by This article is an excerpt from Sian E. Harding’s book “The Exquisite Machine: The New Science of the Heart.” It was originally featured in the MIT Press Reader.
Nothing demonstrates the heart’s perfect construction more clearly than our own failed attempts to imitate it. This history of the fully artificial heart is characterized by both brilliant innovation and continuous clinical failure. In 1962, John F. Kennedy challenged the scientific community to land a man on the moon and bring him safely back to Earth by the end of the decade. In 1964, cardiovascular surgeon Michael DeBakey persuaded President Lyndon B. Johnson to fund a program to develop the first workable, self-contained artificial heart and began a race to successfully manufacture one before the moon landing. In 1969 both goals were apparently achieved when the Texas Heart Institute implanted the first fully artificial heart just three months before the Apollo 11 launch. However, while the moon landings have led to the Space Shuttle, the Mars Rover and the International Space Station, and (despite a long hiatus) the latest goal of developing a lunar base to take us to Mars, a reliable, off-the-shelf artificial heart is still around just out of reach.
The artificial heart was originally intended to be a lifelong replacement for the failing organ. This was a high bar as the first design had an external compressor with an air line through the skin into the patient’s body. Compressed air inflated and deflated Dacron bags or sacs, which collapsed and expanded to displace blood from a surrounding sac. While having the compressor outside the body was useful as the mechanical parts (which were most susceptible to wear and tear) could be easily replaced, this would result in a bulky device that would have to be wheeled around with the patient. It was hard to imagine how this could be given to a patient and expected to lead a partially normal life for many years.
However, the history of the artificial heart is also intertwined with that of heart transplantation. This was again just a hopeful dream in the early 1960s, but in 1967 cardiac surgeon Christian Baarnard performed the first successful transplant in Cape Town. Now the purpose of those first artificial hearts has been changed. They didn’t have to be suitable for life; Their purpose was to keep the patient alive until a transplant donor could be found. As with many very experimental therapies, the first case was performed on a patient who had run out of options. A 47-year-old man underwent surgery to repair a giant left ventricle aneurysm that had thinned and swollen the heart wall. He was assisted by a heart-lung machine, which bypassed the heart and allowed blood to flow throughout the body. However, he could not be weaned off the machine at the end of the operation because his heart was too weak. He was in dire need of a transplant. Denton Cooley, DeBakey’s associate, offered him the new experimental artificial heart and he accepted. The patient was kept stable with the new device for 64 hours until a matching donor heart was found and then transplanted.
Only about 200 transplants are performed in the UK each year, despite more than 750,000 people living with heart failure, and similar numbers are seen worldwide.
This initially appeared to be a triumph for the total artificial heart, but tragically the patient died of sepsis 32 hours later. Not only that, the device had damaged both the blood and kidneys, and the walls of the expandable sacs were covered with blood clots. This heralded a series of problems that would continue to thwart the scientists and engineers wrestling with the process. Infection and sepsis are a constant challenge for any device that requires a wire to be constantly passed through the skin. Devices that move the blood change its composition, and the foreign surfaces cause the blood to clot, leading to strokes and blood failure. The first Jarvik heart, one of the next iterations, was implanted in five patients and one lived 620 days. But two of the patients suffered severe strokes, and eventually all died from either sepsis or blood problems.
The heart transplant also got off to a shaky start, with Baarnard’s first patient dying after just 18 days. The first patient in the UK to have a transplant performed by cardiothoracic surgeon Donald Ross at London’s National Heart Hospital survived just 45 days and the overall success rate has remained disappointing. The problem here was not the mechanics of the surgery or the initial performance of the new heart. It was the mismatch of the recipient’s immune system to that of the donor heart. Even if the donor heart is as closely matched to the patient as possible with the most important tissue types, the immune system must be suppressed to prevent rejection of the heart. Immune suppression drugs were not very sophisticated in the early days, but the development of ciclosporin in the early 1980s led to a revolution in immunosuppression that dramatically improved the success of heart transplants. Now it is a victim of its own success as there are many more people in need of a transplant than there are donors. Only about 200 transplants are performed in the UK each year, despite more than 750,000 people living with heart failure, and similar numbers are seen worldwide. To fill this gap, scientists have genetically modified pigs to make their hearts compatible with the human immune system so they can be transplanted into patients without rejection. This has proven very complex and challenging, but the first clinical transplants began in 2022.
However, the success of heart transplantation had reinvigorated the quest for the total artificial heart, with the more achievable goal of keeping the patient alive until a donor is found, or “bridge to transplantation,” as it is called. For decades, artificial heart technologies have improved with changes toward more biocompatible materials, better valve design, and more efficient blood flow management. Success has been achieved: In a study, 80 percent of patients with artificial hearts survived for more than a year, some even for 6 years. The longest time a patient was assisted with transplantation was 1,373 days. But severe infectious complications were still common, and the goal of full “target” therapy for artificial hearts was still a distant dream.
Meanwhile, the urgent need to create a bridge to transplantation had taken technology in a different direction. Instead of completely replacing the failing heart, it should be supported by blood flow support. The Ventricular Assist Device (VAD) took blood from the ventricle of the heart in a completely different way and pushed it into the aorta at high pressure. This increased the blood output from the heart and thereby increased the heart’s effective output. It also solved another problem artificial heart engineers encountered – how to balance right and left heart blood flow. The amount of blood circulating in the left ventricle/body loop must be very similar to that in the right ventricle/lung loop. At 100,000 beats per day, even a teaspoon difference would result in 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 great struggles trying to achieve the same with feedback systems. With VADs, either the right (or more commonly) the left ventricle can be independently assisted, eliminating this problem.
Left ventricular assist devices, or LVADs, have revolutionized the treatment of end-stage heart failure. More than 15,000 LVADs have now been implanted worldwide, and approximately one-third of end-stage heart failure patients are now treated with LVADs. The intent is usually to bridge patients through to transplantation, but the shortage of donor hearts actually means patients can often remain on LVAD support for years. Survival rates in excess of 50 percent are observed after seven years, and there have been reports of patients living up to 13 years with these devices. LVADs have therefore become a standard therapy in their own right. Again, technology has advanced, with newer LVADs performing better. A groundbreaking idea was to stop imitating the pulsating movement of the heart and to switch to a constant flow of blood. Rotating paddles (impellers) propel the blood in a continuous motion, creating a steady, uninterrupted flow. This has the odd side effect of creating a patient without a pulse, which can be disconcerting to the unsuspecting doctor and creates some unwanted side effects as the body adjusts to the new flow. External battery packs are still an inconvenience and a source of infection, but systems are being developed that transmit energy transcutaneously (through the skin) based on induction (like household induction cookers). The LVAD units would still require a small, implanted battery in the event of a transient device failure – and external battery packs have been known to be snatched from patients by handbag thieves!
The search for a fully implantable artificial heart continues. Trying to develop external transcutaneous devices to fully meet the heart’s needs is the biggest hurdle. The specifications for a total artificial heart call for it to pump eight liters of blood per minute against a blood pressure of 110 mmHg. (The biological energy storage molecule adenosine triphosphate [ATP] would be needed in amounts greater than half your body weight per day to fuel your own heart if ATP were not continually renewed in cells.) Compressors have been miniaturized to be more portable, but it has been a struggle to find them to produce fully implantable. Here VAD technology seems to offer a solution that completely dispenses with compressors and instead uses impeller devices where two right and left VADs work together.
Solutions seem tantalizingly close, but no one expects an easy ride. Surely the many failures over the years have inspired scientists with humility and reverence for the heart’s natural engineering.
Sian E Harding is Professor Emeritus of Cardiac Pharmacology at the National Heart and Lung Institute, Imperial College London, where she led 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 extracted.
