Lausanne, 12 June 1986
In the 1966 thriller Fantastic Voyage a submarine full of scientists is shrunk to microscopic size and injected into the body of a comatose man who has suffered an inoperable brain injury. Over the course of the next hour they navigate his veins and arteries, passing through his heart and locating a blood clot before vaporising it with a laser. It’s a fairly silly plot, but the interior of the human body is imaginatively portrayed as a hostile alien landscape, with anatomical details so accurate that the film was once routinely shown to medical students. Though it ends with a tribute to the ‘many doctors, technicians and research scientists’ who advised the producers, few cinema-goers can have believed that they had just watched a bold vision of the future. Miniaturising a submarine remains beyond our capabilities, but the central premise of Fantastic Voyage – that it would one day be possible to operate on the body from inside – has since come to pass.
Indeed, another film made the previous year showed that this improbable science-fiction dream was already well on the way to being scientific fact. It was intended only for a small audience of specialists, so the fifteen-minute Transluminal Angioplasty can be forgiven its mouthful of a title. It was written, directed and narrated by its star, the Oregon radiologist Charles Dotter, to demonstrate a technique he had invented for removing blockages inside blood vessels. Rather than attack the problem from outside the body, he had hit upon the idea of treating it from within. A flexible catheter was inserted through a small nick in an artery near the skin and gently pushed through the obstruction to create a new channel for the blood. The patient remained awake, and the entire procedure took less than an hour. This was a radical departure from the conventional method of making a large incision under general anaesthetic and opening the artery to clean it. The point is driven home in the film by a montage of gory surgical images – scalpels carving through flesh, needles submerged in bubbling pools of blood – which are then contrasted with the serene and bloodless scene as Dotter gently navigates his catheter towards its unseen destination, exchanging pleasantries with his patient as he does so. In this brief demonstration it is an artery in the leg which is being treated, but Dotter also suggests that the technique might one day be used in the vessels of the heart.1 Little more than a decade later his prediction would come true, opening a new era in the treatment of cardiac disease.
For decades, doctors concerned with the workings of the heart had been divided into two camps: cardiologists and surgeons. The role of cardiologists was diagnosing cardiac conditions and treating them with drugs; if nothing else was suitable, patients would then be referred for surgical treatment. But in the 1970s something interesting happened: cardiologists began to ‘operate’ on the heart. This was nothing short of a revolution. Within a few years it became possible to treat coronary artery disease, and to repair congenital defects and even faulty valves, using nothing more than a flexible tube introduced through a tiny needle puncture. This new discipline, interventional cardiology, changed when and how surgery was undertaken, and made some complicated and dangerous operations entirely unnecessary.
The idea of introducing probes into the living heart was not a new one even then. In the nineteenth century several French physiologists did so in order to measure the temperature or pressure of blood within the cardiac chambers, making an incision in the neck of a dog or horse and pushing a tube through the blood vessels until it lay inside the organ. One of them, Claude Bernard, coined the term by which the technique is still known: cathétérisme (catheterisation).2 In choosing this word Bernard was acknowledging the similarity between the method and the ancient practice of inserting a draining tube (catheter) into the bladder to relieve urinary retention. His contemporaries Auguste Chauveau and Étienne-Jules Marey used a catheter to investigate the sounds of the heartbeat, proving that the apex beat, the vibration palpable on the outside of the chest, is simultaneous with the contraction of the ventricles.3
Catheterisation provided many important insights to later physiologists, but none was yet brave enough to use it on a human subject. That important step had to wait until the late 1920s, and the work of a young German who was obsessed with the work of Chauveau and Marey. As a student at the University of Berlin, Werner Forssmann came across a picture of Marey holding a catheter which he had just inserted through a horse’s jugular vein and into its heart; as he recorded in his autobiography, ‘I was so excited by this image that it haunted me day and night.’4 Forssmann was frustrated by the shortcomings of contemporary methods of cardiac diagnosis, which still relied heavily on the stethoscope; X-rays and the ECG were also in use in larger hospitals, but gave only limited data. He believed that the methods of the French physiologists could be safely adapted for human use, and might provide a wealth of new diagnostic information.
Forssmann was twenty-four, newly qualified and working in a small hospital in the town of Eberswalde when he put his idea into practice. In the summer of 1929 he began by testing the idea on cadavers, and found that a catheter inserted into a vein in the elbow and gently pushed would find its way naturally to the right side of the heart. He then approached his boss, the surgeon Richard Schneider, to explain his plan of doing the same in a living subject. Schneider was sympathetic to his aims, but prohibited him from experimenting on patients. Forssmann offered instead to try the procedure on himself, but this too was forbidden. Schneider, who was friendly with the young man’s mother, pointed out that she had lost her husband in the recent war, and he had no desire to tell her that her son had killed himself performing some rash experiment.5 Forssmann had been expecting this response, and so used all his charm to persuade a theatre nurse, Gerda Ditzen, to help him. When she heard about his idea and was assured that it was entirely safe, she gamely volunteered to be his guinea pig.
One afternoon when most of the staff were taking their siesta, Forssmann and Nurse Ditzen made their way to an empty operating theatre. Forssmann explained that the local anaesthetic he intended to use might make her drowsy, so suggested that she lie on the operating table. This was a ruse; not content with disobeying his boss, Forssmann was also going to trick his accomplice. With ostentatious care he sterilised a patch of her skin with iodine, but out of her sight he had already anaesthetised his own arm. As soon as the skin was numb he made an incision in the crook of his elbow, punctured the vein with a needle and inserted an oiled urinary catheter a short distance. It was then that he admitted his deception: the nurse was furious with him, but agreed to help him complete the procedure. With the catheter tip embedded somewhere near his armpit he walked down several flights of stairs to the basement room where the X-ray equipment was housed. A colleague tried to talk him out of continuing with the experiment, but Forssmann was not to be denied. A strategically placed mirror allowed him to see an X-ray image of his own chest on the fluoroscopy screen, as he carefully fed almost two feet of rubber tubing into his own arm. There was no way of knowing in advance whether this would be painful, but the only sensation Forssmann felt was a slight warmth as the catheter slid along the wall of the vein. Finally the picture showed the catheter tip lodged in the right atrium of his heart, and a photograph was taken as proof of what he had done.6
When his superior Dr Schneider heard that his strict instructions had been disobeyed he was incensed, and reprimanded Forssmann for his dishonesty. But his ire was soon spent, and when the young man apologised he was congratulated on his ‘great discovery’ and invited for a celebratory dinner. Forssmann felt that the cardiac catheter might be a convenient way of introducing drugs directly to the heart, and shortly afterwards used the technique on a desperately ill patient who was suffering from peritonitis, the result of a burst appendix. A cardiac stimulant was injected through the catheter; although the patient appeared to rally briefly, she died shortly afterwards.7 Encouraged by Schneider, Forssmann wrote an academic paper about his experiences, which was published later that year by one of Germany’s most prestigious journals. Forssmann was not prepared for the uproar his work caused: he was accosted by journalists on the street, and his achievement was reported all over the world. One American newspaper remarked that ‘other men have performed feats quite as risky, but rarely does anyone try a thing that makes us fidget so much to think about it.’8
In the meantime Forssmann had moved to Berlin to continue his training with Ferdinand Sauerbruch, the pre-eminent surgeon of the day. An old-fashioned autocrat, Sauerbruch strongly disapproved of his junior’s experiment, and when he learned of it summarily dismissed him.9 Having endured a torrid couple of months in the Berlin hospital, Forssmann was far from unhappy with this outcome, and returned to Eberswalde to continue his research. He now saw that catheterisation might be a good way to obtain clear images of the heart and major vessels, which give only a faint outline in conventional X-rays. His idea was to inject contrast medium, a liquid opaque to X-rays, directly into the organ so that its structures would be clearly delineated in the resulting photograph. The theory was sound, but the equipment available to him was not terribly sophisticated and the images he obtained were disappointing.10 Despite the international acclaim that had followed his initial publication, Forssmann struggled to find any in the profession who would support his work, and he eventually gave up his research. Reflecting on the episode almost half a century later, he suggested that the medical establishment of the 1930s still regarded the heart as somehow sacrosanct: ‘I had committed the cardinal sin; I had broken into the sanctuary and wantonly destroyed a taboo.’11
There was little interest in catheterisation of the heart for the next decade, although a few researchers did try to continue investigations along similar lines. In 1936 a doctor from Paris, Pierre Ameuille, succeeded where Forssmann had failed, producing the first clear X-ray images of the structure of the heart.12 He faced hostility from his cardiologist colleagues, who denounced as ‘monstrous’ the idea of introducing a tube into the beating organ.13 But he found a more receptive audience in a former student, André Cournand, who was visiting Paris on a break from his job at a hospital in New York. Cournand was impressed by the images his old teacher showed him, and by his assurances that the procedure was perfectly safe. He also understood that the technique would be an ideal way of continuing his own research into the circulation, and when he returned to the United States shortly afterwards he took a stock of flexible catheters, which at that time were only manufactured in France.14
Cournand’s project was a thorough investigation of the cardiopulmonary system, the circulation of blood through the heart and lungs. He and his colleague Dickinson Richards were particularly interested in how lung disease affected the flow of blood, and thought that catheterisation would offer a precise method of measuring cardiopulmonary function. They refined their methods through experiments on dogs and a chimpanzee, and in 1940 they moved to working with humans.15 By using the catheter to measure the pressure in the right atrium, and the oxygen content of the blood before and after it passed through the lungs, they could calculate cardiac output, the volume of blood pumped by the heart each minute – a valuable way of assessing its health. Cournand was able to compare the cardiac outputs of four patients, one of whom had high blood pressure and heart failure; as expected, the damaged organ was pumping worryingly small amounts with each stroke.16
The technique was taken up more widely as those who had been trained by Cournand went to work at other institutions, and many of them had ideas about new ways in which the procedure could be used. In 1945 two groups discovered a way of using the catheter to diagnose congenital heart conditions. Eleanor Baldwin, a physician from New York, realised that the ability to take samples of blood direct from the cardiac chambers made it possible to detect cases of ventricular septal defect – until then difficult to diagnose with certainty. If a defect was present, oxygenated blood would be shunted from the left ventricle into the right and mingle with venous blood. Samples taken from the right ventricle via the catheter would therefore show unnaturally high oxygen concentrations when compared with those taken from the right atrium.17 Similarly, James Warren in Atlanta discovered that the presence of highly oxygenated blood in the right atrium was strong evidence of a hole in the septum between the upper chambers of the heart.18
Those outside the US trying to use cardiac catheterisation, however, often faced stubborn opposition. John McMichael, the first to adopt the technique in Britain, began work at a time when Nazi flying bombs were still making daily life in London extremely hazardous. When told that the catheter would cause blood clots and probably kill the patient, he responded by citing the remarkable statistic that in thousands of procedures since Forssmann’s first experiment in 1929, not a single death had occurred. He was also able to show that other congenital conditions could be diagnosed by catheterisation, including tetralogy of Fallot and pulmonary stenosis.19
McMichael was acutely aware of the debt he owed to the inventor of the method, who had seemingly disappeared from medical life: an article in The Lancet published in 1949 noted that ‘little is known about the fate of Forssmann’.20 After much effort McMichael finally tracked him down to a remote village in the Black Forest. The aftermath of the war had been difficult for him: after a spell in a prisoner-of-war camp he had returned home to discover that his house had been flattened in an air raid. He was soon reunited with his family, but his former membership of the Nazi party made it impossible for him to gain a position of any importance, so he settled down to life as a country doctor. He gratefully accepted McMichael’s invitation to visit London and talk about his work, finally gaining the recognition denied him almost twenty years earlier. His lasting reputation was assured in 1956, when he shared a Nobel Prize with Cournand and Dickinson Richards ‘for their discoveries concerning heart catheterization and pathological changes in the circulatory system’.21 Although urged to resume the research that had eventually made him famous, Forssmann refused: aware of how much the field had moved on in his absence, he resigned himself to the status of ‘living fossil’ – as he put it – and spent the rest of his career as a urologist.22
Until the late 1940s cardiac catheterisation was performed exclusively on the right side of the heart: this was easily done via a vein, since the catheter would be travelling in the same direction as the blood. Entering the left side meant passing it through an artery and against the flow of blood, which most clinicians thought too difficult and possibly dangerous. A few years earlier a doctor from Cuba, Pedro Fariñas, had shown that this was not the case, pushing a catheter to the base of the aorta in order to obtain beautiful X-ray images of the vessel and its major branches.23 Sliding it an inch or two further would have taken it through the aortic valve and into the left ventricle of the heart, but he felt that this was too risky to attempt. Henry Zimmerman, a cardiologist working in Cleveland, disagreed. He demonstrated that the procedure was perfectly safe, although it entailed a few difficulties not encountered when investigating the right side of the heart. He used an artery in the forearm to insert a catheter lubricated with olive oil, which then had to be pushed against the direction of the blood flow until it reached the aortic valve. Manipulating it beyond this obstacle was the trickiest step, since the valve is open for just a fifth of a second during each cardiac contraction.24 The first patient in whom he tried the technique had a leaking aortic valve, and Zimmerman was able to observe how this had affected the blood pressures in the aorta and left ventricle.25 A few years later a young cardiologist in Maryland, John Ross, devised an ingenious alternative to this technique. He designed a special catheter with a needle at its tip which was inserted through a vein and into the right side of the heart. A small puncture was then made in the septum and the catheter pushed through the hole so that it rested in the left atrium or ventricle.26 This avoided the difficulty of crossing the aortic valve, and the tiny wound in the cardiac septum was found to heal without complications.
The catheter was not just useful for measuring pressures and taking blood samples. In the early years of heart surgery, surgeons could never be entirely sure what they would find when they opened the patient’s chest: a child diagnosed with simple valve disease might turn out to have some exotic congenital problem. The 1950s saw rapid progress in visualising the vessels and interior of the heart, using the catheter to inject contrast medium direct into its chambers. An X-ray taken immediately afterwards would show their structure in far greater detail than had been achieved in earlier decades. The Stockholm-based researcher Gunnar Jönsson found that by precise manipulation of the catheter tip it was possible to choose the part of the circulation highlighted in the resulting X-ray, a technique known as selective angiography.27 That insight, and Mason Sones’s discovery that it was safe to inject the contrast liquid directly into the coronary arteries, were of crucial importance to the rapid evolution of open-heart surgery. An angiogram was a blueprint of the faulty cardiac plumbing which gave the surgeon a clear idea of what to expect and how to fix it.
In June 1963 Charles Dotter was invited to give a lecture to a gathering of radiologists in the spa town of Karlovy Vary in Czechoslovakia. He had been asked to talk about the future of angiography – a young discipline, but one whose role within medicine was well defined. As far as his audience were concerned, their job was to obtain X-ray images of the heart and major vessels in order to reach a diagnosis; surgeons or physicians would then decide on the most appropriate treatment. What they heard in the lecture theatre that day shocked them, for Dotter had far grander ambitions. He told his colleagues that they would soon be not just diagnosing patients, but treating them: ‘The angiographic catheter can be more than a tool for passive means for diagnostic observation; used with imagination it can become an important surgical instrument.’28 This was radical stuff: the idea that the catheter might be an alternative to the scalpel had not even occurred to most of those in the room. Dotter’s final words were greeted with a thunderous standing ovation; one of the attendees remembered later that ‘It was like a bomb had been dropped.’29
Dotter’s vision of the future was based on practical experience, not just wishful thinking. A few months earlier he had been performing an aortogram, a routine procedure to obtain X-ray images of a patient’s aorta. It entailed inserting a catheter via the femoral artery in the groin and into the abdominal aorta before injecting contrast medium. It was usually straightforward, but this time the femoral artery was obstructed by an atheroma – a fatty deposit caused by atherosclerosis. Dotter found that it took little effort to push the catheter through the obstruction, and without meaning to he provided a new channel for blood to flow through. This was such a simple procedure that he felt sure a catheter could be used routinely to clear a path through obstructed arteries.
Five years earlier a medical student in Cincinnati, Thomas Fogarty, had had a very similar idea. He was still in his early twenties when he invented a new instrument for removing blood clots from inside arteries. He had watched surgeons attempt to do so by making a wide incision through skin and blood vessel before using forceps to scoop up the clot – but this procedure had a disappointingly low success rate, and many patients later had to have a limb amputated. Fogarty constructed a hollow catheter with a tiny latex balloon at its tip; his first prototypes used a finger cut from a surgical glove. The other end of the catheter was connected to a bottle of compressed gas, which could be used to inflate the balloon when required. This device (known ever since as a Fogarty catheter) was placed through an incision in a blood vessel and passed through the clot. The balloon was then inflated and withdrawn, dragging the coagulated blood with it. First used in 1961, the Fogarty catheter was a dramatic improvement on earlier methods of clot removal. It not only reduced mortality, but virtually eliminated emergency amputations. Before its introduction, a fifth of patients lost a limb as a result of failed surgery to remove a clot; afterwards the proportion fell to just 3 per cent.30 Despite this triumph, Fogarty had immense difficulty in convincing anybody to take his work seriously. When he tried to publish his findings, the first three medical journals he approached declined to print his paper. In 1962 he moved to the University of Oregon to complete his surgical training, and met Charles Dotter – at last, a clinician whose vision matched his own.
Even among friends, Dotter had a reputation as an untamed maverick. A slim athletic man who spent his spare time climbing mountains, he was a restless bundle of energy at work. One Oregon colleague, the surgeon Albert Starr, said of Dotter, ‘I never saw him normal; he was always in a hypomanic state.’31 Although obviously brilliant – he was appointed professor of radiology at the age of thirty-two, the youngest in the US – Dotter was known as ‘crazy Charlie’, both for his odd manner and his wild ideas. He was evangelical about his work and took his enthusiasm to extremes: on his morning rounds one day in 1961 he gave his students an apparently impromptu talk on the use of the catheter, which he concluded by revealing that he had one in his heart at that very moment, inserted half an hour earlier. To gasps from his audience, he rolled up his sleeve to reveal the end of the instrument, which he then plugged into a monitor in order to demonstrate the pressure readings that could be found in a normal healthy heart.32
The new medical era predicted by Charles Dotter finally began on 16 January 1964. Ten days earlier he had met Laura Shaw, an eighty-two-year-old woman who was admitted to hospital with a badly diseased left leg and foot. Three of her toes were gangrenous, and her lower leg was cold and pulseless, indicating that very little blood was reaching it. An angiogram revealed a large area of obstruction in the femoral artery caused by atherosclerosis. The surgeons strongly recommended amputating the diseased foot but she refused, saying that she would prefer to die. With all other options exhausted, Dotter was given the opportunity to try his new technique. He called it transluminal angioplasty – ‘angioplasty’ meaning the clearing of a blood vessel, and ‘transluminal’ indicating that the treatment takes place through the lumen, the interior channel, of the vessel.
There were three stages to Dotter’s procedure. First a puncture was made in the femoral artery and a guidewire inserted through it, into the vessel and through the area of obstruction. A thin catheter was then slid over the guidewire and also pushed through the atheroma to form a new blood channel. A second, slightly larger, catheter was finally slipped over the first and enlarged the channel still further. This all took a matter of minutes. When Dotter removed the catheter the improvement in his patient’s condition was striking: pulses could be felt in her foot, which returned to a normal temperature. Her pain started to disappear, and in the following week the gangrene receded and the leg ulcer healed, signifying an improvement in its blood supply. Three weeks later an angiogram showed that the previously obstructed artery was now completely clear of atheroma.33 Laura Shaw lived for another three years before dying from unrelated heart disease; until then (as Dotter liked to point out) she stayed on her feet – both of them.
In his first article about transluminal angioplasty, Dotter likened the diseased blood vessels of the leg to a rusty old garden sprinkler. This was in keeping with his therapeutic philosophy; a much-quoted motto of his was ‘If a plumber can do it for pipes, we can do it for blood vessels.’ He also expressed the sentiment in a pencil drawing which he framed and placed over his desk, showing a monkey wrench and length of pipe crossed like swords in a heraldic badge. Obsessed with machinery since his childhood, Dotter certainly liked to see himself as a sort of medic-cum-mechanic, and he constructed many of his catheters himself using whatever materials he had to hand: guitar strings, speedometer cable, or plastic insulation stripped from an electrical cable.34
It is one of medical history’s great missed opportunities that Thomas Fogarty and Charles Dotter, the two visionaries of catheter therapy, were not allowed to work together for any length of time. Fogarty was a surgeon, and his superiors were wary of the peculiar radiologist who liked to tease them that the entire discipline of surgery would soon be obsolete. Though discouraged from having much contact with Dotter, Fogarty did collaborate with him on one notable occasion in 1965. In an attempt to improve his angioplasty method, Dotter tried replacing his usual equipment with a balloon catheter made for him by Fogarty, reasoning that what worked for blood clots might also be a good solution for atheroma. This attempt was successful, but Dotter decided the latex balloon was too flimsy for his purposes and did not use it again.35 Though a one-off, this procedure was of historic significance, the first balloon angioplasty ever attempted. A decade later the technique would become the most powerful weapon in the cardiologist’s armoury.
By 1968 Charles Dotter had published seventeen papers on transluminal angioplasty and performed hundreds of successful procedures. He had also gained an international reputation, but strangely he was more famous in the great surgical centres of Europe than he was in his own home town of Portland. American radiologists mostly ignored his work, still regarding the catheter as a diagnostic tool rather than a therapeutic one. But in Germany, Switzerland and the Netherlands, clinicians had taken up transluminal angioplasty with such enthusiasm that they now called it ‘dottering’.36
In the summer of 1969 Andreas Grüntzig, a thirty-year-old research fellow at the Ratschow Clinic in Darmstadt, had a conversation with a patient that would change the direction of his career. Born in Dresden two months before the outbreak of war, in childhood Grüntzig lost his father – thought to have been murdered by the Nazis – and spent two years living with an uncle in Argentina. He completed his secondary education in Leipzig, but the Communist authorities decreed that he should then begin work as an apprentice stonemason rather than attend university.37 Determined to become a doctor, Grüntzig fled across the border to West Germany in 1959 and began his medical studies in Heidelberg.38 Now, a decade later, he had a particular interest in disease of the peripheral arteries, and found himself chatting to a patient with extensive atherosclerosis. The man was worried by the prospect of complex surgery or toxic drugs, and asked the young doctor whether there was any alternative: was it not possible to brush out the deposits from his arteries, as a plumber would grease from a blocked drain? Grüntzig was impressed by this imaginative suggestion, which prompted him to think about arterial disease in an entirely new way. Not long afterwards he went to a lecture given by Eberhard Zeitler, an eminent specialist in vascular medicine and the leading German disciple of Charles Dotter. Grüntzig was fascinated by the idea of ‘dottering’, and asked his department head for permission to learn more about transluminal angioplasty. The reply was unequivocal: ‘I will never allow this kind of technique to be practised at my hospital.’39
Grüntzig had to wait another two years before he would be permitted to pursue his ambition. After a move to Zurich, where his new boss was far more sympathetic to the idea of catheter-based therapies, he was allowed to visit Zeitler’s clinic to learn the technique. Many of his colleagues remained sceptical, but the unwavering support of one influential member of the surgical department, the pacemaker pioneer Åke Senning, ensured that he was allowed to continue using the Dotter procedure. Over the next couple of years Grüntzig accumulated enough successful cases to show that in the right hands it was a valuable technique. But it was only applicable to a small group of patients, those with accessible lesions in the arteries of the lower extremities, and Grüntzig wanted to treat blockages elsewhere in the body – in particular, those in the coronary arteries. He realised that this would require more sophisticated equipment: the coronary vessels are only a few millimetres in diameter, so simply pushing a probe through the obstruction would not work. Grüntzig knew of Dotter’s use of a Fogarty catheter and felt that the approach was promising; the problem was that the balloon was not strong enough to force an occluded vessel open.
What was needed was a less elastic balloon – something like a fire hose, which when not in use is flattened, but when full of water expands to a maximum diameter determined by the stiffness of its material.40 Armed with a textbook on the chemistry of polymers and a few basic tools, Grüntzig fabricated a series of prototypes at his kitchen table, helped by his assistant Maria Schlumpf and her husband Walter.41 PVC proved a suitable material for the balloons, which were fixed to the catheter with glue, tied with nylon thread, and then hung out to dry on a washing line.42 After hundreds of experiments they found that a sausage-shaped balloon worked best, exerting pressure along its entire length without distortion.
The new catheter was employed clinically for the first time in February 1974, when Grüntzig used it to clear an obstruction from the femoral artery of Fritz Ott, a sixty-seven-year-old who was unable to walk for any distance without debilitating pain. Shortly after treatment his symptoms abated, and he was soon striding long distances with no discomfort.43 The balloon used in this procedure was tiny, measuring just 4 millimetres when inflated, but Grüntzig knew that to use the same approach on the coronary arteries he would have to make one even smaller. It took another year of meticulous experimentation until he had a balloon he was happy with. After successful trials on dogs Grüntzig was eager to move on to patients, but as a matter of courtesy he first explained his plans to his colleagues in the department of surgery. The coronary arteries were traditionally the preserve of the surgeon, and he wanted to make sure that they had no objections to a mere cardiologist invading their territory. Senning’s jovial response was the best he could have hoped for: ‘Herr Grüntzig, you will be taking away my patients, but go ahead!’44
To minimise the risk to his patients, Grüntzig’s first trials took place in an operating theatre, supervised by a surgeon and using a full chest incision. If anything went wrong the surgeon could take over and perform a conventional coronary bypass. The contingency did not arise, however, and after several successful procedures he decided that balloon angioplasty was finally a genuine alternative to surgery. He had to wait several months before a suitable patient was found, but in September 1977 a thirty-eight-year-old insurance salesman, Dölf Bachmann, was admitted to hospital in Zurich with severe angina. X-rays revealed that one of his coronary arteries was blocked a short distance from its junction with the aorta. Given his age and general condition a bypass operation would have been straightforward, but after sharing a hospital room with a patient who was recovering from this procedure Bachmann decided that he would rather avoid the trauma of major surgery.45 He cheerfully accepted the opportunity to be the first to undergo balloon angioplasty. On the afternoon of 16 September Grüntzig himself wheeled his patient into the room where the procedure was to take place – not an operating theatre, but the catheter laboratory, known to its occupants as the ‘cath lab’. At this time of day the nearby operating theatre was not in use, and a cardiac surgeon and anaesthetist were present so that they could perform an emergency bypass if it became necessary.
The atmosphere was not that of the typical operating theatre. People were relaxed, coming in and out of the lab as Grüntzig performed the procedure. There was no blood, and the most glaring anomaly was the patient himself, who was wide awake and chatting to the man who was about to clear his blocked artery. The catheter went into the femoral artery without any difficulty and was soon placed into the left coronary. The only moment of real tension arose as Grüntzig pressed a button to inflate the balloon: nobody quite knew what would happen when it briefly obstructed the blood flow to the myocardium. To everybody’s surprise the heart carried on beating as normal, and Bachmann did not report any discomfort. To make absolutely sure that the blockage had been cleared, Grüntzig inflated the balloon for a second time. When he measured the pressure in the coronary artery he found that the blood flow was back to normal. ‘I started to realise that my dreams had come true,’ Grüntzig later recalled.46 It was a marvellous culmination to a five-year obsession so intense that his daughter Sonja had started referring to the balloon catheter as her ‘twin’.47
Grüntzig named the new technique percutaneous transluminal coronary angioplasty (PTCA): ‘percutaneous’ – meaning ‘through the skin’ – because access to the coronaries is obtained via a needle puncture rather than an open incision. He expected continuing resistance to his ideas, and many experts were unconvinced: after all, placing a balloon inside the coronary artery of a dog was known to cause atherosclerosis.48 Nevertheless, specialists flocked to Zurich to learn the technique – so many of them that they could not be accommodated in the cath lab. Hundreds at a time sat in a large auditorium watching him perform PTCA on a large video screen, the first time that this teaching method (now common practice in medicine) had been used.
Grüntzig’s success should have made him the toast of Zurich, but he was becoming increasingly unhappy with the resources at his disposal: the hospital authorities were slow to appreciate the potential of PTCA. American hospitals had embraced the technique with far more enthusiasm, and in 1980 he accepted an invitation to continue his work in Atlanta. The number of centres carrying out the procedure rapidly increased, and his efforts to prove its worth were finally vindicated four years later when a study of more than 2,000 patients found that over two-thirds were free of all symptoms after a year.49 That was not all: researchers at the University of Göttingen discovered in 1979 that it was possible to use balloon angioplasty to open up the coronary arteries of patients even in the midst of a heart attack.50 This was something even Grüntzig had been reluctant to try, but it was remarkably successful: a study published five years later found that 90 per cent of patients were long-term survivors.51
The explosion in the use of PTCA was truly extraordinary. When Grüntzig left Zurich in 1980 fewer than 900 procedures had been performed worldwide; six years later more than 130,000 had been carried out in the US alone.52 But it wasn’t all good news. As experience accumulated, cardiologists started to notice that many patients suffered relapses. As many as a third of them needed further angioplasty or emergency bypass surgery. Grüntzig was well aware of this problem and worked hard to find a solution. One was eventually found, but he did not live to see it. On 27 October 1985 he was flying back from the Georgia coast with his wife when their plane crashed in a storm, killing them both.53 His loss was a tragic one, for at forty-six he still had much more to contribute; but he had already changed the face of medicine.
A good illustration of the impact of Grüntzig’s work is the fate of his first six patients. One died from heart disease shortly after treatment, and another from an unrelated cancer; but the other four were alive and well twenty years later.54 Dölf Bachmann, the first person to undergo PTCA, was in excellent health and still working in 2015 at the age of seventy-five.55 While angioplasty almost certainly saved his life, he later suffered a recurrence of his condition which was treated by a revolutionary new device that emerged the year after Grüntzig’s death: the stent.
These useful objects are named after Charles Stent, a nineteenth-century dentist who invented a new material for the fabrication of dentures: it was based on gutta-percha, a flexible resin which was also used in golf balls. The word entered surgical parlance when Stent’s compound was used by German surgeons in facial reconstruction operations during the First World War; fifty years later it had come to mean a prosthetic tube made of metal or plastic, used to treat obstructions in internal structures such as the urinary tract.56 Although he did not use the term, Charles Dotter was the first to realise that this concept could also be applied to the blood vessels. In his original description of transluminal angioplasty, published in 1964, he floated the idea of a plastic ‘splint’ which could be inserted into an artery to keep the vessel open.57 In subsequent experiments he found that plastic exposed to the bloodstream promoted clotting, so instead he designed a metal spring that could be slipped over a catheter and delivered to the site of a previous obstruction. When the catheter was withdrawn, the spring remained in place to keep the vessel open.58 This technique was successful in dogs, but making a system suitable for use in humans took another decade. By the early 1980s metal stents were finally being used clinically to open up the larger peripheral arteries, such as those in the leg.
The German cardiologist Ulrich Sigwart was unaware of these developments when he had the idea of doing something similar for the coronary arteries. A contemporary and friend of Andreas Grüntzig, he worked a few hours’ drive from him in Lausanne and was one of the first to be taught PTCA by him in the late 1970s. His first balloon catheters were a gift from the great man himself, handed to him over dinner one evening. These are disposable items nowadays, but at the time they were so scarce that Sigwart had to sterilise and reuse them.59 His first intimation of the shortcomings of angioplasty came in 1981, when one of his patients was rushed into surgery for an emergency bypass operation. Ironically, earlier that day Sigwart had submitted the outline of an academic paper in which he boasted that none of his previous hundred patients had suffered any such setback.60 A number of similar incidents persuaded him of the need to improve the technique.
The problem that he and many others encountered was restenosis – the renewed narrowing of an artery previously opened by the angioplasty balloon. The balloon caused trauma to the wall of the vessel that made its inner layer flake off like badly hung wallpaper. Sigwart hit upon the idea of providing structural support, a sort of internal scaffolding for the vessel. With the help of a local engineer, Hans Wallstén, he developed a prototype. Their first attempt was similar to Dotter’s spring, but this design was soon abandoned in favour of one inspired by the children’s toy known as a Chinese finger trap.61 The device was a tiny tube made from stainless-steel mesh, and – most importantly – was self-expanding. When loaded on to the catheter it was long and thin, but when released it would spring back to its usual, larger, diameter. Hospital administrators were unenthusiastic when Sigwart began animal trials, so much so that he was forced to perform the experiments in a wooden hut in the car park.62 He did not realise at the time that two teams in the US were already working on a similar idea, one of them in collaboration with Andreas Grüntzig.63 But crucially his was the earliest to be ready for clinical use.
Sigwart had to wait several weeks for his first case, but the definitive proof of its efficacy occurred on 12 June 1986, and in dramatic circumstances.fn1 The hospital in Lausanne was full of distinguished cardiologists who had gathered for a course in balloon angioplasty. In the morning they watched, enthralled, as an American specialist, Barry Rutherford, performed a complex procedure on a fifty-six-year-old woman with severe angina. Sigwart was chatting to her afterwards when he noticed her grimace in pain. Instinctively he knew what had happened: the dreaded restenosis. One of the coronary arteries opened by the balloon a short time earlier had collapsed, and little or no blood was passing through it to the myocardium. If she wasn’t already in the grip of a heart attack, she soon would be. Sigwart rushed her back into the cath lab and found that the left coronary artery was, as expected, completely blocked. The obvious solution to the problem was a stent.
The metal tube Sigwart intended to implant in her heart was less than 2 centimetres long, with a diameter of 3.5 millimetres. It had to be placed with pinpoint accuracy in a vessel he would never see with the naked eye. First a guidewire was inserted through the femoral artery into the aorta and then the coronary artery. The stent was crimped on to a balloon catheter which was then threaded over the guidewire and gently guided to its destination, with Sigwart intently following its progress on an X-ray screen. When he was sure it was in the right place he inflated the balloon to expand the stent. There was a brief moment of tension while he scanned the screen anxiously to check that it was firmly in place. He was relieved to see that it was, and the effect was instantaneous: blood flow was restored, and the woman’s symptoms immediately abated. She was the first patient in such a predicament to avoid emergency bypass surgery.64
Sigwart’s illustrious visitors were oblivious to this little piece of history: having seen the earlier procedure to its conclusion they had retired to the cafeteria for lunch. A few months later the woman had to return for stenting of the other affected artery, but she was returned to full health. She and Sigwart kept in touch until her death twenty-eight years later.65 The results of Sigwart’s first nineteen cases were published in 1987 to general incredulity.66 One British cardiologist, Tony Gershlick, recalls his amazement when a colleague returned from a conference and told him that ‘they’re using watchmaker’s springs to keep arteries open’.67 It was soon clear that stenting was far superior to balloon angioplasty. One in ten patients treated using the older technique later required emergency bypass surgery; stents reduced this rate to virtually nil.68 In the late 1980s a further refinement appeared on the scene, a tiny catheter-mounted drill with a diamond-encrusted bit which could be slipped into the coronaries to pulverise the atherosclerotic plaque before the insertion of a stent.69
As ever, the early models were far from perfect. One cardiologist described using them as ‘bungee jumping without checking the knots’: stents fell off the catheter, were swept into the bloodstream, and had to be retrieved from remote parts of the body by an exasperated surgeon. Better designs eliminated this technical fault, but a more serious one remained: a significant proportion of implanted stents quickly became obstructed.70 Researchers found that bare metal caused scar tissue to form on the inside of the vessel, provoking an inflammatory response.
Drugs were the obvious way to prevent this scarring, known as intimal hyperplasia – but how could they be delivered to the coronary arteries? Several possible methods were investigated, but in the early 1990s a number of investigators settled on the same solution: putting them in the stent itself.71 The first drug used for this purpose was sirolimus, derived from a bacterium identified in a soil sample taken from Easter Island twenty years earlier.72 Stents coated with this compound would release it slowly into the bloodstream for a few months, long enough to guard against restenosis. After the disappointments of the previous two decades physicians wanted to be absolutely sure that these devices, known as drug-eluting stents, were really an improvement on what they already had, so they were subjected to numerous clinical trials. The results were strikingly good, with one study finding that they reduced the rate of clinically significant restenosis to zero.73
The invention of the drug-eluting stent has been called the ‘third revolution’ in interventional cardiology – the first two being balloon angioplasty and the stent itself.74 Its success resulted in a long debate – as yet unresolved – about whether it or coronary bypass surgery offer the better long-term results; but for suitable patients stenting is a quick, painless and life-saving treatment which can be performed even in the middle of a heart attack. In the last few years cardiologists have begun to investigate a new type of stent made from magnesium or a special soluble polymer. These devices are bioabsorbable, meaning that in time they dissolve, leaving no trace but a pristine and fully opened vessel.75
What makes this such a momentous development is the sheer scale on which it is used. Percutaneous coronary intervention (PCI) has become a crucial weapon in the battle against heart disease, which remains the leading cause of death in the world. Over a million PCIs are performed in Europe every year,76 around 100,000 of them in the UK,77 making it one of the most frequently used hospital treatments for any condition. But this is not the only way in which interventional cardiology has, to paraphrase Åke Senning, stolen patients from the surgeons.
Andreas Grüntzig’s idea of reaming out blocked coronary arteries with a miniature pipe cleaner was certainly bold, but while he was developing his technique other specialists were working on an even more startling use for the catheter. They hoped to repair hearts distorted by congenital disease, remodelling their internal tissues and removing the need for elaborate surgery. In 1964 William Rashkind, a cardiologist from Philadelphia, proposed a new treatment for cyanotic heart defects, a group of conditions in which a cardiac abnormality results in imperfectly oxygenated blood being circulated throughout the body. His idea was to create an artificial septal defect, a hole between the left and right sides of the heart. This would allow blue, badly oxygenated blood to travel back into the pulmonary circulation, giving it a second opportunity to pass through the lungs before being pumped to the rest of the body. Conceptually this was similar to the Blalock–Taussig shunt, invented two decades earlier to alleviate tetralogy of Fallot, and when Rashkind outlined his idea at a conference one of the first to appreciate its merits was one of the pioneers after whom the operation was named. Helen Taussig wrote to him afterwards, saying: ‘It would be wonderful if we can do some of the simpler operations without opening up the chest. I think that is a real advance and a real look into the future.’78
Rashkind entered this brave new world two years later, when he treated a newborn infant with transposition of the great arteries (TGA), in which the positions of the aorta and pulmonary artery are swapped. This creates two independent circulations, one pumping blood endlessly through the lungs, while the body receives only useless deoxygenated blood. Babies born with the condition are cyanotic from lack of oxygen, and unless there is some way for blood to find its way from the systemic circuit into the pulmonary one they rapidly die. Rashkind’s patient was only hours old when he inserted a catheter into the right side of its heart and manipulated it into the foramen ovale, the small window between the two atria which usually closes shortly after birth. He then inflated a balloon at the catheter tip and withdrew it sharply to tear a larger, permanent hole in the septum.79 This was not a cure, but like the Blalock–Taussig operation it was an effective, life-saving measure which hugely improved the patient’s condition. A journalist from Time magazine was allowed to watch one of these early procedures being performed on Bobby Weiner, a sixteen-day-old with TGA, and noted the remarkable change in his skin colour from slate-grey to pink when the balloon was withdrawn. The baby required only a local anaesthetic and sucked on a dummy as the operation took place.80
Rashkind continued to investigate other ways of treating congenital disease, and in the late 1970s he developed an alternative method of creating a septal defect. Instead of a balloon, the catheter contained a tiny blade just 12 millimetres long and 1 millimetre wide. As it passed through the blood vessels the blade was retracted, like that of a folded penknife; but when it reached the inside of the heart the operator could turn a lever to expose it, and make an opening between the left and right atria.81
Of course, a hole in the heart is only desirable for those with other rare defects; for most people born with otherwise normal cardiac anatomy they can be inconvenient or even life-threatening. Devices for closing atrial or ventricular septal defects via the catheter also started to appear, the first invented by Terry King, a cardiologist from New Orleans. When as a young man he first suggested repairing holes in the heart without surgery, the idea seemed so outlandish that one colleague told him to see a psychiatrist.82 Brushing off this helpful advice, he and a colleague, the surgeon Noel Mills, spent several years designing a catheter system containing two tiny umbrellas. These were furled as the catheter entered the heart chambers, but when it had passed through the defect they were opened, one on each side of the hole. The two umbrellas then snapped together, forming an artificial barrier over which new tissue would grow.83 Their first patient, seventeen-year-old Suzette Creppel, received umbrella closure of an ASD in April 1975, made a full recovery and is still alive today.
The scope of catheter interventions to operate inside the heart widened still further in 1981, when Jean Kan, a successor of Helen Taussig as head of paediatric cardiology at Johns Hopkins Hospital in Baltimore, developed a successful method of treating narrowed valves.fn2 Inspired by a talk given by the visiting Andreas Grüntzig, she decided that inflating a balloon inside the valve could be a means of correcting pulmonary stenosis.84 After two years of animal experimentation she performed the first successful procedure on Sharon Owens, aged eight; in her patient’s honour, Kan called the device the Owens Pulmonary Valvuloplasty Balloon, the name by which it was known for some years afterwards.85 Variations of the Owens balloon were subsequently used to treat the other valves of the heart, beginning with mitral stenosis in 1984.86
By the end of the decade, cardiologists had a formidable array of techniques at their disposal to tackle complex congenital conditions without once picking up a scalpel. Many of these patients were children, and in addition to avoiding the trauma and long recovery associated with an operation, catheter treatment spared them the disfiguring scar which is a permanent reminder of open-chest surgery.
Better still, the catheter provided a treatment for an entire class of illnesses that were almost impossible to treat surgically. Arrhythmias, disorders of the heart rhythm, had long been among the most difficult conditions for physicians to treat, because the mechanisms behind them are so complex. When a surgeon repairs a damaged valve or corrects a congenital malformation, the cause of the problem is usually visible to the naked eye, and fixing it is a matter of cutting or stitching the structures concerned. The causes of many arrhythmias, on the other hand, are invisible even when the organ has been cut open: the heart of a seriously ill patient may look completely normal. That is because the nature of the problem is electrical, and the faulty structures are the microscopic conduction pathways that carry electrical impulses from one part of the heart muscle to another.
On 19 October 2003 the British prime minister Tony Blair was spending the weekend at his official country residence, Chequers, when his heart began to race for no apparent reason. This was not the first time he had experienced the phenomenon, which he had previously attributed to drinking too much coffee. When the palpitations failed to subside he went to the local hospital, where he was told he needed urgent treatment from a specialist in London.87 News that the premier had been rushed to a cardiac unit caused some panic, but the condition was easily treated. At the Hammersmith Hospital he was diagnosed with supraventricular tachycardia, an arrhythmia which causes the heart rate to increase to over 180 beats per minute. Episodes of SVT are uncomfortable but rarely life-threatening, although over a long period they can cause serious complications. The cause of the palpitations was an abnormal conduction pathway inside the heart, so that parts of the myocardium were receiving an electrical stimulus far more frequently than they should. After a recurrence of his symptoms the following year, Blair returned to hospital for a brief procedure which banished his symptoms for good. Known as radiofrequency ablation, it uses a catheter with a special tip to destroy the tissue responsible for the aberrant electrical signals. Had any of his predecessors been hospitalised with SVT, it is doubtful whether they could have stayed in office: although drugs can sometimes control the condition, it remained incurable until the late 1980s.
The technique of radiofrequency ablation was an innovation that came out of one of the younger branches of medicine: cardiac electrophysiology, the study of the electrical activity of the heart. The discipline was established in the 1960s, as researchers started to unravel the mechanisms responsible for the many different types of arrhythmia, identifying and mapping the specific electrical pathways that caused the organ to misfire. One of the leading lights of this new field was the Dutch cardiologist Hein Wellens – later known as the ‘giant of Maastricht’ for the importance of his contribution88 – who decided to study Wolff–Parkinson–White syndrome, a condition which causes an abnormally fast heartbeat. Colleagues of Wellens in Amsterdam had recently discovered that the hearts of patients with WPW syndrome contain an extra conduction route between the atria and ventricles: impulses passing through this so-called accessory pathway can cause the ventricles to contract prematurely, resulting in tachycardia.
Wellens showed that it was possible to deliberately induce and then terminate episodes of arrhythmia by passing an electrode mounted on a catheter into the heart chambers and stimulating the areas responsible with an electrical current.89 This led to the first surgical treatment for the condition the following year, when surgeons at Duke Hospital in North Carolina operated on a thirty-two-year-old fisherman who had suffered attacks of tachycardia since the age of four, leading eventually to heart failure. After using ECG electrodes to pin down the exact location of the accessory pathway, surgeons opened the heart and made a 6-centimetre incision in the interior wall of the right atrium, severing the connection and curing his condition permanently.90
In the following decade this procedure was used to treat a variety of life-threatening arrhythmias, sometimes using cryoablation (extreme cold) to freeze the rogue pathways until they stopped working. But cutting open an otherwise healthy heart to do so seemed an unnecessarily invasive procedure, and using the catheter instead was one obvious way to avoid opening the chest. In the late 1970s a cardiologist in San Francisco, Melvin Scheinman, began a series of animal experiments using high-voltage electricity to burn (ablate) areas of tissue inside the cardiac chambers. The method he eventually adopted used a powerful DC current generated by a defibrillator and passed down a wire inside a catheter into the heart.91
While he had some success employing this approach on patients, there were major problems with the technique: it was safer than surgery, but the risks were terrifying. When an ablation went wrong it could make the arrhythmia worse, damage the coronary arteries or even perforate the heart.92 The answer was not some dramatic technological breakthrough, but a piece of equipment that had been in operating theatres for over sixty years. In 1925 an eccentric plant physiologist in Boston, William Bovie, became interested in the idea of using electricity to perform surgery. He invented an apparatus that produced a precisely modulated current which, when passed through a needle-like electrode, would cut through flesh as easily as a scalpel. By changing the nature of the current it was also possible to dehydrate the tissue, or to arrest bleeding by coagulating the blood. The secret of this versatile device was that it used a particular type of high-frequency alternating current (AC). Most domestic mains power is AC, and typically the current flips direction fifty or sixty times per second. Bovie’s equipment produced an electric current that alternated as many as three million times per second, the frequency of radio waves.93 He demonstrated his invention to the brain surgeon Harvey Cushing, who was so impressed that he used it to operate on a number of patients with tumours he had previously thought inoperable. The results were stunning: as a contemporary press report noted, ‘In several of the operations … the patients were insane before they went under the electric knife, and came out sane again.’94
Bovie’s ‘electric scalpel’ – commonly but inaccurately known as the diathermy knife* – became a staple of the surgeon’s toolbox, and in 1987 the German cardiologist Thomas Budde introduced the device to the cath lab when he treated a forty-nine-year-old woman with persistent tachycardia.† Drugs and two previous ablations using DC current had proved totally ineffective in controlling the condition, and the patient was prone to regular fainting fits. A catheter was manipulated into her right atrium, and five pulses of radiofrequency current passed through the electrode at its tip, finally liberating her from the palpitations which had caused her so much discomfort and left her at risk of a stroke and other serious complications.95
Radiofrequency ablation was far superior to anything before it: it allowed cardiologists to zap the tiny region that was causing an arrhythmia without doing any damage to surrounding structures. Occasionally the burnt tissue would heal, causing a recurrence of symptoms and necessitating a repeat procedure, but this was rare: in one study, researchers found that 98 per cent of patients were cured at the first attempt.96 In the early years of the procedure, when it was difficult to pinpoint the area causing a problem, ablation often resulted in the total destruction of the heart’s conduction system, so that patients needed a pacemaker to maintain a normal heartbeat. Today’s technology is far more sophisticated, often allowing cardiologists to make a precision strike on any unwanted conduction pathways while leaving the rest untouched. While pacemakers remain the usual treatment for most bradycardias (abnormally slow heartbeats), ablation can now be used to treat a wide range of tachycardias, including atrial fibrillation.
In some ways, ablation is the most remarkable of all the many victories won against disease of the heart. Here’s a sobering fact: in over a century of evolution, heart surgery has rarely cured a patient. The majority of procedures documented in this book, from the Blue Baby operation to transplantation, valve replacement to stenting, are merely palliative. They may offer relief from symptoms, but they do not cure the underlying condition. Radiofrequency ablation offers a definitive cure for an entire class of patients whose condition was previously beyond the capabilities of medicine. Andrew Grace, an electrophysiologist at Papworth Hospital, was one of the first British specialists to adopt the technique. He recalls the dreadful outlook for patients with serious arrhythmias when he was a newly qualified doctor in the early 1980s: ‘I used to think that Wolff–Parkinson–White syndrome was one of the worst things that could happen to a young person. I remember these patients aged eighteen who were on three different anti-arrhythmic drugs surrounded by men much older than them having heart attacks. It was as bad as having cystic fibrosis or something, and now—’ he clicks his fingers ‘—we can fix them in an hour.’97
It is more than half a century since Charles Dotter told an incredulous audience that the humble catheter would one day become ‘an important surgical instrument’. Subsequent developments have surely exceeded even his expectations: while we haven’t quite reached the world of Fantastic Voyage, with microscopic submarines navigating the blood vessels, interventional cardiologists now routinely repair congenital abnormalities, treat heart attacks and cure life-threatening arrhythmias – all without lifting a scalpel. The rise of the discipline was so meteoric that some cardiac surgeons began to fear that their own skills would soon become obsolete. That’s one prediction that hasn’t (yet) come true, but interventional cardiology continues to innovate at a pace not seen in heart surgery since its heyday in the 1960s. And as we’ll see in the next chapter, the latest developments have seen surgeons and interventional cardiologists working together more closely than ever before.