The need to mend broken hearts has never been greater. But what if we could simply manufacture a new one?
Haskell Karp was 37 when he suffered his first heart attack, and over the next ten years he suffered a variety of related problems. By 1969 even the slightest effort, like combing his hair or brushing his teeth, would bring on chest pain or extreme shortness of breath. There are four grades of heart failure under the classification determined in 1928 by the New York Heart Association; Karp’s was classified as grade IV, the most severe.
The surgeon who treated him at St Luke’s Hospital, Texas, in 1969 was an energetic man called Denton Cooley. “The man had a big dilated heart and I hoped we could reduce the size of that heart, so it could regain some of its own function,” says Cooley. But Karp did not respond well to the treatment; half of his heart was beyond repair. Cooley had expected this. He’d discussed it with Karp before the surgery: “I don’t think your heart’s going to be strong enough to tolerate this operation,” he’d told him. But Cooley had made a suggestion: if Karp’s heart were to be too weak at the end of the operation, how about taking a replacement – an experimental artificial heart they’d been developing in the lab.
The mechanical heart was a temporary ‘bridge’, intended to provide additional time for patients waiting for a donor heart to become available. It had an implantable part, larger than a human heart, connected to an exterior console the size of an upright piano powering it. The contraption drove compressed air through two hoses made of silicone and fabric (which entered the patient’s body below the ribcage) and into the chambers of the artificial heart: one side a left pump, the other a right, each with a balloon inside. When the chamber filled with blood, the balloon filled with air and pushed the blood out, keeping Karp alive.
The need to mend broken hearts has never been greater. In the USA alone, around 610,000 people die of heart disease each year. A significant number of those deaths could potentially have been prevented with a heart transplant but, unfortunately, there are simply too few hearts available.
Until fairly recently, doctors were limited in how much they could do when a heart breaks. The first notable milestone took place in 1912, when the French surgeon Théodore Tuffier used his fingers to dilate a patient’s aortic valve (which helps control the flow of blood out of one side of the heart). But it was the first ‘blue baby’ operation at Johns Hopkins Hospital in Baltimore, Maryland, in November 1944 that symbolised to some the real dawn of heart surgery. Following a diagnosis by his colleague Helen Taussig, Alfred Blalock joined a baby girl’s aorta (the main artery leaving the heart) to her pulmonary artery (leading to the lungs), giving the blood a second chance at oxygenation and relieving the lack of oxygenated blood that gave the infant her distinct blue cast.
Yet the possibility of doing more to fix the inside of the heart remained impossible for years; opening it meant the death of the patient within minutes. What was needed was something that would stop the blood flow into the heart’s chambers, so it could be operated on, but that would keep the blood flowing around the body so the vital organs were not deprived of oxygen. That would take until 1953, when the first successful open heart surgery using a heart–lung machine took place at the Jefferson Medical College in Philadelphia.
Even so, the only solution for many people with heart problems was – and still is – a transplant with a healthy, natural heart. In 1967 the South African surgeon Christiaan Barnard performed the world’s first human heart transplant in Cape Town. It seemed like a starting gun had gone off; soon doctors all around the world were transplanting hearts.
The problem was that every single recipient died within a year of the operation. The patients’ immune systems were rejecting the foreign tissue. To overcome this, patients were given drugs to suppress their immune system. But, in a way, these early immunosuppressants were too effective: they weakened the immune system so much that the patients would eventually die of an infection. It seemed like medicine was back to square one.
The origins of the world’s first artificial heart lie with Michael E DeBakey, Denton Cooley’s former mentor. A titan of American heart surgery, DeBakey was known as ‘the Texas Tornado’. “He was mean as hell,” says Oscar Howard ‘Bud’ Frazier, one of the many surgeons trained under the Tornado. He ran his hospital like a marine training camp, with most residents working up to 72 hours on a regular basis. Once he fired seven chiefs of department at the same time because they failed to meet his standards. But DeBakey’s exacting standards helped establish Baylor Medical School, and his funding campaigns helped kick-start research into various devices – including the artificial heart. “We would never have these devices without him,” says Frazier.
Indeed, DeBakey is widely credited for starting the field of artificial heart surgery with a 1964 grant from the National Heart, Lung and Blood Institute (NHLBI). The 1969 device used on Karp was the product of this, but at the time it had only been tested on calves, and none of the animals had survived for more than a few hours. It had never been tested in human patients. Until Haskell Karp.
The thing is, Cooley didn’t actually tell DeBakey what he was going to do. When Karp went under the knife, DeBakey was at the NHLBI in Washington DC, appealing for additional funding. Unbeknownst to him, two of his protégés had been making tweaks to the artificial heart for months. In his book 100,000 Hearts: A surgeon’s memoir, Cooley tells how he was brought the device in December 1968 by Dr Domingo Liotta, a research fellow in DeBakey’s lab. Frustrated under DeBakey’s leadership, Liotta (according to Cooley) thought his life’s work was being cast aside as DeBakey began to have doubts about the feasibility of a totally artificial heart and became more interested in developing pumps for a ‘partial’ device that would bolster the patient’s own organ.
And so the story, according to DeBakey, goes that in 1969 Denton Cooley took the device and implanted it without permission so that he could be the first to implant an artificial heart. Cooley and Liotta had altered the design of the valves and renamed the device ‘the Cooley-Liotta heart’, intending it as an emergency bridge while patients were waiting for a heart transplant.
The professional fallout was bad. DeBakey first heard about the operation from the press, who – knowing he was in Washington – had gone knocking on the door of his hotel room for comment. DeBakey called Cooley a thief. He considered it a betrayal, a childish act to claim a medical first. The feud lasted for 40 years and made the cover of Time magazine in 1970.
Time and again, Cooley has defended his behaviour. He says he was only ever driven to try the desperate move to save a life. Which he did, for a time. Haskell Karp lived longer than any of the cows DeBakey had operated on – long enough to find a donor heart. After 64 hours with the artificial heart, Cooley transplanted in a natural donor heart. But Karp died 36 hours later of pneumonia and kidney failure. Karp’s wife later sued Cooley, claiming he’d never told them that the artificial heart was experimental. Cooley successfully defended his action in court.
Seventy-four years old with a full head of white, floppy hair, Bud Frazier is still visibly affected by the moment he literally held the life of a young man in his hands.
It was 1965, and Frazier was in medical school. The patient was about 18 years old and had a problem with one of his heart valves. He was sent over from Italy, where no heart surgery was performed at the time. Italian patients were mainly sent to the USA, most of them treated by either DeBakey or Cooley.
During the surgery, led by DeBakey, the young man’s heart stopped and Frazier was asked to take it in his hand and massage it to keep the blood circulating. At one point the young man even regained consciousness and looked Frazier right in the eye. The problem was that the man’s heart did not start beating by itself. After a while, DeBakey told Frazier to stop: “We can’t save him,” he said. The chief resident agreed. They both told Frazier to stop. He didn’t want to. Stopping would kill the man. But it was no use; the heart wasn’t responding. Eventually, Frazier had to stop.
That was almost 60 years ago, but he can still hear the cry of the mother whose son he could not save. The death inspired an all-consuming thought in Frazier: “My god, if I can do that with my hand, we must be able to develop something we can pull off a shelf that does the same thing.”
After medical school Frazier served in the Vietnam War. He returned to Texas and Baylor Medical School in 1971, keen to work on heart pumps. But after the artificial heart incident, DeBakey had fired Liotta and got rid of everyone else in the lab. The whole pump programme was dead, but it restarted at the nearby Texas Heart Institute with one Denton Cooley at the head.
By then Cooley was doing more heart surgery than anyone else in the world. Frazier made the difficult decision to leave DeBakey’s lab and finish his residency across the road. DeBakey didn’t talk to him for ten years.
By the mid-1960s, as open-heart surgery began to take place around the world, Texas Heart Institute doctors were doing more than at all of the other hospitals in the USA combined. Houston had wealthy oilmen who wanted to do something meaningful with their money, and the hospitals were more than willing to receive their philanthropy.
Today, Houston is home to the Texas Medical Center, one of the world’s largest medical complexes. It’s located three miles south of Houston’s Midtown and resembles a financial district, with its many skyscrapers stretching into the clear blue sky and glistening in the Houston sun. It is home to 21 hospitals, 13 support organisations, eight academic and research institutions, three medical schools, two universities, a dental school and over 100,000 workers – more than at Apple or Google – in an area nearly the size of Gibraltar. And in 2014, more heart surgeries were performed here than anywhere else on the globe, many of them by Bud Frazier.
“It’s a tough business, the heart transplant business,” says Frazier. As he puts it, “you just guarantee them a premature death”, though less premature than would otherwise be the case. Half of transplant patients die within ten years, and only about 10 per cent live 20 years. Outside his office hangs the picture of a man who lived for 33 years. He was an exception.
The heart is basically a bag of muscle divided into four interior chambers. The two upper chambers are called atria, and the two lower ones are the ventricles. On the right side, deoxygenated (oxygen-poor) blood from the body and head flows into the right atrium, which pumps it down to the right ventricle. This chamber then pumps the blood out to the lungs. Meanwhile, on the left-hand side, oxygenated (oxygen-rich) blood from the lungs enters the left atrium, which pumps down into the left ventricle, and from there it passes to the body and head. Central to this system are four valves between each chamber, maintaining a one-way flow of blood by closing and preventing backflow when the heart’s chambers contract, pumping blood.
There are plenty of causes for heart failure. That’s why, like ‘cancer’, it is used as an umbrella term that is the outcome of a whole host of conditions: high blood pressure, coronary heart disease, valve damage and heart muscle weakness (cardiomyopathy), which itself may have various underlying causes. When the heart gets sick, the cells within it gradually weaken and tire, resulting in the heart getting stretched out like lace in bad underwear. It gets bigger and bigger. With the increase in size, its ability to pump decreases. Heart failure occurs when the heart is no longer able to pump blood at all because, in essence, that’s all it is: a pump, albeit a pretty important one.
After the Cooley-Liotta heart made headlines, a host of scientists started work on their own artificial hearts. Perhaps the most influential device was kick-started by Willem Kolff, the physician-inventor who produced the first kidney dialysis machine. Kolff invited a fellow medical engineer, one Robert Jarvik, to work with him at the University of Utah, and the result was the Jarvik-7. Made up of two pumps, two air hoses and four valves, the Jarvik-7 was more than twice as big as a normal human heart and could only be implanted in the biggest patients – mainly adult men. The external console for the Jarvik-7 was a little smaller than the piano-sized console for the Liotta-Cooley heart. It had wheels, was as big and heavy (although not as tall) as a standard household refrigerator, and was normally connected to sources of compressed air, vacuum and electricity.
In 1982, Jarvik and Kolff won approval from the US Food and Drug Administration to use it in human patients and implanted it that same year. Their first patient was a 61-year-old dentist called Barney Clark, who lived on the Jarvik-7 for 112 days. A second patient was implanted in 1984 and died after 620 days. History records a total of five patients implanted with the Jarvik-7 for permanent use, all of whom died within 18 months of the surgery from infections or strokes.
In the years following its creation, the Jarvik artificial heart went through trials more financial than medical. In 1990 its manufacturer Symbion, Inc. (initially owned by Kolff and Jarvik) was closed and use of the Jarvik stopped after it could no longer keep up with FDA reporting requirements. Academia and business – in the form of the University Medical Center in Tucson, Arizona, and MedForte Research Foundation, a noncommercial research organisation in Salt Lake City, Utah – combined to save the Jarvik technology by purchasing the patent. The device has been tweaked and renamed many times; at the time of writing, it was the world’s only FDA-approved total-replacement artificial heart device used as a bridge-to-transplant for patients.
The surgeon who holds the record for the most artificial heart surgeries, as well as the record for the most heart transplants (more than 1,100 at last count), is Bud Frazier. And the device he has implanted the most is a direct descendent of the Jarvik-7, the SynCardia. It replaces both of the patient’s own ventricles. The SynCardia is sewn to the patient’s remaining atria (the top half of the heart) and has two hoses that pierce the skin, connecting to all of the sensors, motors and electronics that power it. They are housed in a driver the size of a lunchbox, carried as a backpack outside the body – although at 13 pounds, it’s not lunchbox-light. And actually, it’s not a whole lot different from the Cooley-Liotta device from the 1960s or the Jarvik from 1982. “Yeah, it’s got some cool alarms and the mechanism, but it’s still pistons going up and down with motors driving air in and out,” says Frazier’s colleague Dr William (Billy) Cohn.
The current version of the SynCardia is heavy and cumbersome, and the hoses piercing the skin mean the risk for infection remains high. “It’s primitive,” says Cohn. “It’s a bath toy…it really looks like a bath toy.” But, he adds, “it’s brilliantly designed, because it’s so simple”, which perhaps explains why the design has remained relatively unchanged for more than 25 years. And it’s efficient enough to enable patients to return to active lifestyles – because the device can be carried in a backpack, some patients can even play tennis or ride bikes.
The main issue for Frazier and Cohn is that it has a limited lifespan. The current SynCardia model costs around US$100,000 and has to be replaced every three months because the internal components, which according to Cohn beat around 120,000 times a day, simply wear out. And so, like its Jarvik and Cooley-Liotta predecessors, it’s only really useful as a ‘bridge’ to keep patients alive until they can get a heart transplant.
Moreover – as Frazier tells me, Cohn nodding in the background – patients who have already had one transplant don’t do well on devices, because their whole heart fails. The only thing that will help is another totally new heart. “We have a patient now who has a pneumatic heart,” says Frazier. “He’s a young man. I did him when he was in his 20s and he rejected the heart when he was 30. We put [the SynCardia] in, and he’s had it in about three years. But it’s going to fail. We can already tell it’s failing, but we can’t transplant him either, because he’s got too many antibodies [which would reject a new heart] and we can’t get a donor [anyway].”
“It’s not working right,” he sighs. “It’s better than dying,” says Cohn.
The SynCardia is not a long-term solution to heart failure. Neither are many of the alternatives. In the early 2000s, the Massachusetts-based company Abiomed unveiled a new heart that (unlike the SynCardia) was designed to be permanent – a total replacement heart for end-stage heart failure patients who were not candidates for transplant and couldn’t be helped by any other available treatment.
The Abiomed AbioCor had an internally implanted battery, continually recharged from an external console or from a basic patient-carried external battery pack. As a result, there were no tubes or wires piercing the skin, so the chances of developing an infection were lower.
AbioCor was implanted in 15 human patients – five of those done by Frazier at the Texas Heart Institute. But still, the longest living patient went less than a year and a half before the device broke. Most patients went five to nine months. The device – which was the size of a honeydew melon – was, like its predecessors, still too big and too difficult to implant. The last AbioCor implant was in 2009. Again, it seemed like medicine was back to square one.
Yet maybe that’s no bad thing. All these versions of artificial heart devices, whether they are meant to support the heart or replace it completely, are trying to copy the functions of the heart, mimicking the natural blood flow. The SynCardia, the AbioCor, the Jarvik, even the early Cooley-Liotta heart, would fill with blood and then forcefully eject it into the body. The result is what’s called a pulsatile pump, the flow of blood going into the body like a native heart, at the average of 80 spurts a minute needed to sustain life. That’s the cause of the gentle movement you feel when you put your fingers to your wrist or your chest – your pulse, which corresponds with the beating of your heart.
Today, Frazier, Cohn and the Texas Heart Institute are working on a new wave of artificial hearts with one crucial difference: they don’t beat.
The Archimedes’ screw was an ancient apparatus used to raise water against gravity. As its name suggests, this third-century device is widely considered to have been invented by the Ancient Greek polymath Archimedes. Essentially, it is a screw in a hollow pipe; by placing the lower end in water and turning it, water is raised to the top. The device was used mostly for draining water out of mines or other areas of low-lying water. In 1976, during voluntary medical mission work in Egypt, cardiologist Dr Richard K Wampler saw two men using one such device to pump water up a river bank. He was inspired. Perhaps, he thought, this principle could be applied to pumping blood.
The result was the Hemopump, a device as big as a pencil eraser. When the screw inside the pump spun, blood was pumped from the heart to the rest of the body. At the time there were no motors small enough to fit inside an implantable device, so Wampler had the motor outside sit on the patient’s leg and had a spinning cable threaded up the patient’s leg artery to the pump. Naturally, the first doctor to implant this device – initially in a cow and then in a patient – was one Bud Frazier, in April 1988.
The Hemopump was the world’s first ‘continuous flow’ pump. Rapidly spinning turbines create a flow like water running through a garden hose, meaning the blood flow is continuous from moment to moment. Because of this, there is no ejection of the blood in spurts. There is no ‘heartbeat’. The patient’s own heart is still beating but the continuous flow from the device masks their pulse, meaning it is often undetectable at the wrist or neck.
It was a temporary device and could only be used while the patient was lying flat in bed. The Hemopump was not meant as a replacement for the heart; its primary function is actually to ease the heart’s burden and give it a rest. Like a wheelchair for the heart, it was intended for recuperation. Yet the Hemopump still had its problems. Because a tube had to be inserted through the femoral artery, and then moved up until the tip of the tube had passed over the aortic valve, it couldn’t be used in 20 per cent of patients because the tube was too large. In addition, at the time there were no motors powerful enough to turn the turbines as fast as they needed to go, and in early studies the cable would break too. Eventually, financial backing dried up, and by the early 1990s the Hemopump had fallen out of use.
It lives on in spirit, however. Abiomed’s newest heart prototype, Impella, uses similar technology boosted by leaps in modern engineering. It has a motor so small it sits inside the device at the end of the catheter, rather than outside of the body. The Impella is the smallest heart pump in use today – it’s not much bigger than a pencil – and as of March 2015 has been approved by the FDA for clinical use, supporting the heart for up to six hours in cardiac surgeries. Meanwhile, at the Texas Heart Institute, Frazier and Cohn – inspired by Wampler – have been working on their own Archimedes’ screw. The HeartMate II, like the Hemopump, doesn’t replace the heart but rather works like a pair of crutches for it. About the size and weight of a small avocado, the HeartMate II is suitable for a wider range of patients than the SynCardia and has, on paper, a significantly longer lifespan – up to ten years. The key is the screw technology: the spinning propeller creates less friction than pulsatile artificial heart devices, reducing wear and tear. Since its FDA approval in January 2010, close to 20,000 people – including former US Vice President Dick Cheney – have received a HeartMate II, 20 of whom have been living with the device for more than eight years. All with an almost undetectable pulse.
Animal trials for the next iteration are already underway. The HeartMate III is down to the size of a yo-yo, and the spinning part uses magnetic levitation technology – similar to the kind used in some super-fast Maglev trains in China, Germany and Japan. “Without any flexible membranes or valves, or mechanical bearings, there wouldn’t be problems with mechanical wear,” says Cohn.
On 20 January 2015, in an operation that took more than eight hours, I watched a small calf named Chicle (meaning ‘gum’ in Spanish, because she kept chewing all night) have her heart replaced by two HeartMate III devices. Chicle, along with the 75 or so calves before her, is a subject of the experiments Frazier and Cohn are performing at the Texas Heart Institute. The purpose is to see whether the body tolerates completely pulseless circulation; “to try to understand what Mother Nature will tolerate, and what she won’t,” says Cohn.
The next day I accompanied Chicle’s operating surgeon, Cohn, to see how she was doing. She was calm and still chewing, seemingly happy, and alive with no pulse.
Before the Heartmate III has even been tested on humans, the next generation of pulseless artificial hearts is already on its way. Called BiVACOR (a rotary ‘Biventricular Assist Device’), it also uses magnetic levitation technology. The key difference, says Cohn, is that unlike previous devices, this one is meant as a total replacement heart – one that could, at least on paper, last forever.
In early tests the BiVACOR proved extremely power efficient compared to previous artificial heart devices. Because it requires less power to run, it has the potential to run for longer periods on internal batteries, says Cohn. The current version will run on around 10 watts and have internal batteries that can power it for 2–3 hours in the event of a disconnect from the battery pack worn in a vest outside the body. The ultimate goal is to have a wireless system and to power the device through the skin using inductive coupling, the magnetic field principle used to charge electric toothbrushes. Cohn imagines a coil under the skin and one outside of the skin: no wires required, just an oscillating magnetic field doing the charging. This would also mean there wouldn’t be any breaks in the skin, thus – like the pioneering AbioCor before – reducing the risk of infection.
BiVACOR was the brainchild of Daniel Timms, an Australian engineer who first sketched out his idea some 15 years ago. A chance meeting at a Singapore conference brought him to the attention of the Texas Heart Institute researchers. When Frazier and Cohn saw his idea in September 2011, they called it the most highly evolved and brilliant plan for a total artificial heart they’d heard to date. They helped raise around US$2.5 million of private funding in just one week for Timms, who formed a for-profit company (also called BiVACOR) and moved his entire team to the Texas Heart Institute labs for development and testing.
Cohn says he is often chastised for his unbridled confidence in BiVACOR and his claims that it could “last forever”. He shows me a box filled with nearly a hundred 3D-printed prototypes for the BiVACOR rotor, each with a subtle difference in shape. The team is running constant experiments, he says, using 40 per cent glycerin solution to imitate blood. They have already developed rotors that work extremely well but believe they can improve the design further. Thus far, they are on course to start animal studies in late 2016 and, if successful, could start human studies as early as 2019.
I try to imagine a world full of people with no pulse. How, in such a future, would we determine if a person were alive or dead? “That is very easy,” says Cohn, bringing my existential philosophising to a halt. “When we pinch our thumb and it goes from pink to white and immediately back to pink, this means blood is flowing through the body. You can also tell if someone is still alive if they are still breathing.”
He admits that once more of these devices are implanted into patients we will need a standard method of determining such a person’s vitals. Cohn imagines them wearing bracelets or even having tattoos to alert people to their pulseless state.
I wonder how people will take to hearts that literally don’t beat. Perhaps it will be the same as when patients were offered the first heart transplants: resistance, followed by acceptance due to overwhelming need.
“Any new procedure is going to have critics,” says Frazier’s mentor, the indefatigable Denton Cooley. “On the day that Christiaan Barnard did the first heart transplant, the critics were almost as strong, or stronger, than the proponents of [artificial] heart transplantation,” he says. “A lot of mystery goes with the heart, and its function. But most of the critics, I thought, were ignorant, uninformed or just superstitious.”
Cooley performed the first US heart transplant in May 1968. And at 94 years old he still treasures the memory of the day he implanted the first artificial heart into Haskell Karp and the “satisfaction that came from seeing that heart supporting that man’s life”.
“I had always thought that the heart has only one function, and that is to pump blood,” he says. “It’s a very simple organ in that regard.”