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,[28] had animal trials in 2005, and the company hoped to get FDA approval for human use in 2008.[38]

Carmat bioprosthetic heart

On October 27, 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,[39] 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.[40]

According to a press-release by Carmat dated December 20, 2013, the first implantation of its artificial heart in a 75-year-old patient was performed on December 18, 2013 by the Georges Pompidou European Hospital team in Paris (France).[41] The patient died 75 days after the operation.[42]

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.[43] This distinguishes it from previous designs that maintain a constant flow rate.

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.[44] 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).[45]

Frazier-Cohn

On 12 March 2011, an experimental artificial heart was implanted in 55-year-old Craig Lewis at The Texas Heart Institute in Houston by Drs. O. H. Frazier and William Cohn. The device is a combination of two modified HeartMate II pumps that is currently undergoing bovine trials.[46]

Frazier and Cohn are on the board of the BiVACOR company that develops an artificial heart.[47][48] BiVACOR has been tested as a replacement for a heart in a sheep.[49][50]

So far, only one person has benefited from Frazier and Cohn's artificial heart. Craig Lewis was suffering from amyloidosis in 2011 when his heart gave out and doctors pronounced that he had only 12 to 24 hours to live. 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 succumbed to liver and kidney failure due to his amyloidosis, after which his family asked that his artificial heart be unplugged.[51]

Others

A centrifugal pump[52][53] or an axial-flow pump[54][55] can be used as an artificial heart, resulting in the patient being alive without a pulse.

A centrifugal artificial heart which alternately pumps the pulmonary circulation and the systemic circulation, causing a pulse has been described.[56]

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.[57]

Hybrid assistive devices

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.

The first Left Ventricular Assist Device (LVAD) system was created by Domingo Liotta at Baylor College of Medicine in Houston in 1962.[58]

Another VAD, the Kantrowitz CardioVad, designed by Adrian Kantrowitz boosts the native heart by taking up over 50% of its function.[59] 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.[59] The artificial heart is powered by a battery that needs to be changed several times while still working.

The first heart assist device was approved by the FDA in 1994, and two more received approval in 1998.[60] While the original assist devices emulated the pulsating heart, newer versions, such as the Heartmate II,[61] 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.

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 was able to function properly on its own.[62] On December 16, 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.[63]

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, 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."[64] 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." [65]

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

See also

References

  1. ^ American Heart Association. The Mechanical Heart celebrates 50 lifesaving years. 22 10 2002. Original link: <http://www.americanheart.org/presenter.jhtml;jsessionid=EFNP3NSFUBXLICQFCXQCDSQ?identifier=3005888>(9 Feb 2008). Still available at [1] and [2].
  2. ^ "50th Anniversary of First Open Heart Surgery - Newsroom".
  3. ^ Stephenson Larry W; et al. (2002). "The Michigan Heart: The World's First Successful Open Heart Operation?". Journal of Cardiac Surgery. 17 (3): 238–246. doi:10.1111/j.1540-8191.2002.tb01209.x. PMID 12489911.
  4. ^ Lavietes, Stuart. William Glenn, 88, Surgeon Who Invented Heart Procedure, The New York Times, March 17, 2003. Accessed May 21, 2009.
  5. ^ Jarvik-7 schematic
  6. ^ "Artificial Heart in the chest: Preliminary report". Trans. Amer. Soc. Inter. Organs. 7: 318. 1961.
  7. ^ "Ablation experimentale et replacement du coeur par un coer artificial intra-thoracique". Lyon Cirurgical. 57: 704. 1961.
  8. ^ Sandeep Jauhar: The Artificial Heart. New England Journal of Medicine (2004): 542–544.
  9. ^ Hwang, Ned H. C.; Woo, Savio L.-Y. (31 December 2003). "Frontiers in Biomedical Engineering: Proceedings of the World Congress for Chinese Biomedical Engineers". Springer Science & Business Media – via Google Books.
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  13. ^ "Treasures of American History", National Museum of American History
  14. ^ Spare Parts: Organ Replacement in American Society. Renee C. Fox and Judith P. Swazey. New York: Oxford University Press; 1992, pp. 102–104
  15. ^ Kwan-Gett CS, Van Kampen KR, Kawai J, Eastwood N, Kolff WJ (Dec 1971). "Results of total artificial heart implantation in calves". Journal of Thoracic and Cardiovascular Surgery. 62 (6): 880–889.
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  20. ^ "Pittsburgh's 25th Anniversary of First VAD Patient to Be Discharged from a Hospital - Regenerative Medicine at the McGowan Institute".
  21. ^ Fajdek, Bartlomiej; Janiszowski, Krzysztof. "Automatic control system for ventricular assist device". IEEE. doi:10.1109/MMAR.2014.6957472.
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  23. ^ http://www.worldscientific.com/doi/pdf/10.4015/S1016237201000170
  24. ^ Wei J.; Cheng K. K.; Tung D. Y.; Chang C. Y.; Wan W. M.; Chuang Y. C. (1998). "Successful Use of Phoenix-7 Total Artificial Heart". Transplantation Proceedings. 30: 3403–4. doi:10.1016/s0041-1345(98)01078-1.
  25. ^ a b "Patient gets first totally implanted artificial heart". CNN.com. 2001-07-03. Archived from the original on 7 June 2008. Retrieved 2008-07-13. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  26. ^ "AbioCor FAQs". AbioMed. Archived from the original on 3 July 2008. Retrieved 2008-07-13. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  27. ^ a b "FDA Approves First Totally Implanted Permanent Artificial Heart for Humanitarian Uses". FDA.gov. 2006-09-05. Retrieved 2008-07-13.
  28. ^ a b "Will We Merge With Machines?". popsci.com. 2005-08-01. Archived from the original on 19 July 2008. Retrieved 2008-07-13. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  29. ^ "Two Sizes Intended to Treat Most Patients". SynCardia. November 16, 2015.
  30. ^ Copeland JG, Smith RG, Arabia FA, et al. Cardiac replacement with a total artificial heart as a bridge to transplantation. N Engl J Med 2004;351:859-67
  31. ^ a b "New Record of 161 SynCardia Total Artificial Heart Implants Set In 2013". SynCardia. 2014-01-07. Retrieved 2016-06-11.
  32. ^ Torregrossa G, Morshuis M, Varghese R, et al. Results with SynCardia total artificial heart beyond 1 year. ASAIO J 2014;60:626-34. One patient had the artificial heart for 1,374 days, that is, nearly four years.
  33. ^ SynCardia drivers
  34. ^ MagScrew overview
  35. ^ Helical Flow Total Artificial Heart
  36. ^ HFTAH
  37. ^ South Korean TAH
  38. ^ "14th Artificial Heart Patient Dies: A Newsmaker Interview With Robert Kung, PhD". medscape.com. 2004-11-11. Retrieved 2008-07-13.
  39. ^ atorsoli, Albertina Torsoli. "A Synthetic Heart That Keeps on Ticking".
  40. ^ "The Carmat Heart,- The technology behind the prosthesis". Archived from the original on 2013-06-29. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  41. ^ "First-in-man implantation of CARMAT's bioprosthetic artificial heart".
  42. ^ "First patient fitted with Carmat artificial heart dies". Reuters. March 3, 2014.
  43. ^ Rojahn, Susan Young. "Biology and Machine Come Together in a New Artificial Heart".
  44. ^ "Carmat artificial heart patient in good condition: hospital". Reuters. December 30, 2013.
  45. ^ Polska, Wirtualna. "Pierwsze wszczepione na stałe sztuczne serce bije już w ludzkiej piersi - TechTrendy.pl".
  46. ^ Berger, Eric. "New artificial heart 'a leap forward'". Houston Chronicle. Retrieved 23 March 2011. {{cite web}}: Italic or bold markup not allowed in: |publisher= (help)
  47. ^ "Donor brings inventor of artificial heart closer to Houston". Houston Chronicle. 14 Jan 2013.
  48. ^ "Living without a pulse: Engineering a better artificial heart". CNN. 4 Dec 2013.
  49. ^ "BiVACOR beatless artificial heart appeal hopes to raise $5 million". Courier Mail. 7 March 2015.
  50. ^ "Bionic heart breakthrough: Scientists transplant device into sheep, hope for clinical trials". ABC News. Australian Broadcasting Corporation. 7 March 2015.
  51. ^ "Walking Dead – The First Human Able to Survive Without a Heart OR a Pulse". Bam Marguera. Retrieved 4 April 2015.
  52. ^ Black, Rosemary (January 5, 2011). "Former vice president Dick Cheney now has no pulse". Daily News. New York.
  53. ^ "Pulseless Pumps & Artificial Hearts".
  54. ^ European-Hospital. "The pulseless life on healthcare in europe".
  55. ^ Dan Baum: No Pulse: How Doctors Reinvented The Human Heart. 2012-02-29.
  56. ^ '#A new pulsatile total artificial heart using a single centrifugal pump., K. Imachi, T. Chinzei, Y. Abe, K. Mabuchi, K. Imanishi, T. Yonezawa, A. Kouno, T. Ono, K. Atsumi, T. Isoyama, et al.. Institute of Medical Electronics, Faculty of Medicine, University of Tokyo, Japan.
  57. ^ "New Artificial Heart is Made of Foam". Popular Science. 1 October 2015.
  58. ^ 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
  59. ^ a b Mitka, Mike. "Midwest Trials of Heart-Assist Device." Journal of the American Medical Association 286.21 (2001): 2661.
  60. ^ FDA APPROVES TWO PORTABLE HEART-ASSIST DEVICES at FDA.gov
  61. ^ An Artificial Heart That Doesn't Beat at TechnologyReview.com
  62. ^ Capital Health: One year later: Berlin Heart bridges patient back to health (August 28, 2007), Capital Health, Edmonton (archived from "Archived copy". Archived from the original on 2007-09-27. Retrieved 2007-08-29. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link) the original) on 2007-10-01.
  63. ^ "Newly approved Berlin Heart helps patients waiting for a transplant - Vector". 30 December 2011.
  64. ^ 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. "Prospective Trial of a Pediatric Ventricular Assist Device". 367 (6): 532–541. doi:10.1056/nejmoa1014164. {{cite journal}}: Cite journal requires |journal= (help)
  65. ^ "News - Texas Children's Hospital".
  • George B. Griffenhagen and Calvin H. Hughes. The History of the Mechanical Heart. Smithsonian Report for 1955, (Pub. 4241): 339–356, 1956.
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