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 Table of Contents  
Year : 2017  |  Volume : 3  |  Issue : 1  |  Page : 44-52

Coronary angioplasty: Back to the future

1 Department of Cardiology, Consultant Cardiologist, Care Hospital, Hi-Tech City, Hyderabad, India
2 Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, K.R. Hospital Campus, Mysore, Karnataka, India

Date of Web Publication17-Jul-2017

Correspondence Address:
Nilkanth Chandrakant Patil
Metro Hospital and Heart Institute, X-1, Secotor 12, Noida, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcs.jpcs_1_17

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Puel and Sigwart, in 1986, deployed the first coronary stent to act as a scaffold preventing vessel closure reducing the incidence of angiographic restenosis. The first stents were bare metal stents. The first drug-eluting stents to be approved were coated with paclitaxel or sirolimus. Since these stents came with a lot of promise but also with risk of thrombosis, the next step was biodegradable stents. These stents are expected to degrade into nontoxic byproducts. They came with a lot of fanfare but are now being viewed with caution because of initial poor results. We do not know what the future holds.

Keywords: Coronary angiography, coronary angioplasty, history of cardiology

How to cite this article:
Patil NC, Nanjappa V. Coronary angioplasty: Back to the future. J Pract Cardiovasc Sci 2017;3:44-52

How to cite this URL:
Patil NC, Nanjappa V. Coronary angioplasty: Back to the future. J Pract Cardiovasc Sci [serial online] 2017 [cited 2022 Dec 5];3:44-52. Available from: https://www.j-pcs.org/text.asp?2017/3/1/44/210853

  Introduction Top

History is an amalgamation of the trials, tribulations, sacrifices, the indomitable spirit of human minds, the failures, lessons learned from the failures and like the phoenix it needs to rise to tell the tale for generations to gladly reminisce the part they played and to the younger generations to show the roots of science which has evolved and bow down with respect and fathom the courage to carry on the baton of science with vigor, sincerity, and inquisitiveness. What future shall unfold, only time can tell, but its quintessential to keep the spirit of questioning and seeking answers alive like that of “Why why girl of Mahaswetha Devi's children's book.”

Indian documentation of description of heart dates back to 600 BC in Charaka Sanhita and Sushruta Sanhita. Here, heart was described as the seat of consciousness and as a prime mover of “Prana” or impervious energy. The heart being the center of the system, transmits energy through different “Nadis” or channels, which were later on described as “Siras” or veins, “Dhamanis” or arteries, and “Srotas” or flow.

William Harvey, a British physician's discovery which was published in 1628, De Motu Cordis, where he stated: “It has been shown by reason and experiment that by the beat of the ventricles blood flows through the lungs and it is pumped to the whole body. There it passes through pores in the flesh into the veins through which it returns from the periphery… finally coming to the vena cava and right auricle…. This is the only reason for the motion and beat of the heart.”[1] This concept is considered as renaissance in cardiology and close to three centuries later, cardiology, especially interventional cardiology witnessed a series of grand achievements with capsulated nuggets of stories within. In this review, we will summarize few important events of historical significance that made coronary angioplasty possible the way we do it today [Table 1].
Table 1: A Cournand and R Dickinson.

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  1929–1959: Early Human Cardiac Catheterization (Werner Forssmann, Dickinson Richards and Andre F Cournand) Top

The first catheterization of the living human heart was performed by a young surgeon, Werner Forssmann [Figure 1]a, (on himself!) in 1929 in Eberswalde, Germany.[2] Forssmann was born in Berlin and obtained his medical degree in 1929. Dr. Forssmann's inspiration to perform what is now called cardiac catheterization came from a sketch in his physiology textbook depicting the Stephen hales method of measuring blood pressure by inserting a long, thin tube into a horse's carotid arteries, and measuring the height to which the column of blood rose.[3] Chauveau, Marey, and Bernard (f1–f40) had earlier measured the intracardiac pressures of horses and other animals by inserting catheters directly into the heart. Fascinated by those experiments, Dr. Forssmann proposed to reach the heart of man, not through the jugular, but through the veins in the arm. Before 1929, it was believed that a catheter would get entangled in the heart chambers causing it to stop beating and lead to death. However, Dr. Forssmann believed that it may be possible to reach the human heart safely by catheterization, and it would be an excellent route to administer drugs for therapeutic purposes.
Figure 1: (a) Stephen hales measuring blood pressure. (b) Frossmann's self-catheterization

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In 1929, while working in Eberswalde, just after his graduation, he persuaded his idea of human cardiac catheterization. Initially, he collaborated with his colleague Peter Romeis and tried inserting a urethral catheter in his heart, however, Romeis thought it to be too dangerous and they broke up the first attempt.[4]

As he puts it in his autobiography, “I decided to override Schneider's prohibition and go ahead with the experiment on my own heart. I needed an assistant, the surgical nurse. I had to win her over or I would have no access to the necessary sterile instruments. The following afternoon the good lady was sitting in her cubicle when I breezed in whistling cheerfully. 'Nurse Gerta, I want you to give me a set of instruments for a venesection under local anesthesia and a urethral catheter.' 'She started up suspiciously.' 'But no one in the wards is scheduled for a venesection. You're not planning to do that experiment of yours against boss's orders, are you?' 'Nurse Gerta, you need to know nothing about what I am going to do but supposing I were to do the experiment—it would be safe.'” “She eyed me closely. 'Are you absolutely sure there is no danger?' 'Absolutely' 'All right then, do it to me. I put myself in your hands.' 'Well, why not? You'll be the first person in history to undergo such an experiment.'” Forssmann states that he had no intention of going through with the experiment on nurse Gerta, but he did proceed to have her lie down on the operating table and strapped her arms and legs to the table. He then proceeded to anesthetize his own arm while distracting her by applying iodine to her elbow. He describes how, with one hand, he somehow made an incision over his own antecubital vein, opened the vein, and inserted a urethral catheter about a foot into the vein. Releasing nurse Gerta, he said, “There we are. It is ready now. Call the X-ray nurse.” They walked some distance to the X-ray department on the floor below where under the guidance of a fluoroscope he advanced the catheter the full 60 cm into his right ventricular cavity. This was then recorded on X-ray film showing the catheter lying in his right atrium.[4]

The rest is history; and like everything in history, which was before time and thoughts, he had to face disciplinary action and was forced to quit cardiology and take up urology instead. His contribution and dare-devilry won him a Nobel Prize in 1956 along with Cournand and Richards but not erstwhile working for Nazi and being captured in a US prisoner of war camp [Figure 1].

Though his work was not recognized by his fellow medical community in Germany, Dickinson Richards, and Andre Frederic Cournand continued on from where Forssmann left. They continued their work in Columbia University and Bellevue Hospital in New York, developed, safe, practical approaches to catheterization of the heart, began the systematic exploration of normal and abnormal hemodynamics. They recorded intracardiac pressures and cardiac output in normal subjects and in patients with many forms of congenital and acquired heart disease.[5]

Forssmann, Cournand, and Richards were collectively awarded the Nobel Prize. In his acceptance speech of the Nobel Prize, Cournand stated that “the cardiac catheter was… the key in the lock.” By that time Forssmann had already moved on to urology and was practicing in a small community hospital, and when he received the call that he was awarded the noble prize in 1956, his first response was “for what?” [Figure 1]b.

Although A Cournand and R Dickinson described human catheterization of the right heart through the venous system, it was Zimmerman, who first described left heart catheterization through the ulnar artery in patients of syphilitic aortic regurgitation in 1950 [Figure 2].[6]
Figure 2: (a) Stephen hales measuring blood pressure. (b) Frossmann's self-catheterization.

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In 1953, Seldinger introduced the technique of percutaneous entry which is the premise for all interventions.[7] In 1959 Ross J, Braunwald E and Morrow AG did the first transseptal catheterization of the human heart.[8]

  1958–1964: First Selective Coronary Angiography – An Act of Serendipity (Dr. Mason Sones) Top

The technique of right and left heart catheterization helped in diagnosing valve disorders and studying cardiac physiology. However, its application in the treatment of coronary arteries was limited as it was not possible to accurately define the anatomy. Various indirect and dangerous methods were tried to define the coronary anatomy including but not limited to, the following methods before Mason Sones experiment (inadvertent!) of selective coronary angiography.

Earliest angiocardiographic techniques were dependent on the injection of a large amount of contrast agent into a peripheral vein, which rarely produced enough opacification of coronary arteries to make any diagnosis. Later, cardiac ventriculography was tried which involved the injection of contrast through a needle inserted through the chest wall, pleural space, pericardium, right ventricular myocardium, and interventricular septum, which caused arrhythmias and the opacified vessels were partially obscured by the opacified left ventricle.[9] Thoracic orthography failed to produce recognizable opacification in 30% of the aortograms, and in about half the cases only one coronary vessel was visualized.[10] In 1958, Dotter demonstrated occlusion aortography in canine experiments using soft double-lumen balloon catheter which opacified the coronaries.[10] There was one lumen at the tip and another an inch proximal to it. On inflation of the balloon, it occluded the aorta and contrast injection opacified nonselectively the coronaries from the distal lumen. He reported this method in 78 dogs that survived the procedure and produced good images of coronary arteries. In this method, he used acetylcholine to cause transient cardiac arrest, which markedly improved the quality of the images. However, there was significant risk of ventricular fibrillation, and hence, it never became popular.

It was believed at that time that if you inject a dye into the coronary arteries, it would result in asymmetrical hypoxia of the coronary circulation, creating electrical imbalance and fatal ventricular arrhythmia and would invariably result in death as closed chest defibrillation was still not known. Andre Cournand personal experience supported that hypothesis. He had tried selective coronary angiograms by injecting contrast media in coronaries directly, in dogs and had found that it had almost 100% fatality rate.[11]

Then came the historic day of October 30, 1958, at the Cleveland Clinic, where Dr. M Sones was performing a catheterization study of a 26-year-old man who was diagnosed with rheumatic heart disease with mitral and aortic valve disease.[12] Initially, Sones performed an left ventricular angiogram and then proceeded to perform an aortic root angiogram by placing a side-hole catheter (The National Institutes of Health) in the patient just above the aortic valve. He ordered to inject 50 ml of contrast injection, but as the injection began, he noticed that the catheter whiplashed into the right coronary artery, and most of the contrast was delivered into the right coronary artery. Fearing that the patient would go into incessant electrical storm Sones leaped up to the table with a scalpel to open his chest for an open cardiac massage as the closed chest compression and cardiopulmonary resuscitation (CPR) was not still known. But as everybody looked at oscilloscope (electrocardiogram monitor), they saw that the patient has prolonged asystole and bradycardia. The patient was still conscious and responsive. Hence, Sones ordered him to cough vigorously, and along with atropine injection, normal sinus rhythm was restored and the patient recovered within a minute.[12] The result was the first selective coronary angiogram. This event marked the beginning of the new era of selective coronary angiogram, which revolutionized the diagnosis and management of coronary diseases. Sones described this event as an inadvertent accident.

Sones had been performing serial injections of 20 cc contrast media with catheter tip kept selectively in different aortic sinuses to ensure enough coronary filling by dye lasting for enough cardiac cycles to be captured in images. The resulting arteriogram was considered to be adequate in more than 90% of cases and ventricular arrhythmias, which had been feared as a consequence of transient asymmetrical myocardial hypoxia with this method of delivery, failed to materialize.[11],[12],[13] He believed that the human coronary circulation was not the same as the canines, and the fatal ventricular arrhythmia would not invariably occur. He reported this event realizing its potential for the future of cardiology. Dotter sent his student Judkins to train under Sones for selective angiography. Judkins having had the best of both worlds came up with improved sets of catheters for selective coronary angiography. M Sones and Melvin Judkins taught the procedure to the physicians and radiologists and made it more popular [Figure 3].
Figure 3: (a) Mason Sones performing angiograms, (b) Sones first inadvertent first selective CAG.

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  1964–1978: First Percutaneous Angioplasty – Peripheral and Coronary (Charles Dotter and Andreas Gruentzig) Top

Charles Dotter: The father of intervention

There is a saying “the best way to predict future is to create it;” one man called Charles Theodore Dotter seems to have believed in it more than anybody else. He is credited with developing a new medical specialty, interventional radiology. The main goal of Dotter was to treat patients without the scalpel, and this he ensured by inventing intravascular catheters and interventional devices including various Teflon catheters, flow-directed balloon catheters, double-lumen balloon catheter, safety guidewires, catheter-directed thrombolysis and invented loop-snare catheter for retrieving foreign bodies, developed tissue adhesives for vascular occlusion, and the “J” tipped guidewires.

He found scientific use in mundane objects such as the guitar strings, vinyl insulation stripped from intercom cables, and speedometer cables. When Cath lab technicians of today ready the materials for use, his technicians in the lab made the materials for use. He envisioned an age of no scalpel, to reduce mortality and morbidity. He was way ahead of his time in his thoughts, implementing those thoughts, and giving shape to them as concrete ideas. It took more than 20 years for other interventionists to understand things that he not only postulated but also performed. Dotter's favorite conceptual trademark was a “crossed pipe and wrench.” It was Dotter, who made it possible for cineangiograms to be taken, till then every angiographic shot had to be developed in the dark room for interpretation. He believed if a plumber can do (to) pipes why cannot a physician do the same for a vessel (repair a vessel).[14]

Percutaneous transluminal angioplasty was his landmark contribution. He also introduced the concept of percutaneous arterial stenting and stent grafting by placing the first percutaneous “coil-spring graft” in the femoral artery of a dog. Dotter's first arterial recanalization was quite inadvertent; in 1963, he accidentally recanalized an occluded right iliac artery by passing a percutaneously introduced catheter retrogradely through the occlusion to perform an abdominal aortogram in a patient with renal artery stenosis.[14]

1964 was the time when Dotter and his trainee Melvin Judkins did their first percutaneous transluminal angioplasty.[14],[15] It was his patient Laura Shaw, an 82-year-old woman who was admitted with nonhealing ulcer and gangrenous toes and was unwilling for an amputation, which was the standard treatment in those times. Dotter found out that Ms. Shaw had short-segmental stenosis of the superficial femoral artery, an ideal lesion on which to test his percutaneous “dilating” catheters. The procedure went well, and within minutes, the patient's foot was warm and hyperemic. Her pain disappeared within a week, and the ulcer soon healed. Follow-up angiograms done 3 weeks and 6 months after Dotter's intervention showed the vessel to be patent. Ms, Shaw died of congestive heart failure almost 3 years later walking on her own feet.

Dotter initially had an adverse relationship with surgeons. A surgeon from the community sent Dotter a patient for an angiogram of the left superficial femoral artery. The surgeon asked for a left femoral angiogram and boldly wrote on the form “visualize, but do not try to fix.” The diagnostic angiogram showed that both the superficial and deep femoral arteries had areas of stenosis. Dotter dilated the deep femoral artery. He pointed to his students how “(it) only took a moment” to dilate the stenosis. In this patient, the planned open superior femoral arterioplasty procedure eventually failed, while the interventional dilation of the deep femoral remained open even at 5 years follow-up which saved the man's leg [Figure 4].[14]
Figure 4: (a) Charles Dotter and angioprahphy of his first patient, (b) Laura Shaw: (A) before transluminal dilation of the left superficial femoral artery, (B) immediately after dilation, and (C) 3 weeks after the procedure.

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Dotter's beliefs and eccentricity are narrated in an interesting snippet wherein he was talking about cardiac physiology and pressure tracings in the grand rounds all the while having a catheter in his heart. He rolled up his sleeve, and there was the end of the catheter sticking out of his vein, and he said, “Now I'll show you what a normal heart reading looks like.” Hence, he went and plugged himself into the oscillograph machine with all his students gasping in horror. There he was, a man standing there with a catheter in his heart—and he moved it among the chambers of the heart as he stood there, and he explained what the graphs represented. It was an absolutely horrifying example, but it was the kind of thing he did, to say it is perfectly safe, it can be done, and it is not dangerous.[14]

Few of other Dotters ideas were one of a “specialized balloon inside the heart which intermittently inflated…” later evolved into intra-aortic balloon pump. He also recognized the efforts it takes for a prolonged CPR and used a mechanical device called circulator (electric motor, cam, and thrusting rod with rubber shoes over patient's sternum for compression); however, it never came into practice, and the idea is still perceived into making of mechanical CPR machines.

The man who made all this possible was a mountaineer, painter, and moreover, a family man with novel ideas which his run mill mind churned and to which he gave shape despite the health odds of Hodgkins lymphoma and coronary artery surgeries twice. He was frequently called as “crazy Charlie” for his out of the box ideas and inventions.

In today's world where we have organized education system which kills the why's at a budding level, here was a man who respected his ideas enough to execute them and not bother the criticism which came along as he always believed in himself, and the basis for most of his work was to effectively treat patients in a simplified way. Although Dotter had more than 300 publications in his name, but lack of controlled trials, and professional skepticism at his unusual and bizarre ways, it took another few years (and Andreas Gruentzig) before it became widely accepted in practice.

Andreas Gruentzig: The father of interventional cardiology

Andreas Roland Gruentzig was born at the start of the World War II on June 25, 1939, in Dresden, Germany. Gruentzig studied medicine at Heidelberg University graduating in 1964. He became interested in vascular interventions after hearing a lecture on angioplasty by Charles Dotter's in Frankfurt. Because of bureaucratic resistance in Germany about newer medical procedures, he migrated to Zurich to further pursue the subject of angioplasty.[16]

He considered the advantage of adding an inflatable component to the catheter (described by Dotter). He began developing trial versions of this balloon catheter in his own kitchen, searching for possible options for the material and design. By 1975, he had developed a double-lumen catheter (a single-catheter tube with two separate channels - the over the wire balloon of current cardiology practice) fitted with a polyvinylchloride balloon - it was this balloon, first developed at his kitchen table, that would set in motion a revolution in interventional cardiology.

The story itself as to how he invented the coronary balloon catheter is interesting. Gruentzig had heard of the ideas of Porstmann, who placed a latex balloon in a slotted angiographic catheter, and the balloon idea was attractive to him. He needed a small-bore catheter with a distensible segment, but the available balloon material only expanded around the lesion and did not provide the force necessary to open it. Gruentzig worked evenings in his kitchen with his assistant, Maria Schlumpf, her husband, Walter, and Michaela, Andreas' wife, and during those sessions, many versions of the balloon catheter were designed and built with tiny bits of rubber, thread, and epoxy glue. The problem was always the same: When distended in a constriction, the balloon always took on an hourglass appearance without opening the lesion. The concept evolved to use a sausage-shaped distensible segment that would not expand over a predetermined size and would accommodate high pressure. The only catheters available were of single lumen. He devised a method by which the peripheral venous catheter (PVC) tube with the distensible segment was pulled over an angiographic catheter. The lumen of the angiographic catheter would accommodate the guide wire and allow contrast material to be injected for localization, whereas the space between the catheter and the PVC tubing would be used to inflate the balloon. Schmidt, a young man helped construct a longitudinal groove on the angiography catheter's outer surface. This was a great step forward. Then, long PVC tubing with the distensible balloon segment at the end was slipped over this angiography catheter and fixed at the proximal and distal ends. Y connector was then developed, and the double lumen catheter was ready for use after a year of tinkering job and most of this great work took place in the kitchen.[16]

He initially worked on animals and presented his experiments in the American Heart Association meeting in 1976 telling the audience that he would soon take his method into the human heart. Most of those listening were skeptical, however, Dr Richard Myler of Saint Mary's Hospital in San Francisco was one, who saw the potential. He invited Andréas to join him and together; they collaborated to perform the first in human percutaneous coronary angioplasty during bypass in San Francisco.[17],[18]

The first human patient he selected was a patient with left main coronary artery and multivessel disease and he was not able to get access as he had peripheral vascular disease and the only available access he could get was left brachial route but he could not selectively engage the catheters with the available catheters as well, and hence, the procedure was abandoned. He later surmised that “if you start a method, you should start with an ideal case and not with end-stage disease and this has been the truth for so many of us being in a similar position later in time.”

On September 16, 1977, in Zurich Switzerland, Gruentzig performed the first coronary angioplasty on an awake human. The patient, Adolph Bachman, a 38-year-old man suffering from angina, single-vessel stenosis, remained conscious throughout the procedure. The procedure was performed on that day. Andreas later remembered: “Early in the afternoon at a time when the anesthesiologist and the cardiac surgeon were available and no cardiac procedure was under way in the operating room, the patient came in to our catheterization laboratory and was catheterized in the usual fashion.” The guiding catheter was placed in the left coronary orifice, and the dilatation catheter was inserted. The left femoral artery was also punctured, and a sheath was placed. This was done to have arterial blood available to pump in through a roller pump through the main lumen of the dilatation catheter into the coronary artery to perfuse the myocardium during balloon inflation. The catheter wedged the stenosis so that there was no antegrade flow, and the distal coronary pressure was very low. To the surprise of all of us, no ST elevation, ventricular fibrillation, or even extrasystole occurred, and the patient had no chest pain. At this moment, I decided not to start the coronary perfusion with the roller pump. After the first balloon deflation, the distal coronary pressure rose nicely. Encouraged by this positive response, I inflated the balloon a second time to relieve the residual gradient. Everyone was surprised about the ease of the procedure and I started to realize that my dreams had come true. A few hours after the procedure, the patient phoned a newspaper without my knowledge and wanted to release his story. The reporter came to him but also asked me for further details and I begged him not to destroy me and the method by early advertisement of a procedure which had not proven to be effective at that point in time. I asked him to wait until more experience would have been accumulated. The patient remained free of angina and the artery remained open without restenosis when I recatheterized him at Emory on September 16, 1987. Dr. Gruentzig had done 3 more procedures by the next American Heart Association meeting. After his presentation of the first four cases of coronary angioplasty in that meeting (along with Dr. Richard Myler), Dr. Sones Mason, came to Dr. Myler, crying, embracing him, and saying, “It's a dream come true!”[16]

The hall of fame not only includes Gruentzig's picture but also that of the patient who underwent the first angioplasty and continues to be a quizzer in cardiology forums. The credit for making the medical world accept the technique goes to him which was a continuous, careful, and rigorous process of live demonstrations [Figure 5].[19]
Figure 5: (a) Andreas Gruentzig and angiograms of the first patient to undergo successful angioplasty. (b) Top, diagnostic angiogram (September 14, 1977) and appearance at the time of angioplasty (September 16, 1977). Bottom, The 1-month restudy. (October 20, 1977) and the 10-year repeat study. (September 16, 1987).

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Gruentzig's work used the premises of Dotter's work and he credited Dotter for the same. Andreas was a very aggressive person in formulating his ideas but very conservative in approach, explaining the complications in detail. He understood that though the procedure was lifesaving it had the potential to cause complications if not done properly and may deter from physicians accepting it for their patients. He took a great interest in teaching other fellow in the art of angioplasty. He organized multiple training courses for teaching angioplasty. His main focus was always on patient safety. This attitude of his has a major role in advancing angioplasty and its acceptance in the physician community.[19]

1985 was a year of loss in the history of Interventional medicine: Dotter, Sones, Judkins and Gruentzig all passed away within 9 months of each other.

  1979: Expansion of Angioplasty (Plain Old Balloon Angioplasty) Top

Dr. Geoffrey Hartzler performed the first coronary angioplasty at the Mayo Clinic in 1979. Dr. Gregg stone in one of his interviews had to say this regarding Hartzler. “Whereas Andreas believed percutaneous transluminal coronary angioplasty (PTCA) should be restricted to proximal focal lesions, Geoff was the pioneer who brought interventional cardiology (balloons only, no less) to patients with acute myocardial infarction (MI), multivessel and left main disease, chronic total occlusions, and much more.”[20],[21] He established a database of interventional cases, and this helped bring evidence-based medicine to the field. Hartzler pioneered advanced pacing and mapping of cardiac arrhythmias and performed work and research that was seminal in the growth of the field. In all of these things, his work, his approach, and his life could be summarized by passion, by creativity, by sharing, by educating, and by taking care of patients, again reminding us technological know-how should be and must be fuelled by kindness and compassion, the basic premise of being a doctor.

  1986–2011: Stent and Stenting Top

In 1986, when the world was being stormed by advent of E-mails making postal letters obsolete, so was another invention taking place in interventional cardiology of the usage of stents. It continues to be a matter of debate regarding the origin of the word “Stent,” whether a noun or a verb, though Dotter first used the term in cardiology in one of his published articles in Radiology in April 1983, which was titled “Transluminal Expandable Nitinol Stent Grafting: Preliminary Report.” the word stent is that it derives from the name of a dentist. Charles Thomas Stent (1807–1885) was an English dentist notable for his advances in the field of denture-making.[22] It could also be used as a verb in the context of stretching out sails, curtains, or fishing nets. Sigwart wrote in a letter to the editor of the American Journal of Cardiology that, “When submitting the first article on human stenting in 1986, the New England Journal of Medicine persuaded me to drop the verb 'stenting' and use instead the noun 'stent'.”[22],[23]

Jacques Puel and Ulrich Sigwart were invited almost simultaneously by the company Medinvent to help with the Initial animal and clinical research pertaining to their new product, the Wallstent. The first coronary stent was implanted into a patient by Jacques Puel in Toulouse, France, on March 28, 1986. Sigwart and Puel were the first to report on the clinical use of stents to prevent sudden occlusion and restenosis after transluminal angioplasty in their landmark work published on March 19, 1987, in the New England Journal of Medicine. The article reported their experience from Lausanne, Switzerland, and Toulouse, France, of ten stent implantations in six patients for iliac or femoral arterial disease; 24 coronary artery stents implanted in 19 patients who presented with coronary artery restenosis (n = 17) or abrupt closure (n = 4) after transluminal angioplasty or deterioration of coronary bypass grafts (n = 3).[23],[24] The successful use of stents in coronary arteries is considered as the second revolution in interventional cardiology.

Julio Palmaz, an interventional vascular radiologist, is known for inventing the balloon-expandable stent, for which he received a patent filed in 1985. This patent has been included on the list of the ten most important inventions of all times. Julio Palmaz from Argentina, and Richard Schatz, a cardiologist from the Brooke Army Medical Center, worked together at the University of Texas Health and Science Center at San Antonio. They miniaturized the Palmaz balloon-expandable stent for coronary use. The first Palmaz-Schatz coronary stent was implanted in Sao Paolo, Brazil.[25]

The Gianturco-Roubin (GR) Flex-Stent and the GR II Coronary Stents (Cook Inc.,) were the first Food and Drug Administration (FDA) – approved coronary artery stents in February 2002.[26],[27] The Palmaz-Schatz stent did not get approved until 1994, after the BENESTENT and STRESS randomized trials, comparing stents with balloon angioplasty.[28],[29] Within 4 years of FDA approval, the balloon expandable stent was used in 80% of percutaneous coronary interventions, a virtually unparalleled success.

In 1992, the landmark article “Intracoronary Stenting for Acute and Threatened Closure Complicating Percutaneous Transluminal Coronary Angioplasty” by Gary S. Roubin, Adam D. Cannon, Subodh K. [Figure 6], changed the way acute coronary syndromes were treated and to date primary PTCA has saved millions of lives across the globe.[30]
Figure 6: Roubin et al. Landmark article on stenting.

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The article which changed the rules! Primary PTCA was here to stay………….

There is yet another milestone probably sounding not too adventurous for the likes of interventional minds but all the same put forth “evidence based treatment” was establishment of registries which is seminal in causing acceptance of approaches and techniques.

  The Evolution of Drug Eluting Stents (The Third Revolution in Interventional Cardiology) Top

Bare metal stents problem: Thrombosis

Stents use exponentially increased in 90 s decade; however, this was halted by unacceptably high risk (20%–30%) of stent thrombosis leading to catastrophic complications such as MI and sudden death. To reduce stent thrombosis, patient were put on prolonged anticoagulation which reduced stent thrombosis to some extent but was associated with frequent and sometimes life-threatening bleeds and required prolonged hospitalization.[28] To reduce these complications of systemic anticoagulation, a novel method of stents coated with heparin was developed to decrease the thrombogenicity of stents (BX-VelocityCarmeda-coated stent (Johnson and Johnson), Wiktor Hepamed-coated stent (Medtronic, Inc.,), and the Jostent Corline-coated stent (Jomed International AB). Initial animal experiments demonstrated a significant decrease in stent thrombosis with no extra bleeding complications associated with aggressive systemic anticoagulation regimens.[31]

Around the same period, a pharmacological regimen after stenting different from the conventional approach was introduced by Paul Barragan and others in Marseilles:[30] the use of intravenous heparin and oral antivitamin K was progressively replaced by subcutaneous low-molecular-weight heparin and long-term treatment with aspirin and ticlopidine instead of warfarin. Subsequently, registries demonstrated a favorable impact of this regimen on subacute thrombosis and bleeding which further resulted in increased usage of stents. Around the same period, Colombo et al. also reported the beneficial effect of IVUS-guided high-pressure stent implantation in decreasing stent thrombosis.[32]

The heparin-coated stents were probably the first drug eluting stents (DES) though the mechanism of drug action was far different than the current DES.

Bare metal stents problem: Restenosis

Another problem that limited long-term success of stenting was high rate of restenosis, which affected almost 40%–50% of the patients undergoing PTCA.[33] Multiple cellular and molecular mechanisms are involved in a cascade of events that lead to restenosis – arterial injury during PTCA induces multiple signaling pathways that activate vascular smooth muscle cell (VSMC) migration and proliferation. Immediately after injury, VSMCs leave their quiescent state and enter the cell cycle, associated with the induction of early-response genes in-stent restenosis (ISR)-VSMC activation, migration, and proliferation. Marx et al. reported that rapamycin, a macrolide antibiotic, inhibited both human and rat VSMC proliferationin vitro by blocking G1/S transition.[34]

Gallo et al. found rapamycin (sirolimus) administration could reduce neointimal thickening in a porcine experiments post-PTCA predominantly due to VSMC inhibition.[35] Hence, finally, after trials of multiple drugs including antiplatelet agents, anticoagulants, angiotensin-converting enzyme inhibitors, and cytotlxic agents, a drug was found truly reducing the incidence of restenosis after angioplasty. However, there still remained the question of mode of administration to achieve the delivery of drug in significant quantity and for longer time to prevent actual restenosis in humans. Few clinicians tried oral rapamycin in the beginning; however, it did not decrease the rate of stent restenosis as the local concentration achieved at stent site was not enough to achieve inhibition of VSMC and high doses of systemic drugs resulted in unacceptable complications.[36] Hence, catheter-based local drug delivery systems were then developed to achieve high concentrations of drug at the site of vascular injury. Although they showed modest benefit in animal studies, they proved largely unsuccessful in humans because of the rapid washout of the drug in coronary circulation and also because the process of restenosis is a prolonged and catheter-based delivery are impractical for a prolonged period of time.[37]

After the initial failures with the drug delivery systems, the concept of using stent itself as a carrier vehicle for the pharmacological agents (rapamycin) looked attractive. Efforts were directed at coating a stent with a sufficient amount of medication that can be delivered uniformly to the underlying tissue for a prolonged period by means of coating of stents. Coating material needed to be biologically inert, many biological (fibrin, cellulose, albumin etc.,), synthetic polymers and inorganic coating materials were experimented on. The most successful coating material found were synthetic polymers: Poly-n-butyl methacrylate and polyethylene–vinyl acetate and a poly (lactide-co-Σ-caprolactone) copolymer which were used in Cypher and Taxus stents, respectively. Cypher and Taxus thus represented the first successful combination of stent, polymer, and biological agent (sirolimus and paclitaxel).[38],[39]

Eduardo Sousa implanted the first sirolimus-eluting stent in 1999 in first-in-man (FIM) study involving 45 patients. This study showed almost virtual absence of neointimal proliferation and no ISR over 2 years period. After the FIM, CYPHER has been tested in numerous randomized controlled trials, including RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS, and ISAR-DESIRE and showed a significant reduction in ISR and target vessel revascularization compared with bare metal stents. In 2002, CYPHER was approved by FDA and European medical agency.[40],[41]

Thus, DES represents final result of relentless efforts in pursuit of perfecting angioplasty, of scientific community, pharmaceutical and engineering industries, and clinicians. DES has gone significant change over time with newer biological agents (everolimus, zotorolumus, biolimus, novolimus, etc.,), polymer coating, and newer metallic platform (platinum chromium).

Next came along the vanishing act by introduction of “Absorb” bioresorbable vascular scaffold, the first drug (everolimus) eluting, fully bioresorbable scaffold, and has achieved a CE mark considered as the fourth revolution in interventional cardiology.[31],[33],[34] And over the years, there have been additions of, optical coherence tomography (OCT), micro-OCT, fusion imaging, fractional flow reserve, thrombectomy devices, and comebacks by rotational atherectomy, IVUS which have changed the way of management and fine tuning the interventional outcomes.[42],[43]

  Conclusion Top

Interventional cardiology has over the years been more such as a curious child with turbulent adolescence and mature middle age, thanks to the work of doyens in the field. The future is the age of new players and procedures, complex procedures which were hitherto sidelined, day care procedures, hybrid procedures with a heart team approach, integration of engineering and information technology, use of app-based patient consultation and dissemination of information, Uberisation of Health Care, three-dimensional application, robotics and health Insurance for all. The cath lab of tomorrow will serve to achieve collaboration of specialists in different fields which include interventional radiology, electrophysiology, peripheral interventions, vascular surgery, interventional neurology, structural heart procedures, and interventional oncology. There will be increase in the volume of procedures such as transcatheter aortic valve implantation, MitraClips, left atrial appendage closure devices, heart failure devices (Cardiomems, Circulite micro ventricular assist device, intra-arterial shunt device) vascular interventions, and veritably fine tuning the techniques with newer tools, software, and data base. In the age of being a global citizen, there is free flow of information and know-how's through the masters to the younger keener lot.

We would like to conclude with: “Let the hands which intervene be rested on shoulders with responsibility and respect for it with feet firmly on the ground aided by judiciousness and a balance of mind which would dictate the do's and don'ts and not see the person on cath lab table as an experimental tool; let our actions be guided by compassion and patient safety.”

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]


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