by This article is excerpted from Sian E. Harding’s book “The Exquisite Machine: The New Science of the Heart.” It first appeared on The MIT Press Reader.
Nothing represents the perfect engineering of the heart or our own failed attempts to imitate it. The history of the artificial heart is punctuated with great innovation and constant clinical failure. In 1962, John F. Kennedy challenged the scientific community to land a man on the moon and return him safely to Earth by the end of the decade. In 1964, cardiovascular surgeon Michael DeBakey convinced President Lyndon B. Johnson to fund a program to develop the first functional, self-contained artificial heart, launching a race to successfully make one before the moon landing. In 1969 both goals were apparently achieved, with the Texas Heart Institute implanting the first complete artificial heart just three months before the launch of Apollo 11. However, while the Space Shuttle, Mars Rover, and International Space Station, and (despite a long lull) the newest aims to develop a lunar base to take us to Mars, a completely reliable off-the-shelf artificial core that is just getting rid of it.
At the outset, the artificial heart was intended to be a lifelong replacement for the failing organ. This was a high bar to achieve, since the first design had an external compressor with an air line through the skin into the patient’s body. Compressed air inflates and deflates Dacron pouches or sacs, which collapse and expand to displace blood from the surrounding sac. Although having the compressor outside the body was useful, as the mechanical parts (which were more susceptible to wear) could be easily replaced, it would allow for a bulky piece of equipment to be wheeled along. the patient. It was hard to see how a patient could be given this and expect them to have a normal life for many years.
However, the history of the artificial heart is also intertwined with the history of heart transplantation. This was only a hopeful dream in the early 1960s, but by 1967 cardiac surgeon Christian Baarnard in Capetown had performed the first successful transplant. Now, the purpose of these first artificial hearts has changed. They didn’t need to be fit for life; their objective was to keep the patient alive until a transplant donor could be found. As with many highly experimental therapies, the first case was performed on a patient whose options were not available. A 47-year-old man was being operated on to repair a giant aneurysm of the left ventricle that had thinned and swollen the wall of the heart. He was supported by a heart-lung machine, which bypassed the heart and kept blood flowing through the body. However, he could not be removed from the machine at the end of the operation because his heart was too weak. He desperately needed a transplant. Denton Cooley, DeBakey’s associate, offered him the new experimental fully artificial heart and he accepted it. The patient was kept stable with the new device for 64 hours until a matching donor heart was found and then transplanted.
Only around 200 transplants are carried out in the UK each year despite more than 750,000 having heart failure, and similar figures are seen around the world.
This initially seemed like a victory for the total artificial heart, but tragically the patient died 32 hours later from sepsis. Not only that, but the device damaged both the blood and the kidneys, and the walls of the expandable sacs were coated with blood clots. This led to a series of problems that would hinder the scientists and engineers who were struggling with this procedure. Infections and sepsis are a constant challenge for any device that contains a wire that must permanently cross the skin. Devices that move the blood will change its composition and the foreign surfaces will cause the blood to clot, resulting in strokes and blood breakdown. The first Jarvik heart, one of the next iterations, was implanted in five patients and one survived for 620 days. But two of the patients had severe strokes, and all eventually died of sepsis or blood problems.
Heart transplants also got off to a rough start, with Baarnard’s first patient dying after 18 days. The first patient in the UK, who was transplanted by cardiothoracic surgeon Donald Ross at London’s National Heart Hospital, lived just 45 days, and the overall success rate was still disappointing. The problem here was not the mechanics of the operation or the initial performance of the new heart. It was the mismatch between the recipient’s immune system and the donor’s heart. Although the donor’s heart is matched as closely as possible to the patient’s major tissue types, the immune system must be suppressed to stop the heart from being rejected. Drugs to suppress the immune system were not very sophisticated in the early days, but the development of ciclosporin in the early 1980s revolutionized immunosuppression and greatly improved the success of heart transplants. Now, it is a victim of its own success, and far more people are needed for transplants than there are donors. Only around 200 transplants are carried out in the UK each year despite more than 750,000 having heart failure, and similar figures are seen around the world. To fill this gap, scientists are genetically modifying pigs to make their hearts compatible with the human immune system so they can be transplanted into patients without rejection. This was extremely complex and challenging, but the first clinical transplants began in 2022.
However, heart transplantation has succeeded in reviving the search for the total artificial heart, with the more feasible goal of keeping the patient alive until a donor is found, or a so-called “bridge to transplant”. Over the years, artificial heart technologies have improved through changes to more biocompatible materials, better valve design, and more efficient handling of blood flow. Success was achieved: one study saw that 80 percent of the patients on the artificial hearts lived for more than a year, and some for 6 years. The longest time a patient was supported for a transplant was 1,373 days. But serious infectious complications were still common, and the goal of a complete “destination” therapy for artificial hearts was a distant dream.
Meanwhile, the urgent need for transplantation took the technology in another direction. Rather than completely replacing the failing heart, the idea was to support it by aiding blood flow. The ventricular assist device, or VAD, took blood out of the ventricles of the heart in a completely different way and pushed it into the aorta at high pressure. This increased the ejection of blood from the heart and thus increased the effective cardiac output. It also solved another problem faced by engineers of complete artificial hearts – how to balance the flow of blood to the right and left sides of the heart. The amount of blood circulating in the left ventricle/body loop must be very close to that in the right ventricle/lung loop. With 100,000 beats a day, even a teaspoon of difference would put up to 500 liters of blood in the wrong place with each beat. The heart has developed complex biological mechanisms to ensure this doesn’t happen, but engineers have had huge battles trying to do the same with feedback systems. In the case of VADs, the left ventricle can be supported independently (or more commonly) with the left ventricle, obviating this problem.
Left ventricular assist devices, or LVADs, have revolutionized care for end-stage heart failure. More than 15,000 LVADs have now been implanted worldwide, and about a third of patients with end-stage heart failure are now supported on LVADs. The intention is usually to transfer the patients to a transplant, but in reality the lack of donor hearts means that patients can often wait on LVAD support for years. Survival rates of over 50 percent are seen at seven years, and there are reports of patients living up to 13 years on these devices. LVADs are therefore a therapy in themselves by default. Again, technology has progressed, with newer LVADs performing better. The idea was to stop imitating the heart, with its pulsating action, and move to a continuous flow of blood. Rotating paddles (impellers) push the blood forward in a continuous motion, creating a smooth, uninterrupted flow. This has the odd side effect of creating a patient without a pulse, which can undoubtedly be uncomfortable for the doctor as well as producing some unwanted side effects as the body adapts for the new flow. External battery packs are still an inconvenience and a source of infection, but systems are being developed that transfer energy transcutaneously (across the skin) based on induction (like home induction stoves). The LVAD units would still need a small implanted battery in case the temporary device failed – and handbag thieves have been known to steal external battery packs from patients!
The search for a fully implantable artificial heart continues. The biggest hurdle is trying to develop external transcranial units to fully power the demands of the heart. Specifications for a complete artificial heart require it to pump eight liters per minute of blood against a blood pressure of 110 mmHg. (The biological power storage molecule adenosine triphosphate (ATP) would be needed in quantities of more than half your body weight per day to power your own heart to do so, if ATP was not continuously renewed in cells.) Compressors are miniaturized to be larger. portable, but it was a struggle to make them fully implantable. Here it seems that the VAD technology could hold a solution, dispensing all compressors and using the impeller devices instead, with dual right and left VAD working together.
The solutions seem very close, but no one expects an easy ride. The many failures over the years have certainly left scientists in awe and in awe of the natural engineering of the heart.
Sian E. Harding is Emeritus Professor of Cardiac Pharmacology at the National Heart and Lung Institute at Imperial College London, where she headed the Division of Cardiovascular Sciences and the BHF Center for Cardiac Regeneration. She is the author of “The Exquisite Machine,” from which this article is excerpted.
