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64B JACC Vol. 31, No. 4 Suppl B March 15, 1998:64B–88B

The Development of Interventional Cardiology

SPENCER B. KING III, MD, FACC Atlanta, Georgia

Twenty years have passed since the beginning of clinical secretly and quickly. But I needed an assistant, the surgical interventional cardiology on the occasion of the first angio- nurse. I had to win her over or I would have no access to the plasty procedure performed by Andreas Gruentzig. This disci- necessary sterile instruments....Thefollowing afternoon the pline, which started as an added technique for physicians who good lady was sitting in her cubicle when I breezed in whistling performed cardiac catheterization, has evolved into a field cheerfully. ‘Nurse Gerta, I want you to give me a set of recently recognized by the American Board of Internal Med- instruments for a venesection under local anesthesia and a icine (ABIM) as deserving a board classification of its own urethral catheter.’ within cardiology. The certificate of added qualification, re- “She started up suspiciously. ‘But no one in the wards is cently approved by the ABIM and the American Board of scheduled for a venesection. You’re not planning to do that Medical Specialists, provides the framework for the interven- experiment of yours against boss’s orders, are you?’ ‘Nurse tional cardiology examination and the establishment of formal Gerta, you need to know nothing about what I am going to do fellowship programs of the Accrediting Council on Graduate but supposing I were to do the experiment—it would be safe.’ Medical Education (ACGME). It has been a fascinating 20 “She eyed me closely. ‘Are you absolutely sure there is no years filled with new discoveries, expanded technology and danger?’ clinical trials testing the technique against other therapies, and “ ‘Absolutely.’ it has stimulated a dramatically increased interest in vascular “ ‘Allright then, do it to me. I put myself in your hands.’ biology. I review many of the events that have shaped inter- “ ‘Well, why not? You’ll be the first person in history to ventional cardiology and speculate on some of the directions in undergo such an experiment.’ ” Forssmann states that he had which we may be headed in the future. no intention of going through with the experiment on nurse Gerta, but he did proceed to have her lie down on the Background for Angioplasty operating table and strapped her arms and legs to the table. He then proceeded to anesthetize his own arm while distracting Andreas Gruentzig is clearly the father of interventional her by applying iodine to her elbow. He describes how, with cardiology; however, he stood on the shoulders of those who one hand, he somehow made an incision over his own antecu- had gone before to make this work possible. J. Willis Hurst, in compiling the history of cardiac catheterization (1), recounted bital vein, opened the vein and inserted a urethral catheter some of the benchmarks that tell the story of the development about a foot into the vein. Releasing nurse Gerta, he said, of cardiac catheterization. In doing so, he selected the individ- “There we are. It is ready now. Call the x-ray nurse.” uals who were involved in these events to tell their own story. Forssmann then describes how the nurse was yelling at him Werner Forssmann is credited with performing the first because he had deceived her, but she did assist him down the cardiac catheterization in 1929 (2). He was not looking for a stairs to the X-ray room, placed him behind the fluoroscopy way to diagnose heart disease but rather for a way to inject screen and performed the X-ray recording. This adventure drugs more directly into the right atrium. To do so, he had to gained Forssmann derision and rebuke, but eventually, with overcome the prohibition of his chief, and he developed an the subsequent contribution of others, he was awarded the ingenous way to perform his experiment, as recounted in his Nobel prize. It is amazing what can be gained by being first in autobiography (3). “I decided to override Schneider’s prohibi- line. tion and go ahead with the experiment on my own heart There was little development in cardiac catheterization in the ensuing years. Klein, who was from Prague, used catheters to obtain blood samples to measure cardiac output (4). Later From the Andreas Gruentzig Cardiovascular Center, Emory University Hospital, Atlanta, Georgia. Andre Cournand and colleagues at Bellevue Hospital in New Manuscript received November 5, 1997; revised manuscript received Novem- York City extended the physiologic measurements (5,6). Much ber 24, 1997; accepted December 3, 1997. of this work was an outgrowth of the ravages of World War II Address for correspondence: Dr. Spencer B. King III, Emory University Hospital, Suite F606, 1364 Clifton Road NE, Atlanta, Georgia 30322. E-mail: and the necessity of finding ways to study the circulation in [email protected]. patients who were in shock as a result of blood loss.

©1998 by the American College of Cardiology 0735-1097/98/$19.00 Published by Elsevier Science Inc. PII S0735-1097(97)00558-5 JACC Vol. 31, No. 4 Suppl B KING 65B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY

The use of cardiac catheterization for diagnostic purposes Hurst identified Henry Zimmerman from Cleveland as the had to wait for the end of World War II. One of the earliest first to perform left heart catheterization (10). Zimmerman descriptions of cardiac catheterization for diagnostic purposes recounts his first experience with left heart catheterization (1): was reported in 1945 by Emmett Brannon, Heinz Weens and James Warren at Emory University (7). Warren recounted We had a fair idea of what was occurring on the right side of the how they built on the experience of Cournand and Richards at heart but could only guess what might be occurring on the left Bellevue (1): side of the heart. Dr. Claude Beck and I were discussing some cardiac problems dealing with the left side lesions and I An agency, the Office of Scientific Research and Development mentioned the possibility of catheterizing the left side of the (OSRD), was set up in Washington as a funding mechanism for heart. With one of his residents assisting, we did a number of supporting this research. It was under OSRD contract that the dogs, placing the catheter retrograde through an artery in the studies at Bellevue were undertaken. Lower Manhattan pro- leg into the left ventricle. Then after several in-depth confer- vided many casualties that simulated those on the battlefield. ences, my chief gave the go-ahead to attempt to place the The program was based in the Emergency Room at Bellevue catheter into the left ventricle of man. Hospital. Although highly commendable, this program was not large enough and efforts were made to establish another focus Zimmerman recounts how the catheter was inserted into the of studies on shock. As a result of this, Dr. Alfred Blaylock, radial artery after being lubricated with olive oil and was Professor of Surgery at Johns Hopkins, and a group of distin- passed retrograde into the left ventricle. The patient had guished physicians visited Dr. Eugene A. Stead, Jr., Professor severe aortic insufficiency, and they discovered that the dia- and Chairman of the Department of Medicine at Emory stolic pressure in the left ventricle was not elevated, and there University with offices in Grady Hospital. Their mission was was no systolic gradient on pullback into the aorta. simple. They wished to establish a shock unit at Grady because It is interesting that the development of coronary arteriog- its emergency room also had a considerable amount of trauma. raphy also occurred in Cleveland (11). Others had attempted I was particularly enthusiastic about the problem and volun- techniques for studying the coronary arteries (12–15). Some teered to go to New York to see the Bellevue operation for nondirect methods included visualization of the coronary myself. circulation by occlusion aortography by Charles Dotter (16), Warren, Stead and the group continued to make important the use of acetylcholine (17), phasic dye injections by Richards contributions regarding cardiac output under various physio- (18) and the use of aortic streaming techniques to alter the logic conditions (8), to understand the mechanisms of conges- intrabronchial pressure, inducing hypotension and using vari- tive heart failure (9). Warren recounts (1), ous catheters to opacify the coronary sinuses (19–21). All these attempts were inadequate, and it remained for Mason Sones to In some way the most exciting thing was the conceptualization perform the first direct coronary injections in 1958 and to that if an atrial septal defect was present, left to right shunting report the results at the American College of Cardiology of blood through the defect could be detected by appropriate meeting in Philadelphia the following year (22). sampling of blood. The presence of highly oxygenated blood, Sones recounts the first coronary arteriogram was inadver- which had been through the pulmonary circulation and the right tently performed in a patient undergoing left heart catheter- atrium, gave evidence of shunting even if the catheter did not go ization (1): through the atrial septal defect. I asked my associate to withdraw the catheter tip across the A 44-year old man with dyspnea on exertion for 9 years, an aortic valve into the ascending aorta so that we could complete enlarged heart and an accentuated pulmonary closure sound the procedure by performing an aortogram with the catheter tip was suspected of having an atrial septal defect, but the in the ascending aorta. My associate complied and we relied on diagnosis was not certain. Warren recalls the catheterization the pressure change from the left ventricle to the ascending (1). aorta without sliding the table top back under the 5 inch amplifier to confirm the exact location of the tip. I didn’t think The most exciting moment was when it could be seen after the this was necessary because I was quite certain that the catheter catheter had been advanced into the right atrium in a usual way, tip lay in the ascending aorta just above the aortic valve. My but then passed into the left atrium and then headward into associate, Dr. Royston Lewis, made an injection of 40 cc of 90% what we presume was pulmonary vein. Blood sample studies for Hypaque through the catheter. About one second before the oxygen content showed the classic and expected configuration. injection was initiated, I had the switch to initiate a cine run. The difference in color was apparent to the naked eye. There When the injection began, I was horrified to see the right had been some discussion of what the factors were that caused coronary artery become heavily opacified and realized the flow from the left atrium into the right. It had been suggested catheter tip was actually inside the orifice of the dominant right that pressure gradients related to posture might influence coronary artery. I shouted, “Pull it out.” Our combined reaction shunting. To test that theory, the patient was tilted in a head times to accomplish withdrawal of the catheter consumed from down position and the arterial blood oxygen saturation moni- 3–4 seconds which meant that approximately 30 cc of 90% tored. If shunting were to be reversed with flow from the right Hypaque had been delivered into the right coronary artery. I to the left, then oxygen saturation from the femoral artery was of course horrified because I was certain the patient would would fall. This did not take place. develop ventricular fibrillation. At that time we did not have 66B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B

direct current defibrillators and knew nothing about the appli- immigrating from East Germany, Gruentzig entered medical cation of closed chest cardiac massage. I climbed out of the hole school in Heidelberg and graduated in 1964. After a rotating and ran around the table looking for a scalpel to open his chest internship and a research fellowship in epidemiology, he began in order to defibrillate him by direct application of the paddles studying peripheral vascular disease at the Ratchow Clinic in of an alternating current defibrillator. I looked at the oscillo- Darmstadt, Germany. It was at this time that he first met scope tracing of his electrocardiogram and it was evident that Zeitler, who was speaking about peripheral recanalization by he was in asystole rather than in ventricular fibrillation. I knew that an explosive cough could produce a very effective pressure Dotter’s method. After his move to Zurich as a fellow under pulse in the aorta and hoped that this might push the contrast Alfred Bollinger in the angiology department, Gruentzig went media through his myocardial capillary bed. Fortunately, he was to visit Zeitler to observe the Dotter method. Gruentzig said, still conscious and responded to my demand that he cough “I not only observed the procedure itself during this time but repeatedly. After 3–4 explosive coughs, his heart began to beat also saw the patients before and after treatment and when they again with initially a sinus bradycardia which accelerated into a left the hospital I was very impressed with the improvement in sinus tachycardia within 15 to 20 seconds. He then made a peripheral ankle pressure as measured by ultrasound and by perfectly uneventful recovery with no neurological deficit or the fact that the patient was able to walk without any claudi- other sequelae. cation after successful catheter treatment” (32). Gruentzig invited Zeitler to Zurich to perform the first procedure at that Many would have been relieved to escape this apparent institution. Unfortunately, the plaque in the patient’s superfi- complication, but Sones saw immediately the potential for cial femoral artery embolized, lodging distally in the arteries of coronary arteriography and pursued this technique, thus open- the lower leg and obstructing blood flow. Gruentzig mused, ing the future for direct coronary bypass surgery and eventually “The radiologists who were skeptical from the very beginning, interventional cardiology. now had proof that the method was of no use whatsoever in The development of coronary bypass surgery is well de- human beings” (32). However, Gruentzig persisted with the scribed by its most prominent pioneer, Rene Favaloro, in this method, and with the encouragement of Wilhelm Rutishauser, supplement to the Journal (23). Favaloro gives credit to Sones, he entered cardiology training in the cardiac catheterization not only for developing coronary arteriography but also for laboratory. Gruentzig was convinced that the technique could training Favaloro himself in the technique and providing the not be applied in the coronary arteries without dramatic background that he needed for subsequently developing direct improvements; he said, “Everyone involved in the method at saphenous vein bypass. Favaloro also gives credit to Garrett for that time, including Charles Dotter, realized that any applica- performing the first coronary bypass procedure as a bailout tion of the dilatation procedure to other areas of the body during a planned endarterectomy in 1964 (24). He also credits would require technical changes” (32). W. Dudley Johnson, who was the first to demonstrate that In Berlin, Porstmann had developed a latex balloon with a grafting to the distal coronary segments could be performed, slotted angiographic catheter for attempting further expansion increasing the chance for multiple coronary bypass procedures of the peripheral arteries. Zeitler showed this to Gruentzig, but (25), and George Green, who pioneered the direct internal the system proved to be unworkable (30). Gruentzig set about mammary coronary anastamosis (26). to perfect a catheter that would provide a nondistensible So now, approximately 70 years from the beginning of balloon. Working in the evenings with his assistant, Maria cardiac catheterization, 50 years from the use of catheteriza- Schlumpf, and her husband, Walter, he tested many versions of tion for diagnostic purposes and 30 years from the advent of balloons, attaching them with thread and epoxic glue to coronary bypass surgery, we are 20 years into the field of diagnostic catheters. The first attempt at nondistensibility interventional cardiology. involved the use of a form of silk mesh that would entrap the Gruentzig’s ability to develop interventional cardiology was expanding balloon. With an interest in finding a very thin an outgrowth of these surgical developments enabled by material for the balloon, Gruentzig chose polyvinyl chloride coronary arteriography and the parallel development of trans- (PVC) at the suggestion of Hopf, a professor emeritus of luminal dilation of peripheral arteries by Dotter (27,28). chemistry in Zurich. Through the use of heat molding with Dotter’s genius was not recognized in the United States but compressed air, Gruentzig formed aneurysmal segments within was adopted in Europe by Werner Porstmann in Berlin and the PVC tubing. It was at this moment that he discovered that especially by Eberhardt Zeitler at Aggertal Klinik in Engel- the strength of the material was so great that the silk mesh was skirchen and later in Nuremberg (29–31). Zeitler, who had no longer necessary as an external constraining element. performed a large number of Dotter procedures was the man The first balloons built were mounted on a diagnostic who would teach Gruentzig the technique. catheter. A hole was punctured in the catheter so that the balloon could be inflated from the main lumen. To prevent the escape of fluid from the end of the catheter, an occlusion Development of Balloon Angioplasty stylette was passed end to end to block the catheter during I have recounted in a previous publication (32) the story of balloon inflation. Gruentzig could not persuade any company Andreas Gruentzig’s background, education and early investi- to build a double-lumen catheter, and the occlusion device gational work and only emphasize here the highlights. After catheter was large and bulky. He therefore devised a method JACC Vol. 31, No. 4 Suppl B KING 67B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY for replacing the PVC tubing with a distensible segment on the The catheter wedged the stenosis so that there was no ante- outside of an angiographic catheter. This created a coaxial grade flow and the distal coronary pressure was very low. To the design with the space between the diagnostic catheter and the surprise of all of us, no ST elevation, ventricular fibrillation or PVC tubing serving as a channel for inflating the balloon. The even extrasystole occurred and the patient had no chest pain. At angiographic catheter with one through-lumen no longer this moment I decided not to start the coronary perfusion with the roller pump. After the first balloon deflation, the distal needed to be occluded. coronary pressure rose nicely. Encouraged by the positive Maria Schlumpf recounted the long process required to response, I inflated the balloon a second time to relieve the perfect the double-lumen catheter, which was finally used for residual gradient. Everyone was surprised about the ease of the an iliac occlusion on January 23, 1975: “Continued work with procedure and I started to realize that my dreams had come the catheters finally resulted in a system that could be minia- true. turized to the size of a coronary artery.” The first experiments with that catheter were conducted with the help of the surgeon This patient remained free of angina, and when he under- Marco Turina. A silk ligature was tied around the coronary went recatheterization at Emory on September 16, 1987, the artery of a dog, producing a constricting stenosis. On Septem- anterior descending coronary artery was widely patent. Ten ber 24, 1975, these animal experiments were begun and were years later, he remains asymptomatic and in September 1997, subsequently reported at the American Heart Association he performed a maximal bicycle ergometric test with normal meeting in 1976. The responses to Gruentzig’s presentation at results. The second successful procedure was performed with the meeting were not overwhelming (33). However, several Kaltenbach in Frankfurt. Gruentzig continued to develop the important contributors saw the presentation, including Martin technique by selecting relatively ideal cases as well as experi- Kaltenbach, Richard Myler and John Abele. The exhibit was menting with more challenging situations. By the time he left pointed out to me by Paul Lichtlen, who had been in Zurich in Zurich to join our group at Emory University, he had per- the early 1970s and who was then chief of cardiology in formed 169 procedures. Long-term follow-up of these patients Hanover, Germany. My reaction was, “This will never work.” showed excellent results and a 90% survival rate at 10 years Nonetheless, this meeting with Gruentzig was crucial to my (34,35). eventual conversion to his point of view. At the Scientific Sessions of the American Heart Associa- The application of this technique to human coronary arter- tion (AHA) in 1977, Gruentzig was to present a paper entitled ies would be challenging. To develop the procedure in a safe “Coronary Transluminal Angioplasty.” It was assumed that he manner, Gruentzig insisted it be performed during bypass would be presenting the update of the canine experiments; surgery so that patients would not be jeopardized. The sur- however, during the presentation, he reported on the first four geons in Zurich were not enthusiastic about producing com- patients who had undergone angioplasty. After describing the petitive flow by dilating a lesion that was about to be bypassed, fourth patient, whose left mainstem dilation demonstrated but Myler and Gruentzig convinced Elias Hanna, a surgeon at excellent angiographic success, the audience interrupted the St. Mary’s Hospital in San Francisco, to assist them with this presentation with applause. Gruentzig said, “I was so surprised endeavor. Hanna indicated that his grafts would “always be that I almost could not proceed with my 10 minute presenta- better than what was accomplished with dilatation” (32). tion. After the lecture, Sones came to me and asked for proof On returning to Zurich, Gruentzig finally had an opportu- of my results. I invited him to share with me the cineangiogram nity to perform his procedure in a patient. This patient had which I had in my suitcase. We went to the exhibition hall and unstable angina, severe multivessel disease with left mainstem reviewed the film on this patient together at the booth of one stenosis and severe peripheral vascular disease. The femoral of the exhibitors” (32). arteries could not be intubated, and only the left brachial artery would allow passage of the catheter to the aorta. Because of the difficult entry site and cumbersome equipment, Dissemination of the Technique Gruentzig was unable to intubate the coronary artery with the Gruentzig continued to perfect the technique, and patients dilation catheter, and the procedure was abandoned. This came from distant parts of the world to have the procedure experience radically changed Gruentzig’s mind regarding the performed. The first American patient recounted his experi- selection of patients for untested techniques. The first success- ence to me. He was having severe angina and saw Lamberto ful angioplasty was performed on September 16, 1977. The Bentivoglio in Philadelphia, who told him that there was a new patient was 38 years old (the same age as Gruentzig) and had therapy available. Bentivoglio described percutaneous translu- a discrete lesion in the proximal anterior descending coronary minal coronary angioplasty and offered to perform the proce- artery and disabling angina. Bernhard Meier, who as a resident dure. The patient was enthusiastic but decided to go to Zurich. in Zurich was caring for the patient at the time, recounts that I have subsequently studied the patient; 10 years later, his left even though Gruentzig told the patient that he was the first to anterior descending coronary artery (LAD) remains visibly undergo the procedure, the patient was enthusiastic to have an patent with no recurrence of stenosis. alternative to bypass surgery. With all the senior staff of the There was understandable enthusiasm, and many wanted to hospital in attendance, Gruentzig performed the procedure visit Gruentzig in Zurich to see balloon angioplasty firsthand. and recalled (1), Aleardo Maresta remembers that during his 2-month visit in 68B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B

Zurich at that time, Gruentzig was becoming increasingly (43,44) and was applied clinically (45,46). Subsequently, au- uncomfortable with visiting physicians in the catheterization toperfusion balloon catheters with holes proximal and distal to laboratory. To share his experience in a more organized way, the balloon allowed flow during balloon inflation (47–50). Gruentzig instituted closed-circuit televised demonstration These balloons were used for improving the initial results of courses, the first of which was held in 1978 with 28 physicians angioplasty but more often in coping with complications that in attendance. In March 1978, Myler in San Francisco and arose during the angioplasty procedure. Maintenance of per- Simon Stertzer in New York introduced coronary angioplasty fusion was a technique used to ensure less ischemia while in the United States. The technique spread rapidly; from a few moving the patient to the operating room for surgical repair of thousand procedures performed before 1980, more than the abrupt closure resulting from angioplasty (51). Surgery was 30,000 procedures were performed in 1983. Most of the often indicated after failed angioplasty, and techniques for interest during these early days of angioplasty was in finding improving urgent surgical intervention were developed. Close improved ways to use the balloon catheter and ancillary collaboration with the surgeon took precedence over the devices. inevitable feeling of competition and resulted in a surgical Gruentzig’s move to Atlanta started with a conversation mortality rate for failed angioplasty of only 1% at our center that we had in Zurich in which he expressed his dissatisfaction (52–54). with the constraints placed on him in developing the technique One of the most important developments in guide catheter in Zurich. I suggested that he visit us at Emory, and with the technology was the development of the soft-tipped catheters by help of Willis Hurst and others, we finally recruited him. John Van Tassel and colleagues (55). This technology has since been Douglas and I had been struggling with angioplasty and were adopted by all manufacturers to reduce catheter tip trauma. delighted when Gruentzig joined us in October 1980. In one of the meetings in Zurich, John Simpson approached me (and probably many others) and asked my opinion regard- ing his idea of using a guidewire within the balloon catheter as Early Angioplasty Equipment a rail on which the catheter would travel. The disadvantage In the early days of angioplasty, the guide catheters were would be the lack of ability to measure pressure adequately made of Teflon and were extremely stiff. The balloon catheters with the guidewire in place, and the advantage would be an were of a double-lumen design with a closed end and a short improved ability to direct the catheter through the lesions. guidewire attached directly to the end of the balloon. There Because no steerable guidewire was available, this seemed a was no practical way to steer these DG catheters. The catheters minor difference from the then available fixed-wire systems. were high profile, and to recross the lesions after dilating them He told me of his options to start a company that would make was considered extremely dangerous. The procedure was such a device or to sell the idea to some existing companies. I guided by angiographic assessment and by measurement of the advised him to sell his idea immediately if someone was willing change in pressure gradient across the lesion. Pressures were to pay for it. Fortunately, he did not follow my advice, and the measured from the tip of the balloon catheter and from the tip over the wire balloons were born. The problem of steerability of the guide catheter. Even though the balloon catheter was remained severe because the wires were cumbersome and high profile, a significant reduction in gradient could be offered little advantage over the previous system. documented. In addition, the value of collateral channels could In 1982, at the urging of Gruentzig and others, companies be determined with the wedged balloon catheter pressure began to make steerable guidewires. We used them first in measurement, which Gruentzig studied extensively (36). 1982 in one of our courses and found them to be a remarkable Because of the lack of steerability of the balloon catheter, it improvement over previous wires. As Patrick Serruys reflected was necessary to achieve selective intubation or at least on the improvements in coronary angioplasty during the past selective direction of the guide catheter toward the artery to be 20 years, he felt the steerable guidewire stands out as the most intubated. There was, therefore, great interest in improving the dramatic improvement. In an examination of the success and guide catheters. Techniques were developed for directing the complication rates at Emory University, I found that after guide catheter selectively into the anterior descending or steerable guidewires became available in 1982 through 1984, circumflex artery to achieve an adequate platform for passage the angiographic success rate increased from 83% to 93%, the of a large-profile balloon catheter (37), to achieve an adequate clinical success rate increased from 79% to 91% and the backup platform to cross tight lesions with these high profile emergency bypass surgery rate decreased from 7.2% to 2.8%. catheters (38), for exchanging guide catheters while keeping Although many improvements have been made in the succeed- the guidewire in the artery (39) and for shaping specially bent ing years, there has been no greater incremental change in guide catheters to allow access to unusual anatomy (40–42). success and complication rates than that occurring after the Balloon catheters were occlusive and in many cases pro- development of steerable guidewires. duced ischemia. Kaltenbach and colleagues demonstrated ex- During the early days of the guidewire industry, Gruentzig perimentally that inflations needed to be prolonged to 45 s to accompanied the officials of USCI to the Dupont Company. completely express fluid from them. Interest grew therefore in Dupont manufactured polyethylene terathalate, which is a very sustaining inflations while maintaining distal flow. Perfusion, strong noncompliant material. The company did not feel that using the patient’s own blood, was achieved experimentally making tiny balloon catheters would be a profitable venture JACC Vol. 31, No. 4 Suppl B KING 69B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY because the amount of material needed for one 2-liter Coca- elsewhere, was necessary in 23% of these patients over the Cola bottle would probably supply USCI for a year! Neverthe- 10-year period. Others also have reported encouraging long- less, Gruentzig’s persuasive manner prevailed, and the era of term results after angioplasty (71). We evaluated the long-term improved balloon materials began. Since then, many additional follow-up data of the first 471 patients treated at Emory improvements have been made to ensure low profile and high University in 1981. These patients had predominantly single- pressure capability in balloon catheters. vessel disease (88%), and the 10-year survival rate was 91% As the equipment improved, operators looked for uses (72). other than lesions in the major coronary arteries. Bifurcation lesions are very common, and there was great interest in dealing with these. The so-called kissing balloon techniques Development of Multicenter Registries and various modifications were popularized in the early and Among those who listened to Gruentzig’s presentation at mid-1980s (56–64). Others tried to develop better methods for the 1977 AHA annual meeting was Michael Mock, Chief of the dilating lesions on curves (65,66). National Heart, Lung, and Blood Institute (NHLBI) Cardiac Several methods of exchanging wires, from short over the Diseases Branch. Suzanne Mullin Cowley, who worked in data wire systems with extension segments to the long-wire tech- management in the Cardiac Diseases Branch, remembers that nique of Kaltenbach, were developed (67). The development Mock held an impromptu brown bag lunch with Gruentzig to of the monorail systems represents an interesting story in discuss the results in the first patients and then returned to interventional cardiology. Moving the guidewire from its usual Washington to discuss options with Robert Levy, Director of coaxial position in the catheter was a major departure from NHLBI. In January 1979, a small working group that included conventional thinking (68–70). Richard Myler, Simon Stertzer, John Simpson and Peter Block There was a brief departure from guidewire catheters back met with Mock to discuss ways to evaluate the technique. to the fixed-wire systems with the development of very low Early investigators of angioplasty believed that the results profile devices. The Hartzler catheter from ACS, the Probe should be carefully documented, and with the help of individ- catheter from USCI and the ACE catheter from Scimed had uals at the NHLBI, notably Mock, a registry was formed no moveable guidewires but were steerable catheters that were (73–75). The data center at the University of Pittsburgh, essentially a balloon on the wire itself. These devices filled a headed by Katherine Detre, was selected as the core data niche until balloon materials and balloon catheter technology center for this first NHLBI PTCA registry. This registry and improved and made them usually unnecessary. However, these the subsequent registry of data collected in 1985 to 1986 (73) “on the wire” balloons still have the ability to cross lesions that would become important benchmarks for the performance of other catheters cannot cross. balloon angioplasty and for comparison with future interven- tional techniques. Many others during this time also docu- mented improving success rates, within the first 1 to 2 years Assessment of Angioplasty Outcomes after the angioplasty began, success rates in the high 80s were Evaluation of the early and long-term outcomes of angio- being achieved. plasty was a major effort in the early and mid-1980s. A number of series were examined in registry format. We had the opportunity to carefully follow up all patients undergoing Improving Outcomes angioplasty by Gruentzig in Zurich between 1977 and 1980. Evaluation of angioplasty was concentrated primarily on These patients were very symptomatic, relatively young and understanding the correlates of successful procedures, compli- had well documented ischemia on stress testing and either cations and restenosis rates. Most evaluations were performed one-vessel disease or a large, high grade culprit lesion in a in patients with predominantly single-vessel disease or single single vessel. Gruentzig’s primary purpose in selecting such culprit lesion interventions (76). The rate for major acute patients was, first, to have target lesions that could be treated complications at Emory among the first 3,500 patients (77) was with the equipment available at that time and, second, to 4.1% and included 2.7% for emergency operation, for myocar- document correction of the ischemic insult by decreased dial infarction 2.6% and 0.1% for death. The five preproce- symptoms and improved functional testing. With a grant from dural predictors of major complications were multivessel dis- USCI, we were able to follow up these patients completely for ease, lesion eccentricity, presence of calcium, female gender 10 years. Maria Schlumpf, Gruentzig’s long-term assistant, and lesion length. However, the greatest predictor was a maintained contact with all 169 patients throughout the postprocedural dissection, which carried a sixfold risk of a follow-up period. The survival rate of patients who underwent major complication. successful angioplasty was 90% at 10 years. Those with true The consequence of abrupt closures was also studied. Two single-vessel disease had a 95% survival rate. Importantly, centers evaluated 8,207 consecutive procedures that resulted in most of these relatively young patients were smokers, and after 294 acute coronary occlusions (4.4%) (78). The three indepen- angioplasty, most were convinced not to smoke—a factor that dent variables identified as predictors of death were collateral was perhaps also important in their long-term clinical benefit channels originating from the dilated vessel (indicating occlu- (34,35). Bypass surgery, for these lesions or progressive lesions sion of other vessels), multivessel disease and female gender. 70B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B

An analysis of 32 deaths at Emory, San Francisco Heart and fatty acids) had mixed results (140–145); however, this ap- the University of Michigan Hospitals revealed that the most proach has not been adopted. Corticosteroids applied in common mechanism of death—left ventricular failure due to several trials, notably the Multi-Hospital Eastern Atlantic vessel occlusion—was correlated with female gender, “jeopar- Restenosis Trial (M-HEART) (146) and a single-center study dy score” and angioplasty of the proximal right coronary artery (147), failed to show benefit. Antimitotic agents were proposed (79). (148,149), as was colchicine (150). Vasoactive compounds, The major complication at this time was abrupt closure of such as calcium channel blocking agents, have been used the artery, necessitating urgent bypass surgery. This complica- without significant effect (80). Angiotensin converting enzyme tion was variously thought to represent coronary spasm, (lead- (ACE) inhibitors were found to suppress the vascular response ing to the use of calcium antagonists during and after angio- to injury in a rat carotid model (151), and that finding led to plasty [80]), dissection (77,81,82) or thrombosis (83). two large multicenter trials of ACE inhibition, both of which were negative (152,153). Angiopeptin, a somatostatin analog, also showed potential for antiproliferative activity (154). An Restenosis initial clinical trial was promising; however, larger trials proved The restenosis process, initially predicted to occur in ϳ30% negative. With the advent of powerful HMG coenzyme A of patients, became a major problem with angioplasty. Numer- reductase inhibitors, a dramatic lowering of serum cholesterol ous reports of the incidence of restenosis began to appear levels could be achieved. This method was tested in a con- (84–91). The pathologic mechanisms of restenosis have been trolled, randomized trial of lovastatin that resulted in a dra- studied by a number of investigators (92–98). The restenotic matic decrease in cholesterol levels but no change in the lesion was found to be composed of cells very similar to smooth incidence of restenosis (155). Subsequently, two other trials of muscle cells with a great deal of extracellular matrix (95,98– HMG coenzyme A reductase inhibitors were conducted that 106). Various correlates of restenosis were identified in the showed the same negative result (156,157). guidelines for angioplasty published in 1988 (76). Some of the Although no compound has been documented in large conditions associated with an increased rate of restenosis were randomized trials to reliably reduce the restenosis rate, several coronary spasm (107–110), lesion location (111,112), lesion have recently provided some hope. Trapidil, helpful in the morphology (113), serum lipid concentrations (114,115), the rabbit model (158), is purported to inhibit the effects of presence of unstable angina pectoris (116–119), lesions with platelet-derived growth factor and was associated with a sig- previous angioplasty (120–123) and multivessel disease nificant reduction in restenosis in a small trial in Japan and in (124,125). Vein graft lesions had the greatest restenosis rate, another, the Study of Trapidil Versus Aspirin in Coronary followed by the LAD, particularly the proximal LAD, with the Restenosis (STARC) II trial, in Italy (159). An expanded trial circumflex and right coronary arteries having lower restenosis of 1,200 patients is under way (Maresta A, personal commu- rates (126). Other correlates of restenosis were percent steno- nication, September 1997). Likewise, probucol, an antioxidant sis before (126) and after angioplasty (127,128), lesion length with low density lipoprotein–lowering effects, has shown en- and the translesional pressure gradient after balloon angio- couraging results. In our laboratory, probucol was investigated plasty (129). along with lipid-lowering agents in the porcine overstretch Reported restenosis rates in the 1980s varied considerably restenosis model (160). No effect was found with lipid-lowering from 12% to 53%. Much of this variation depended on the agents, but probucol did result in a significant reduction in number of cases restudied. The higher the restudy rate, the neointimal formation, suggesting that any benefit was due to its lower the restenosis rate, because symptomatic patients tend to antioxidant properties. One study from Japan (161) and an- present for repeat angiograms more frequently. In a landmark other from the Montreal Heart Institute (162) have shown a report, Nobuyoshi et al. (130) documented the time course to reduction in the restenosis rate only when probucol was given restenosis in patients undergoing serial angiography. Although for 1 month before intervention. Both studies are relatively there was infrequent restenosis at 1 month, most had occurred small, and further work in this area is needed. by 3 months, although some restenosis continued to occur at 6 Because of disappointing results with restenosis trials of months and beyond (130). systemic therapy, there has been great interest in delivering In an effort to control the restenosis process, our group and drugs locally. Various balloon delivery systems, starting with others attempted to alter the balloon angioplasty procedure to the porous balloon and many other versions, have been used in achieve an improved long-term result (131–134). However, an attempt to achieve a high local concentration of drugs restenosis rates seemed to be independent of operator tech- (163–166). To date, none of these methods has proven signif- nique and procedural alterations. icantly effective in animal models or patients, possibly because Early randomized trials addressed the problem of resteno- of their inefficient drug delivery. Perhaps techniques for sus- sis by comparing anticoagulation regimens (83,135–139). Al- taining drug concentration in the arterial wall will be achieved though antiplatelet agents were effective in preventing acute in the future. Endovascular radiation or brachytherapy is the complications (137,138), none of these studies showed that latest attempt at local delivery for restenosis prevention. antiplatelet or anticoagulant strategies influenced restenosis Animal studies have been dramatically positive, and recent rates. Other clinical trials of agents such as fish oil (omega-3 pilot studies in patients with primary lesions and those with JACC Vol. 31, No. 4 Suppl B KING 71B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY restenosis have shown very encouraging results (167,168). Late correlated hospital mortality with the number of vessels in- lumen loss was virtually eliminated at the 6-month angio- volved. The in-hospital death rate was 0.9% for patients with graphic follow-up. Further randomized trials are under way. two-vessel disease, 2.2% for those with three-vessel disease and 8% for the few patients with dilated left main coronary stenoses. The Move to Treatment of Clinical and angiographic follow-up data were obtained in numerous studies of patients with multivessel disease through- Multivessel Disease out the 1980s (177,183–188). Mean follow-up, which averaged Although angioplasty of a single lesion that was causing the ϳ2 years, showed that mortality rates were 1% to 8.5%. The ischemic syndrome was the major objective of the initial Zurich rate of repeat procedures also had a wide range, with 9% to series, 71 of those first patients had multivessel disease. The 35% for repeat angioplasty and 6% to 17% for bypass surgery. procedure was successful in 52 (73%) of the 71 patients, and a In the NHLBI PTCA Registry (189,190), 5-year survival rates single lesion was dilated in all but 2 patients. The 6-year were 93% for patients with single-vessel disease and 87% for survival for those patients was 92%; 17% required repeat patients with multivessel disease. Subsequent studies of bal- angioplasty and 14% repeat surgery. During long-term loon angioplasty performed during the 1980s showed compa- follow-up (Ͼ10 years), 54% remained asymptomatic (34,35). rable results (191–196). However, most investigators, continued to perform angio- Improvements in angina were documented by Myler et al. plasty in patients with single-vessel disease. It was Geoffrey (197), who reported that among 488 patients with multivessel Hartzler who pushed the envelope in the early 1980s to treat disease, baseline Canadian Cardiovascular Society (CCS) an- more patients with multivessel disease (169). In the early to gina status was class II in 46%, class III in 42% and class IV in mid-1980s, Hartzler, through his training courses, encouraged 12%. At follow-up, 97% of the patients were classified as class operators to explore opportunities for treating patients with I or II. Another study of patients with multivessel disease multivessel disease, and there was invariably a conflict between followed up for 2.5 years showed that functional class im- those operators who favored the more conservative and those proved in 82% of patients (177). the more aggressive approach. Importantly, neither Hartzler nor Gruentzig entered into controversy on a personal level. Throughout the 1980s, there were numerous observational Completeness of Revascularization studies in patients with multivessel disease (170–179). These Angioplasty in patients with multivessel disease often re- reports from 1983 to 1988 showed the number of lesions sults in incomplete revascularization. Previous surgical experi- attempted per patient to range from 1.9 to 2.7 and the ence led to the conclusion that complete revascularization in angiographic success rates per lesion from 80% to 92%. patients undergoing bypass surgery was superior to incomplete Complications included in-hospital death (0% to 1.9%), myo- revascularization (198–200); however, this has not been dem- cardial infarction (1.6% to 5.1%) and the need for emergency onstrated with angioplasty. Angioplasty, by its nature, is unable operation (1% to 6.4%). The initial registry of coronary to provide revascularization as complete as that by bypass angioplasty was reopened in 1985 and 1986 to collect data on surgery, primarily because of the presence of totally occluded a more contemporary series of patients now that the practice of vessels but also because of the reluctance to dilate less severe angioplasty had matured (180). stenoses that would ordinarily be bypassed. Vandormael and In the NHLBI PTCA Registry of 1,802 patients undergoing Deligonul (201) collected a series of reports examining the elective angioplasty, 568 (32%) had two-vessel disease, and 395 completeness of revascularization with balloon angioplasty (22%) had three-vessel disease. Fifty-three percent of patients during the 1980s and found that the incidence of complete with two-vessel disease and 59% of patients with three-vessel revascularization ranged from 21% to 47% (177,202–207). In disease underwent multilesion angioplasty. The success rates the experience of Vandormael et al (203), only one third of parallel those of the other single-center studies, with successful patients fulfilled the criterion of no residual stenosis Ͼ50%, dilation in 79% of the patients with two-vessel disease and 78% but when restenosis was redefined as freedom from stenosis of the patients with three-vessel disease. At least one lesion Ͼ70%, approximately half of their patients were considered to was successfully dilated in Ͼ90% of patients with multivessel have complete revascularization. There has been reluctance to disease. That registry has served as a benchmark for future dilate less severe lesions because of the chance of stimulating balloon angioplasty and device experience. The complications a restenotic process (208). Noninvasive testing is frequently of multivessel angioplasty were further explored by Myler et al. used with angioplasty to identify physiologically significant (181), who classified their patients into those with single lesions by areas of documented ischemia on exercise thallium discrete lesions in each of the vessels dilated and those with at imaging or stress echocardiography (209). least one complex lesion characterized by long stenoses, total A number of centers have documented improved event-free occlusions, bifurcation lesions, saphenous vein graft lesions or survival rates in patients with multivessel disease who could internal mammary artery stenoses. The only in-hospital deaths undergo more complete revascularization (210). A report from in this study of ϳ500 patients occurred in the group with the the NHLBI PTCA Registry (211) showed that 127 patients more complex lesions. The NHLBI PTCA Registry data (182) with complete revascularization fared better than 159 patients 72B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B with incomplete revascularization in terms of death, myocar- Randomized Trials of Angioplasty dial infarction and need for bypass surgery. However, the Randomized trials that compared bypass surgery with med- baseline features of the patients with incomplete revascular- ical therapy were conducted in the 1970s amid criticism that ization were different from those of patients who could have angioplasty was being performed in a large number of patients; complete revascularization. Logistic regression analysis of the however, no direct comparative trials were carried out. Obser- patients in the NHLBI PTCA Registry, adjusting for left vational studies continued (215–218), and in the late 1980s, Ͻ ventricular ejection fraction 50%, previous myocardial in- true randomized trials were begun. Gruentzig conceived of a farction, CCS class III or IV angina, age and geometry of the comparison of angioplasty versus bypass surgery in the early lesion, showed that the estimates of future death, myocardial 1980s but did not believe the technique was sufficiently mature infarction or angina were no longer significantly different for a direct comparison until about 1984. Application was between the two groups. Our group at Emory performed an made for a National Institutes of Health grant to support such observational study in patients with two-vessel disease; 417 a trial, but funding was not provided, and Gruentzig died patients undergoing coronary angioplasty and 503 bypass sur- without the opportunity to see the results of such comparisons. gery were followed up for 5 years. There were multiple Ultimately, EAST was resubmitted and approved for funding differences in baseline characteristics, including younger age, in 1987 and became the first U.S. trial to be launched. EAST less diabetes, less myocardial infarction, less severe angina and was soon followed by BARI, starting 1 year later. Other trials less LAD involvement in the angioplasty group. Completeness were initiated in Europe and South America; to date, nine of revascularization was greater in the bypass surgery group, as randomized trials directly comparing angioplasty and bypass indicated by 3.4 grafts/patient, than in the angioplasty group surgery have been carried out. Clinical outcome at 1 year was with 1.5 lesions dilated/patient. After adjustment for baseline assessed for eight of these trials in a meta-analysis (219). differences, there was no difference in survival between the There was no difference in hospital or 1-year mortality or bypass surgery and coronary angioplasty groups (212). No myocardial infarction between the angioplasty and bypass randomized interventional cardiology study to date has com- surgery groups. Three of the trials included patients with pared intentional incomplete revascularization with inten- one-vessel disease. In those patients, the 1-year mortality rate tional more complete revascularization. Therefore, all the was 0.3% for the bypass surgery group patients and 1.9% for observational studies are fraught with significant bias. the angioplasty group patients. In the trials involving patients The Emory Angioplasty Surgery Trial (EAST), which is with multivessel disease, the 1-year mortality rate for the discussed later, did give some insight into the difference bypass surgery group was 2.8% and 3.1% for the angioplasty between bypass surgery group patients with more complete group. The major differences between these groups was in the revascularization versus comparable angioplasty group pa- number of repeat procedures. Repeat angioplasty or bypass tients (213). Almost all segments that were obstructed were surgery was required in 33% of angioplasty group patients and bypassed in the surgery group and 71% were bypassed in the only 3% of bypass surgery group patients at the end of 1 year. angioplasty group. Protocol-mandated follow-up angiograms Some of the lessons learned from these trials are summarized were obtained at 1 and 3 years and showed sustained revascu- here. larization in 88% of the targeted segments in the bypass The EAST trial (213) consisted of 392 patients with mul- tivessel disease, of whom 40% had three-vessel disease and surgery group versus 59% in the angioplasty group. By virtue of 60% two-vessel disease. This trial had a protocol of 1- and repeat procedures performed, that difference in percent of 3-year follow-up visits, thallium scanning and coronary arte- revascularized segments narrowed by 3 years to 87% in the riography. The primary end point was a composite of death, Q bypass surgery group versus 70% in the angioplasty group. Ͼ wave myocardial infarction or a large ischemic defect found on When only severe ( 70% stenosis) lesions were considered, thallium scanning. Other end points were death, myocardial the difference in revascularization between the angioplasty and infarction, repeat bypass surgery and repeat angioplasty. Forty bypass surgery groups at 3 years became nonsignificant, which percent of the EAST and BARI patients had three-vessel may partially account for the fact that survival between the two disease, and the remainder had two-vessel disease. All were groups was not different at 3 years (214). eligible for both angioplasty and bypass surgery (220). The There can be little argument that complete revasculariza- results of EAST, which were published in 1994, showed no tion is preferred to incomplete revascularization when possi- difference between angioplasty and bypass surgery regarding ble. However, some of the motivation for complete revascu- the primary end point or death. The overall survival rate at 3 larization with bypass surgery is to avoid the necessity of going years was 93.5%; with 5-year follow-up, the overall survival back into the chest should mild lesions progress and for rate is ϳ90% with no significant difference emerging between bypassing totally occluded segments, some of which serve the angioplasty and bypass surgery groups. The principal nonviable myocardium. If these two categories of lesions can difference between the groups in the EAST trial, as was found be excluded, then angioplasty represents an opportunity in in all the other trials, was the need for repeat intervention. At many patients to provide initial physiologic revascularization the 3-year defined end point of the trial, repeat bypass surgery comparable to that of bypass surgery. had been performed in 1% of bypass surgery group patients JACC Vol. 31, No. 4 Suppl B KING 73B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY and 22% of the angioplasty group patients. Subsequent angio- wisdom regarding treatment selection. It is therefore impor- plasty had been performed in 13% of bypass surgery patients tant to maintain registries of eligible but not randomized and 41% of angioplasty group patients. CCS class II or more patients, as was done for the EAST trial. In that study, in severe angina was present in 20% of the angioplasty cohort and addition to the 392 randomized patients, 450 patients were 12% of the bypass surgery cohort at 3 years. Seven- to 10-year eligible but were not randomized either because the patient or follow-up data are now being tabulated to determine whether the referring physician refused. The recorded baseline features any difference in survival will emerge between the two treat- in these patients were remarkably similar to those in the ment groups. The more complete revascularization of bypass randomized patients (40% had three-vessel disease and 60% surgery may be protective over time, or the predicted late had two-vessel disease; mean age in both groups was 62 years, attrition of vein grafts may influence survival and events in the left ventricular ejection fraction was 60%, previous myocardial opposite direction. infarction had occurred in ϳ40%, diabetes was present in 22%, The BARI trial included 914 patients randomized to bypass hypertension was present in 52%, congestive heart failure was surgery and 915 to coronary angioplasty (221). This trial was present in 3%). Analysis of the angiographic lesions also did powered for a primary end point of overall mortality at 5 years. not show dramatic differences. The major variable between the The survival rate at 5 years was 89.3% for the bypass surgery patients in the randomized trial and those of the registry was cohort and 86.3% for the angioplasty cohort (p ϭ 0.19). The the use of the therapeutic methods. The treatment applied in initial in-hospital mortality rate was 1.3% for the bypass the registry patients was largely that selected by the attending surgery group and 1.9% for the angioplasty group. As in the physicians and sometimes that selected by the patients them- EAST trial, the incidence of repeat revascularization was much selves. This judgment resulted in most of the patients with higher in patients randomized to undergo angioplasty. At 5 three-vessel disease undergoing bypass surgery and most of the years, 8% of the bypass surgery cohort had undergone addi- patients with two-vessel disease undergoing angioplasty (226). tional revascularization procedures compared with 54% of the At the end of 3 years, the survival rate for the registry patients angioplasty cohort. The two U.S. trials, EAST and BARI, are was 96.4% compared with 93.4% for the randomized cohort highly comparable, with 40% and 41% of patients having (p ϭ 0.044). Although it is not possible to directly compare three-vessel disease and the mean age being ϳ62 years in both these patients because they are not identical, the excellent studies. survival in the very similar registry patients cannot be ignored. The Coronary Angioplasty Versus Bypass Revasculariza- It can be argued that the judgment provided by the attending tion Investigation (CABRI) (222) included 1,054 patients with physicians in making the treatment choice was influenced by multivessel disease. The 1-year mortality rate was 2.7% for the variables that were not directly measured in the trial. One trial, bypass surgery group and 3.9% for the coronary angioplasty Angina With Extremely Serious Operative Mortality Evalua- group. The Randomised Intervention Treatment of Angina tion (AWSOME), enrolling patients who are at high risk for (RITA) trial (223) was a study of 1,011 patients, with the bypass surgery, is being conducted in several Veterans Affairs primary end point of a combination of death or myocardial hospitals. The question being asked is whether these high risk infarction at 5 years. In the RITA trial, as opposed to the patients, including those facing a second operation, managed EAST, BARI or CABRI trials, half of the patients had with interventional techniques will have a superior outcome one-vessel disease. The 2.5-year mortality rate was 3.6% for compared with bypass surgery. the bypass surgery group and 3.1% for the angioplasty group. Randomized trials of angioplasty versus medical therapy Subsequent angioplasty was common (31% in the angioplasty have been limited. The Angioplasty Compared to Medicine group). Other randomized trials included the German Angio- (ACME) trial (227), conducted in the Veterans Affairs system, plasty Bypass Investigation (GABI) (224) and the Argentina compared 212 patients not in need of urgent revascularization Randomized Trial of Angioplasty Versus Surgery (ERACI) who underwent assignment to an angioplasty or a conservative (225). Each of these trials included patients with multivessel therapy group (227). Most of these patients had one-vessel disease; again, the 1-year survival rates showed no difference disease. No difference could be demonstrated in survival, but, between angioplasty and bypass surgery. the angioplasty group patients had a decrease in angina and an There are certain limitations to randomized trials of angio- increase in exercise tolerance. A recently completed study, the plasty versus bypass surgery. First, these trials must concen- Second Randomized Intervention Treatment of Angina trate on a well defined subset of patients, so many patients with (RITA II) (228), evaluated 1,018 patients with qualifying multivessel disease are excluded. To gain knowledge regarding conditions that did not necessitate bypass surgery or angio- a broader group of patients, observational studies will continue plasty who were randomized to an aggressive interventional to be important. approach or continued medical therapy. There was no survival The second drawback is ordinarily considered the major difference, and the number of repeat procedures remained strength of randomized trials, that is, any bias in the selection relatively low in both groups. The Veterans Affairs Non-Q- process is removed. However, physician bias (judgment) based Wave Infarction Strategies in Hospital (VANQWISH) study on features that are not easily measured may be predictive of randomized 920 patients with a non–Q wave myocardial outcomes. If that bias is correct, then patients who are infarction to early invasive or conservative treatment. There randomly selected will not have the benefit of any preexisting was no survival advantage for early invasive therapy (229). The 74B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B results of these studies point to the fact that patients without Interventional Therapy in severe ischemic syndromes and with predominantly single- Myocardial Infarction vessel disease cannot expect an improvement in survival with angioplasty but may have some decrease in angina threshold. Interventional procedures have also been found useful in Most important, the initial medical management of these three situations after acute myocardial infarction: 1) as an patients can be carried out safely. Additional trials extending elective procedure to alleviate ischemia resulting from a this concept of vigorous medical management have been remaining stenosis after an incomplete myocardial infarction; suggested. In one such proposed trial, comprehensive medical 2) as rescue therapy in patients who have ongoing or recurrent management will be tested, including extremely vigorous at- symptoms in the hours or days after thrombolytic therapy; and tempts at optimizing serum lipid levels. With this medical 3) in the acute phase as an alternative to thrombolytic therapy. management in place, patients will be randomized to a revas- Early investigations of patients undergoing angioplasty who cularization strategy using interventional means or continued had received thrombolytic therapy were begun by Jurgen medical therapy. Support is being provided by the NIH, the Meyer et al. (231), and later work was instituted by Hartzler et Canadian government, the VA system and industry. It will be al. (232) as an alternative to thrombolytic therapy in the acute very important in demonstrating the added value of interven- phase of myocardial infarction. tions in the era of effective secondary prevention. End points Trials were performed to evaluate the advantage of the use will include, in addition to survival, freedom from clinical of angioplasty after thrombolytic therapy (233–235). No ad- events, quality of life, functional status and economic consid- vantage could be found with this aggressive approach, but in erations. the much-quoted Thrombolysis in Myocardial Infarction The most important subset studied in the BARI trial was (TIMI)-II trial, angioplasty was used only in arteries that had patients with diabetes mellitus, who had a superior outcome been opened with thrombolysis; totally occluded arteries had when treated surgically. Conversely, patients without diabetes no intervention. The reverse strategy has been recently tested had identical results when treated medically or surgically. Of in a trial soon to be reported. In the Plasminogen Activator the diabetic patients receiving insulin or oral therapy, those Angioplasty Compatibility Trial (PACT) trial, patients were undergoing bypass surgery had an 80% survival rate at 5 years, studied who underwent thrombolytic therapy and then were whereas those randomized to angioplasty had a 65% 5-year transferred for early catheterization. In this trial, only occluded survival rate. A recent analysis of cardiac mortality in the arteries were opened, whereas arteries with TIMI grade 3 flow BARI study also shows significant excess cardiac mortality in had no intervention. Angioplasty in the chronic phase after the angioplasty group at 5 years; this difference can be myocardial infarction remained a matter for individual selec- completely accounted for by the patients with diabetes. The tion. The initial TIMI investigation of patients undergoing cardiac mortality rate in the diabetic patients treated with angioplasty within 18 to 48 h did not show improvement after surgery was 8% versus 24% in patients randomized to angio- use of the aggressive approach (236,237). plasty. There are several potential explanations for this differ- After thrombolytic therapy, many patients do not have ence. Diabetic patients are known to have more restenosis relief of angina or resolution of their electrocardiographic (230) and more progression of disease than are nondiabetic changes. Reperfusion after thrombolytic therapy occurs in patients. Likewise, the diabetic patients are less likely to ϳ55% to 85% of patients (238–240), and the mortality rate in perceive angina. These facts point to the necessity for careful those whose arteries do not reopen is high. In both the surveillance of diabetic patients, especially those who undergo Thrombolysis and Angioplasty in Myocardial Infarction less complete revascularization such as that provided by inter- (TAMI) 5 trial (241) and the Randomized Evaluation of ventional techniques. Of interest, diabetic patients receiving Salvage Angioplasty With Combined Utilization of Endpoints medical therapy in the EAST trial (n ϭ 59) did not have any (RESCUE) trial (242), the strategy of rescue angioplasty was difference in 5-year survival rates whether randomized to tested. Improved clinical results with angioplasty were demon- angioplasty or bypass surgery (90% in both groups). An strated in these two small trials. analysis of the baseline differences between the BARI and the Of most interest has been the use of angioplasty for acute EAST trial patients shows that the BARI trial patients had evolving myocardial infarction. Three trials that supported this somewhat more severe disease, but one other possibility for concept were reported simultaneously (243–246). The compos- the difference exists. The EAST trial patients had a protocol ite survival rate in the angioplasty group was superior to that in 1-year thallium scan and angiogram and again at 3 years. In the thrombolytic group. In the largest of these trials, Primary part because of this close surveillance, two thirds of the Angioplasty in Myocardial Infarction (PAMI) (244), the mor- angioplasty group diabetic patients underwent further revas- tality rate in the angioplasty group was 2.6% compared with cularization over the course of their observation. Again, tight 6.5% in the thrombolytic group (p ϭ 0.06). In these trials and surveillance and assurance of freedom from ischemia are the observational studies of primary angioplasty, the risk of probably wise in diabetic patients. Whether more careful intracerebral hemorrhage was reduced compared with throm- glycemic control will improve the outcome of diabetic patients bolytic therapy and is one of the major advantages of primary undergoing interventional and surgical revascularization is angioplasty, especially in older patients. soon to be investigated in the NHLBI-sponsored BARI II trial. Extrapolation of these results to a larger population was JACC Vol. 31, No. 4 Suppl B KING 75B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY investigated in the Global Use of Strategies to Open Occluded attempt to select patients who were uniquely suited for direc- Coronary Arteries in Acute Coronary Syndromes (GUSTO tional atherectomy and not suited for balloon angioplasty; IIb) trial (247). Although the difference between primary therefore, the failure to show any improvement over balloon angioplasty and accelerated tissue-type plasminogen activator angioplasty may have been due in part to the broad selection thrombolytic therapy in that study was small, there have been criteria. However, there were some positive aspects. The no studies suggesting that primary angioplasty carries a higher CAVEAT trial did show improved restenosis rates for a subset risk than thrombolytic therapy. of lesions in the LAD that did not include the ostium (257) but It seems clear from these observations that primary angio- not in other locations. In contrast, directional atherectomy was plasty can be performed with equivalent safety in patients with not shown to have a lower restenosis rate in the CCAT trial, acute evolving myocardial infarction. In centers dedicated to even in treatment of bulky proximal LAD lesions. this approach, superior results are usually achieved. However, I believe the directional atherectomy device still has prom- the most important elements in myocardial salvage are time to ise for certain unique situations, such as the bifurcation of reperfusion and establishment of adequate flow. Therefore, large coronary vessels in which the disease involves both thrombolytic therapy should not be delayed when immediate branches, particularly the flow divider. One drawback of angioplasty is not available. Ongoing investigations will test the atherectomy may have been the failure to remove adequate potential added advantage of combining thrombolysis and amounts of tissue. The BOAT trial (256) used a more vigorous antiplatelet therapy and will investigate whether the adverse technique for removal of tissue, followed by balloon dilation to effect of immediate angioplasty is still present in the era of achieve the largest possible posttreatment lumen. In that study powerful antiplatelet agents. The large multicenter trial PAMI and in an earlier pilot trial (258), long-term results showed Stent is completing its recruitment phase. Results of this trial greater improvement than those for the CAVEAT trial. The should establish whether the addition of stenting to balloon BOAT trial, in which patients were randomized to balloon angioplasty in the setting of acute myocardial infarction can angioplasty or optimal atherectomy, resulted in a restenosis further improve outcome. rate at 6 months of 40% in the balloon group and 32% in the atherectomy group. Despite this improved restenosis rate, atherectomy is seldom used in most centers because of 1) a New Devices higher non–Q wave infarction rate; 2) a higher cost; 3) a more Although the balloon remained the primary device for tedious and time-consuming procedure; and 4) a perceived performing angioplasty, by the late 1980s new equipment superior outcome in most lesions with stenting. However, began to emerge. The first of these was the directional future potentials for directional atherectomy should not be atherectomy device developed by John Simpson. The concept ignored. A project to combine intravascular ultrasound with was based on the idea that actual removal of atherosclerotic the atherectomy device was very intriguing because it would tissue would be superior to compression or dilation of the allow very complete tissue removal with the safety of removing artery. This device was used extensively during its preclinical only abnormal plaque tissue without damage to the deep wall and postmarketing approval phase for lesions that were judged structures. Recent observations by Antonio Colombo (person- to have a poor outcome with the use of balloon angioplasty; al communication, 1997) suggest that directional atherectomy these included aorto-ostial lesions, those with a great deal of followed by stenting may result in a very low restenosis rate. bulky plaque material in large vessels, protected left main Although this is a time- and resource-intensive procedure, it disease (248), bifurcation lesions (249,250) and arteries con- warrants further investigation. taining thrombus and plaque material remaining after balloon Directional atherectomy in saphenous vein grafts was eval- angioplasty. Lesions that had a significant amount of calcifica- uated in the CAVEAT II trial. Three hundred five patients tion on the lumen aspect of the artery proved not to be suitable were randomized to balloon angioplasty or directional atherec- for this technique (251). This device was also the first to tomy, and although there was greater lumen improvement undergo extensive clinical trials against balloon angioplasty, initially with atherectomy, the restenosis rates were not signif- including the Coronary Angioplasty Versus Excisional icantly different (45.6% for atherectomy, 50.5% for angio- Atherectomy Trial (CAVEAT) (252) CAVEAT II (a vein graft plasty). There was less target vessel revascularization in the study) (253) and the Canadian Coronary Atherectomy Trial atherectomy group, but in an unblinded trial this finding is (CCAT) (254). None of these trials showed directional difficult to interpret. There were also more Q wave myocardial atherectomy to be superior to balloon angioplasty in reducing infarctions in the atherectomy group (259). restenosis; in fact, acute complications, primarily non–Q wave The second atherectomy device to gain approval was the myocardial infarction, were increased with this technique. transluminal extraction catheter (TEC). This device, designed One-year follow-up of the CAVEAT trial showed a surprising to circumferentially remove tissue, especially thrombotic and excess of deaths in the atherectomy arm, but there was no other friable material, has been used largely in old, degener- relation with postprocedural myocardial infarction (255). As ated vein grafts (260–263). Because of the selection of high yet, there is no explanation for this finding, and a subsequent risk thrombotic lesions, complication rates with this device trial (Balloon versus Optimal Atherectomy Trial [BOAT]) have been relatively high (245). At some sites, TEC atherec- (256) has not shown similar results. In these trials, there was no tomy has been used to remove thrombus in the setting of acute 76B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B myocardial infarction, and good results have been reported. (276,277), undilatable lesions, total occlusions, calcification le- Lesions not associated with acute infarction that were more sions, long lesions and saphenous vein graft disease (278,279). complex did not seem to show improvement (264,265). Some lesions are generally contraindicated for laser therapy The rotational atherectomy device, which was developed by and may result in dissections or perforations, such as those in David Auth, was designed to selectively ablate firm, fibrotic very tortuous segments at the site of bends and those that are and calcific tissue (266–268). This device spins at a high rate of severely calcified, contain a significant amount of thrombus or speed of 150,000 to 200,000 rpm so its diamond-coated burr are located at the site of wide bifurcations (280–285). Reste- can abrade tissue by a mechanism similar to a dental drill. This nosis after laser angioplasty was found to be related to the final device has proved invaluable in the small subset of patients lumen diameter at the completion of the procedure (268,286). whose arteries will not open with balloon angioplasty and has Two new applications for laser therapy may be beneficial: 1) resulted in full expansion of arteries, allowing more precise for diffuse restenosis within stents, which is being evaluated in stent expansion in other hard, calcific lesions. The device has the Laser Angioplasty for Restenosed Stents (LARS) trial; and also been used extensively in lesions with superficial calcium 2) use of a very small fiber bundle, referred to as a laser wire, and those that are excessively long. Perhaps more than any for crossing chronic totally occluded segments (287). This wire other device, successful use is extremely operator dependent. is being evaluated in the Total Occlusion Trial With Angio- Differential cutting depends on very slow movement of the plasty by Using Laser Guidewire (TOTAL) trial (287), which burr through the lesion so excessive pressure is not applied has shown in the first 110 patients treated that the success rate against the plaque. This generates small particles about the with guidewire attempts was only ϳ40%, whereas the use of size of red blood cells that are removed by the reticuloendo- the laser with or without the guidewire attempts resulted in a thelial system. More vigorous advancement produces larger success rate of ϳ60% (Martin Leon, personal communication, bits of tissue that may produce microcirculatory obstruction. If 1997). the burr is tightly engaged into an unyielding lesion, it may Whereas the advent of new devices was greeted with a great result in rotational torsion, which could produce dissection. deal of enthusiasm in the late 1980s and 1990s, a comparison of Nonetheless, when used properly, acute outcomes have been the New Device for Angioplasty Registry collected between encouraging. Unfortunately the studies that have been done so 1990 and 1994 and the NHLBI balloon angioplasty registry of far, particularly the Excimer Laser, Rotablator and Angio- 1985 to 1986 proved very interesting. These registries were plasty Comparison (ERBAC) trial, comparing rotational both sponsored by the NHLBI, with the same core laboratory atherectomy with balloon angioplasty, have not shown an performing the data analysis. There were many baseline dif- improved restenosis rate (261,269–271). The ERBAC trial, ferences between the patients treated with the new devices and while not showing a significant difference in restenosis between those treated with balloons 5 to 7 years earlier. However, after rotary ablation and the balloon, actually resulted in a higher risk adjustment, overall improvement in 1-year outcome could revascularization rate in the rotary ablation group (42% vs. not be demonstrated with the new devices. In fact, target lesion 32% for the balloon group). A new trial of 500 patients, the revascularization was actually superior in the patients treated Comparison of Balloon Angioplasty Versus Rotational with balloon angioplasty. Many of the devices produced higher Atherectomy (COBRA) trial, also resulted in a higher resten- acute complication rates without improving late results. The osis rate in the rotary ablation group. The recently completed major weakness of this comparison is that only ϳ10% of the Study to Determine Rotational and Transluminal Angioplasty patients underwent stenting for elective indications. In that Strategy (STRATAS) trial will evaluate the strategy of tradi- one group, target lesion revascularization was less than that in tional rotary ablation in one group using burrs with a ratio to the balloon angioplasty group (288). the reference artery of Ͼ0.7, followed by standard balloon inflation, a group of patients undergoing more vigorous rotary ablation, taking the burr/balloon ratio up to ϳ0.8, followed by Stent Era very minimal balloon inflation. Coronary stenting has become the most important devel- Laser angioplasty has had a difficult time making inroads opment in interventional cardiology since the development of into interventional cardiology. There was enormous enthusi- the balloon and the steerable guidewire systems. At present, asm for laser therapy in the late 1980s, and companies sprang coronary stents are being used in between 25% and 75% of all up utilizing both excimer laser and homium yttrium-aluminum- interventional procedures and in some practices even more garnet (YAG) laser energy (272–274). frequently. These energies are transported down a flexible fiberoptic Stents are endoprosthetic scaffolding devices designed to bundle catheter and ablate tissue by direct tissue contact at the enlarge the vessel lumen, seal dissections and create a rounder, end of the fiber bundle. When activated, the laser ablates tissue smoother channel. The idea of an endoprosthetic scaffold is by vaporization and by shock waves. The ERBAC trial (269,275) very old. Alexis Carrel suggested the possibility of an endo- did not show any advantage for laser with regard to restenosis prosthetic device, and Charles Dotter developed “sleeve” graft rates. The cases treated in the NACI registry also suggested a devices but never implanted them in patients. The first human higher complication rate when this device was used (261). None- implants of coronary stents occurred in 1986. The stent was the theless, the laser catheter was used for aorto-ostial lesions interwoven helical self-expanding design (Wallstent), which JACC Vol. 31, No. 4 Suppl B KING 77B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY was used by Jaques Puel in Toulouse, France and Ulrich acute thrombosis rates, reduced bleeding complications and Sigwart in Lausanne, Switzerland. A wire coil stent, designed substantially shorter hospital stays, the practice of using anti- by Cesar Gianturco, was implanted at Emory University Hos- platelet therapy without continued anticoagulation and the use pital in 1987 by our group, and a slotted tube design by Julio of high pressure post-stent balloon expansion became standard Palmaz was inserted in a patient in Sao Paulo, Brazil by practice. These observations have now been confirmed by Richard Schatz and Eduardo Sosa the same year. clinical trials (Intracoronary Stenting and Antithrombotic Reg- Some of these stents were first applied to treat arteries that imen Trial [ISAR] [299] and STARS [300]). The STARS trial become acutely occluded after angioplasty. Others were in- resulted in a significant reduction in subacute thrombosis serted in an effort to reduce restenosis. Currently, more than (0.6%) in the aspirin and ticlopidine group compared with that 40 stent designs have been used worldwide, although until in the warfarin or aspirin therapy group. recently only two were available in the United States. The Although stents were evaluated in these trials for a rather Gianturco-Roubin stent, which was approved for general use narrow indication, the subsequent use pattern has shown that by the Food and Drug Administration (FDA) in 1993, was there is a widely held belief that stents will also be more indicated for abrupt and threatened closure (289–291). In effective than balloon angioplasty in many of the other subsets. 1994, the Palmaz-Schatz stent was approved by the FDA based Much of this remains unproved and needs additional evalua- on registry data (292,293) and two pivotal randomized trials. tion. One recent trial comparing stenting with balloon angio- Patients studied in the Stress Restenosis Study (STRESS) (294) plasty in vein grafts showed mildly improved clinical results and the Belgian Netherlands Stent Study (BENESTENT) (295) and restenosis rates utilizing the Palmaz-Schatz stent (Saphe- underwent single-lesion angioplasty in vessels ranging from 3 nous Vein De Novo [SAVED] trial) (301). Other evaluations to 4mm in diameter and Ͻ15 mm in length. The reduction in studying small vessels, long lesions and other subsets are restenosis was from 42% to 32% in the STRESS trial and from underway. 32% to 22% in the BENESTENT trial. Different quantitative Trials comparing second-generation stents with the Palmaz- angiographic systems may have been partially responsible for Schatz stent for general comparability regarding safety and the lower rates in the European study. After the general efficacy have also been conducted. Several of these designs are release of this stent, the device was used extensively for other soon to be released in the United States, and others will be indications, including long lesions requiring multiple stents, forthcoming in the near future. Improved methods for evalu- vessels Ͻ3 mm, bifurcation lesions, vein grafts and ostial and ating these stents in a consistent, cost-efficient manner are restenotic lesions. Although the STRESS and BENESTENT needed, and collaboration between the profession, the FDA trials showed a significant reduction in restenosis, bleeding and industry should significantly improve procedures in the complications were greater in the stent group. Over 3% of the future. Efforts to reduce the time to approval for safe devices patients with stents also experienced acute thrombotic occlu- are underway involving the American College of Cardiology, sion in the days after stent implantation despite extensive use the FDA and industry applicants. of heparin and Coumadin (warfarin) and a hospital stay that Issues to be resolved are the following: What evaluation averaged ϳ5 days. process should new but similar stents have before release? Two major developments revolutionized the use of stents. What role can standardized bench testing have? Can registry Paul Barragan and others in Marseilles, France began to use data demonstrating that a new stent can reach certain bench- antiplatelet therapy consisting of aspirin and ticlopidine exclu- marks for safety and restenosis suffice? Will off-label use be sively and abandoned the use of warfarin (296). This practice addressed? What role should industry play in supporting spread rapidly throughout France and other countries. Anto- expanded clinical investigation of stents in small vessels, long nio Colombo of Milan, Italy, who had invited Jonathan Tobis lesions, and so forth? Should evaluation of such anticipated from the University of California, Irvine to collaborate on an broader application of stents be part of original submissions? evaluation of the results of stenting judged by intravascular The cardiology community can contribute greatly to finding ultrasound, discovered that many times stents were not fully appropriate answers for these and other questions. These expanded and were in poor apposition against the vessel wall. conversations are ongoing. These features were not easily discernible by angiography, and Important questions regarding stenting remain. The first is this observation led to the use of high pressure post-stent whether stenting should be used in most lesions or whether it balloon inflations for more complete expansion of the devices should be limited to subsets in which it is demonstrated to be (297). An understanding of the improved results with anti- preferable to other techniques regarding outcomes. An obser- platelet therapy was supplied by Schoemig et al. (298). This vation from the BENESTENT trial was that patients under- study, comparing aspirin and ticlopidine therapy with warfarin going balloon angioplasty with excellent results did not have a therapy, demonstrated that the platelet activation occurring significantly higher restenosis rate than patients receiving with the latter was not present when antiplatelet therapy alone stents (Serruys P, personal communication, March 1997). was used. This is the likely explanation for the improved Further economic analysis of these data suggests that stenting subacute thrombosis rate that has been seen in all published in the LAD may be cost-saving, whereas stenting in the right studies using antiplatelet therapy alone. Because of dramati- coronary artery may be more expensive than balloon angio- cally improved clinical results, consisting of decreased sub- plasty in the long run. The clinical trials of stenting have 78B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B concentrated on single lesions. However, a large proportion of Adjunctive Equipment and Therapies Used patients currently undergoing interventions have multivessel in Angioplasty disease. The previous trials comparing angioplasty with bypass A number of devices have been developed to aid in the surgery are now being repeated with the use of stents. Two evaluation of arteries, in selection of therapies and in perfor- trials have begun in Europe. The Artery Revascularization mance of the procedures. Prominent among these is intravas- Therapy Study (ARTS) and Stent or Surgery (SOS) trials are cular ultrasound, which can give an image of the arterial wall designed as strategy trials to evaluate patients with multivessel that is not available by angiography. Characteristics, such as disease randomized between interventional techniques, includ- lumen size and contour, amount of plaque, the true size of the ing the use of stents versus a strategy of direct bypass surgery. external dimension of the artery, and the presence and distri- End points will be similar to those in previous trials, such as bution of calcium deposits within the artery are readily ascer- EAST, BARI and CABRI, and will include death, myocardial tained. This technique is used in selecting patients for devices infarction and the necessity for repeat interventions. Whether such as rotary ablation when calcium is present, for sizing these trials can improve on the excess late reintervention in the balloons and stents and when evaluating the result of therapy stent arm remain to be seen. If stents reduce restenosis in a to decide whether further interventions are necessary. Al- large number of lesions, then an improvement should occur. though used extensively in some centers, ultrasound remains Because the type lesions that will be stented will not be limited an expensive addition to the armamentarium, and its added to those in the STRESS and BENESTENT trials, the degree of value is currently being evaluated (309–312). Fiberoptic an- improvement in restenosis rates cannot be anticipated. To the gioscopy can give accurate information regarding the presence extent that repeat interventions are driven by progression of of thrombus but is seldom used clinically. disease or incomplete revascularization, stenting will not alter Two methods of assessing the physiology of coronary flow the results. have been developed: 1) the Doppler flow wire, which can Meanwhile, many additional stents are soon to be approved record the velocity of blood flow in the coronary artery and and released in the United States. This will be a very important thereby establish whether lesions are impeding the flow of development because earlier stents were difficult to place in blood (313). Measurements across lesions can show increased many situations, and the availability of lower profile, more velocity and turbulence and, in combination with measure- flexible stents of varying lengths should improve results. Be- ments of the arterial dimension, can lead to assessment of flow. cause improved stents may allow for placement in more This technique has been validated against angiography and diffusely diseased arteries, it is possible that restenosis rates ultrasound examinations and has a potential future in assessing will actually go up, and therefore the value of continued borderline lesions and guiding therapy. 2) Direct coronary progressive clinical evaluation cannot be overemphasized. pressure measurement can be performed with balloon cathe- The major drawback of stents at the present time is the ters, but the bulk of the catheter adds artifact to the measure- occurrence of neointimal proliferation and matrix formation ment. Studies from our group (314,315) showed that the within the stent (302–304). Although the restenosis rate may gradient was an important predictor of acute results and be reduced by stenting, if restenosis does occur it is a much restenosis. Recently, small-bore fluid-filled guidewires have more serious consequence than restenosis developing in a been developed, and catheter-tipped manometers on guide- wires as small as 0.014 in. allow accurate measurements of segment that has not been stented. In-stent restenosis has pressure across coronary stenoses (316). The use of direct carried a re-restenosis rate that has been variously reported as pressure measurements and velocity determinations during ranging between 25% and 65%. Techniques for treating in- maximal pharmacologic vasodilation allow assessment of the stent restenosis, including debulking with laser or Rotablator degree of coronary flow impairment, which may not be ob- and restenting residual disease, have been advocated by some. tained by angiography alone. These techniques undoubtedly One series primarily using balloon angioplasty was associated will be refined and should be helpful for management of with a relatively low repeat intervention rate (305), but few patients in the future. have been able to duplicate this experience. An important The most interesting pharmacologic adjunct to angioplasty determinant of the results of angioplasty for in-stent restenosis has been the introduction of potent antiplatelet agents, in seems to be the diffuseness of the restenotic process. Endovas- particular, the glycoprotein IIb/IIIa blockers. Compounds that cular brachytherapy was recently reported by Teirstein et al. are antibodies, peptides or small molecule nonpeptides have (306). In a group of 53 patients with in-stent restenosis been developed, and one (abciximab), a C7E3 antibody frag- randomized to repeat dilation with or without endovascular ment, has been released for clinical use. This drug, tested in brachytherapy, the group with active treatment had a signifi- patients with a recent myocardial infarction and unstable cantly reduced restenosis rate and late loss in lumen diameter. angina pectoris, has shown significant reduction in acute These studies used gamma irradiation and are being repeated ischemic complications (317,318). Other nonantibody drugs by others using the safer beta irradiation (307,308). Positive (tirofiban and integrilin) have also shown similar effects in results may allow radiation therapy to be delivered safely trials (319,320). None of the IIb/IIIa trials confirm any effect during routine catheterization procedures. on restenosis, but the effect on reducing acute thrombotic JACC Vol. 31, No. 4 Suppl B KING 79B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY complications has been impressive. Currently, these drugs of osteopontin and ␣V␤3 integrin expression (338), or the remain expensive, and the added value to heparin and less relation between ACE and apolipoprotein E genotypes with costly antiplatelet therapies remains to be elucidated. restenosis (339) or the prediction of restenosis based on the Because the role of platelets has been clearly defined in mitogenic activity of plasma (340) from assessment of blood interventional procedures, and these antiplatelet agents are samples taken at the time of coronary angioplasty. Fervent potent inhibitors of platelet aggregation, it would stand to activity using animal models parallels these clinical studies in reason that they will be important adjuncts. Cost is currently an effort to identify critical components of the restenosis the major constraint, and it is likely that costs will come down process that might be amenable to therapy. with competition among the agents. The clinical safety and Other advances, such as stents and atherectomy catheters, effectiveness of sustained antiplatelet activity are being evalu- have extended the horizons of arterial biologic research to ated in trials of oral IIb/IIIa compounds. Whether these will include biomaterials (in the case of stents) and the application alter the course of patients in the long term is of significant of histopathologic, immunohistochemical and molecular tech- interest. Will other compounds, such as specific antithrombins, niques, such as in situ hybridization and polymerase chain or less expensive agents, such as aspirin and ticlopidine, or the reaction to human tissue samples (obtained by directional newer agent clopidogril compete favorably? The newest play- atherectomy). Examples of studies in which atherectomy sam- ers in the antithrombotic competition involve blocking the ples have been used include investigations on the role of tissue factor pathway. The development and testing of these cytomegalovirus and its influence on the tumor suppressor agents will continue to link interventional cardiology and protein p53 (341) ostepontin expression (342) and cell prolif- hematology in productive investigation. Another contributor eration, apoptosis and histopathologic mechanisms of in-stent to platelet activation is the use of nonionic contrast agents restenosis (343). Furthermore, the fields of localized drug (321). We believe that nonionic contrast agents should be therapy, polymer chemistry, genetic engineering and brachy- avoided when possible to reduce the incidence of thrombotic therapy have recently gained an influx of inquisitive physicians complications (322,323). and scientists who have begun to apply the expertise gained in these disciplines to the field of arterial interventional therapy (344–347). Contribution of Coronary Angioplasty to There is a growing body of evidence that reactive oxygen species (oxygen-derived free radicals) are implicated in the Vascular Cell and Molecular Biology pathogenesis of restenosis. Several animal studies have dem- The phenomenon of vascular healing in response to me- onstrated that administration of antioxidants (radical scaven- chanical injury was investigated well before the advent of gers) in pigs decreases neointimal formation and increases coronary angioplasty. Early studies attempted to mimic the overall lumen and vessel size after coronary artery balloon spontaneous intimal lesions of arteriosclerotic disease by var- angioplasty (160,348,349). A recent study demonstrated that ious means, including endoluminal placement of sutures (324– increased superoxide production 2 weeks after balloon injury 326), adventitial electrocautery (326,327), ligation (328) and, in the same model was inhibited by administration of antioxi- later, embolectomy catheter deendothelialization (329–331). dant vitamins (350). Finally, a recent small clinical study These essential and groundbreaking studies defined the mor- demonstrated a benefit of the antioxidant probucol for reduc- phology, time course and basic pathologic mechanisms of ing restenosis (351). arterial wound healing, including determinations and condi- Diverse scientific disciplines have made major contributions tions of platelet and fibrin accumulation, inflammation, to the practice of angioplasty. However, it is the prevalence of smooth muscle cell proliferation, reendothelialization and restenosis as well as the sheer numbers of patients undergoing intimal lesion formation. Because so many of these studies coronary angioplasty for symptomatic ischemic coronary artery pointed to the similarities of “spontaneous” atherosclerotic disease that has driven and continues to drive the research disease with the mechanical loss of endothelium, the “response efforts of many investigators who are exploring the basic to injury” hypothesis of atherosclerosis was formed, which mechanisms of vascular biology in search of new therapies. remains a central tenet of the way in which coronary and peripheral arterial lesion formation is viewed (332). The work of Keith Robinson and his team in our research laboratory has The Discipline of Interventional Cardiology long convinced me that restenosis after angioplasty is a wound- Initially, balloon angioplasty was available only to those healing phenomenon (100). who would commit to recording data and cooperating with More recently, the field of vascular biology has fairly national registries. Later, the technique became available to all exploded with vast accumulations of information, much of it a cardiologists who wished to apply it in their patients. In 1988 consequence of new molecular techniques to identify, se- and again in 1993, the American College of Cardiology issued quence and target certain genes, genetic messages or protein guidelines on indications for coronary interventions (76,352). products that influence the milieu of an injured and healing Included in those guidelines were recommendations for ap- artery (333–337). For example, recent studies of patients proximate activity levels considered necessary to achieve and undergoing angioplasty have included explorations of the roles maintain competence. These recommendations have been 80B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B controversial, and recently a number of studies have been number of procedures. It is important to point out that performed to try to identify the relation between operator certification of this sort does not imply credentialling at the activity and outcomes (353–355). New recommendations are hospital level. Credentialling entitles one to practice. Certifi- being generated based on this and other evidence in an effort cation is a recognition of satisfactory completion of training to improve outcomes. However, credentialling to perform and an examination and is designed to recognize that achieve- interventional procedures is entirely a local matter to be ment. determined by the hospital in which one practices. Many have Specific requirements for sitting for the examination are discovered that consolidation of experience among smaller being developed by the ABIM for the first examination to be numbers of operators within groups has been an effective given in late 1999. The American College of Cardiology and strategy. This achieves a higher level of experience, which is the Society for Cardiac Angiography and Interventions are necessary as interventional procedures become more and more developing a joint board review course to assist in preparation complex and the knowledge of new innovations becomes for this examination. critical. The participation in the selection of interventional procedures by colleagues who do not perform these techniques can also be helpful in diffusing the concern about self-referral. Conclusions A quick solution to the problem of an oversupply of operators Interventional cardiology has sprung from its infancy performing angioplasty is not immediately attainable, but there through a turbulent adolescence and is now approaching is pressure to consolidate and improve quality. Undoubtedly, maturity. Because of dramatic technologic developments, heightened surveillance of performance of all medical proce- many patients can now undergo appropriate revascularization dures will be part of our future, and it is crucial that the procedures much less obtrusively than was possible in the past. profession participate to the greatest extent possible in devel- With this enhanced technologic prowess must come reasoned oping rational guidelines. judgment in the management of patients. A maturing disci- Much of the expanding knowledge base in interventional pline demands well trained, highly motivated and experienced cardiology is being developed through the mechanism of operators to fulfill its greatest potential. Innovations and new ongoing randomized clinical trials. Some of these will be discoveries are not completed but are just beginning. The structured to look at surrogate end points, such as restenosis science of vascular biology and its lessons are being learned by rates. However there is an increasing emphasis on clinical the interventional cardiologist. The potential for altering heal- outcomes, which is appropriate. Topol et al. (356) emphasized ing responses through an understanding of pharmacologic and some of the problems in clinical trial design in an excellent physical agents that act on genetic signals may change the review. They stressed the importance of death and myocardial interventionalist’s fixation on simply mechanical and geometric infarction as a robust end point for these trials. However, one improvements. In the final analysis, it will be patient outcomes should remember that coronary interventions seldom result in that determine the success of our efforts. These will not be death but often produce creatine kinase (CK) elevations determined by interventional cardiology in isolation but recorded as infarction. The evidence regarding the prognosis through application of appropriate therapies at the appropri- of CK elevations in the moderate range without Q waves, ate times, be they medical, interventional or surgical. Perhaps documented vessel reclosure or emergency surgery is still in the millenium to follow, this revolution in management of controversial, and much more information is needed before the world’s leading cause of death stimulated by Forssmann, combining these events with death as the reference standard. Cournand, Sones, Favaloro, Dotter, Gruentzig and many Carefully designed and executed randomized trials will be others will translate, through the efforts of our scientific necessary to answer many questions, and carefully controlled colleagues, to a solution for atherosclerosis itself. registries will be appropriate for others. The challenge will be to thoughtfully judge which method is sufficient and cost- effective. Because of the exploding knowledge base underlying the References discipline of interventional cardiology, the ABIM has ap- 1. Hurst JW. History of cardiac catheterization. In: King SB III, Douglas JS Jr, proved a certificate of added qualification (CAQ) in interven- editors. Coronary Arteriography and Angioplasty. New York: McGraw- Hill, 1985:1–9. tional cardiology. This will be the second such CAQ approved, 2. Forssmann W. The catheterization of the right side of the heart. Klin the other being for cardiac electrophysiology. The purpose of Wochenschr 1929;8:2085. the CAQ will be to recognize those who are bona fide 3. Forssmann W. Experiments on Myself: Memoirs of a Surgeon in Germany. practitioners and consultants in interventional cardiology and New York: St. Martin’s Press, 1974:84–5. 4. Klein O. Determining human cardiac output (minute volume) using Fick’s therefore will ultimately require completion of a minimum of principle (extraction of mixed venous blood by cardiac catheterization). 1 year of interventional cardiology training within an ABIM- Med Wochenschr 1930;77:1311. approved fellowship program. This training will be in addition 5. Cournand A, Ranges HA. Catheterization of the right auricle in man. Proc to the usual 3-year cardiology program. The examination will Soc Exp Biol Med 1941;46:462. 6. Cournand A, Riley RL, Bradley SE, et al. Studies of the circulation in initially also be open to those who have been actively engaged clinical shock. Surgery 1943;13:964. in interventional cardiology and have performed a substantial 7. Brannon ES, Weens HS, Warren JW. Atrial septal defect: Study of JACC Vol. 31, No. 4 Suppl B KING 81B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY

hemodynamics by the technique of right heart catheterization. Am J Med transluminal coronary angioplasty: the early Zurich experience. J Am Coll Sci 1945;210:480. Cardiol 1993;22:353–60. 8. Stead EA, Warren JV, Merrill AJ, Brannon ES. The cardiac output in male 36. Meier B, Gruentzig AR, King SB III, et al. Risk of side branch occlusion subjects as measured by the technique of right atrial catheterization: during coronary angioplasty. Am J Cardiol 1984;53:10–4. Normal values with observations on the effect of anxiety and tilting. J Clin 37. King SB III, Douglas JS, Gruentzig AR. Percutaneous transluminal coro- Invest 1945;24:326. nary angioplasty. In: King SB III, Douglas JS, editors. Coronary Angiog- 9. Warren JV, Stead EA. Fluid dynamics in chronic congestive heart failure: raphy and Angioplasty. New York: McGraw-Hill, 1985:433–60. An interpretation of the mechanisms producing the edema, increased 38. Carr MK. The use of the guiding catheter in coronary angioplasty: the plasma volume and elevated venous pressure in certain patients with technique of manipulating catheters to obtain the necessary power to cross prolonged congestive failure. Arch Intern Med 1944;73:138. tight coronary stenoses. Cathet Cardiovasc Diagn 1986;12:189–97. 10. Zimmerman HA, Scott RW, Becker NO. Catheterization of the left side of 39. Newton CM, Lewis SA, Vetrovec GW. Technique for guiding catheter the heart in man. Circulation 1950;1:357. exchange during coronary angioplasty while maintaining guidewire access 11. Baltaxe HA, Amplatz K, Levin DC. Coronary Angiography. Springfield, across a coronary stenosis. Cathet Cardiovasc Diagn 1986;15:173–5. Charles C Thomas, 1976. 40. Kulick DL. Use of the internal mammary artery guiding catheter for 12. Moniz E, DeCarvalho L, Lima A. Angiopneumographie. Presse Med percutaneous transluminal coronary angioplasty of the shepherd’s crook 1931;39:996. right coronary artery. Cathet Cardiovasc Diagn 1989;16:190–2. 13. Reboul H, Racine M. La ventriculographie cardiaque experimentale. 41. Arani DT, Bunnell IL, Visco JP, Conley JG. Double loop guiding catheter: Presse Med 1933;1:763. A primary catheter for angioplasty of the right coronary artery. Cathet 14. Radner S. An attempt at the roentgenologic visualization of the coronary Cardiovasc Diagn 1988;15:125–31. blood vessels in man. Acta Radiol 1945;26:497. 42. Douglas JS Jr, King SB III. Pathoanatomy of the coronary arteries. In: King 15. DiGuglielmo L, Guttaduro M. Roentgenologic study of coronary arteries in SB III, Douglas JS, editors. Coronary Arteriography and Angioplasty. New living. Acta Radiol Suppl (Stockh) 1952;97. York: McGraw-Hill, 1985:86–121. 16. Dotter CT, Frische LH. Visualization of the coronary circulation by 43. Meier B, Gruentzig AR, Dekmezian RH, Brown JE. Percutaneous perfu- occlusion aortography: a practical method. Radiology 1958;76:502. sion of occluded coronary arteries with blood from the femoral artery: A 17. Arnulf G, Chacornac R. Communication to La Societe de Chirurgie de dog study. Cathet Cardiovasc Diagn 1985;11:81–7. Lyon, November 14, 1957, in Arnulf G: L’arteriographie methodique des 44. Hopf R, Kunkel B, Schneider M, Kaltenbach M. Koronarperfusion bei arteres coronaires grace a l’utilisation de l’acetylcholine: Donnees experi- akutem Gefassverschluss im Rahmen der transluminalen Koronarangio- mentales et cliniques. Bull Acad Natl Med (Paris) 1958;25/26:661. plastick (TCA). Z Kardiol 1985;74:580–4. 18. Richard LS, Thal AP. Phasic dye injection control system for coronary 45. Angelini P, Heibig J, Leachman DR. Distal hemoperfusion during percu- arteriography in the human. Surg Gynecol Obstet 1958;107:739. taneous transluminal coronary angioplasty. Am J Cardiol 1986;58:252–5. 19. Bellman S, Frank HA, Lambert PB, Littman D, Williams JA. Coronary 46. Hinohara T, Simpson JB, Phillips HR, et al. Transluminal catheter reper- arteriography: I. Differential opacification of the aortic stream catheters of fusion: a new technique to reestablish blood flow after coronary occlusion special design: Experimental development. N Engl J Med 1960;262:325. during percutaneous transluminal coronary angioplasty. Am J Cardiol 20. Nordenstrom B. Contrast examination of the cardiovascular system during 1986;57:684–6. increased intrabronchial pressure. Acta Radiol Suppl (Stockh) 1960;200 47. Busch U, Erbel R, Clas W, et al. Verbesserete Okklusionstoleranzzeit Suppl:110. durch kontinuierliche Koronarperfusion mit modifiziertem. Gruentzig- 21. Bilgutay AM, Gannon P, Sterns LP, Ferlic R, Lillehei CW. Coronary Koronarangioplastiekatheter. Z Kardiol 1985;74:435–9. arteriography: New method under induced hypotension by pacing— 48. Erbel R, Rupprecht HJ, Busch U, et al. Continuous coronary perfusion and experimental and clinical application. Arch Surg 1964;89:899. prolonged balloon inflation during stenosis dilatation. Z Kardiol 1987;76: 22. Sones FM Jr. Coronary arteriography. Read before the Eighth Annual 49–52. Convention of the American College of Cardiology, Philadelphia, 1959. 49. Stack RS, Quigley PJ, Collins G, Phillips HR III. Perfusion balloon catheter. Am J Cardiol 1988;61:77G–80G. 23. Favaloro RG. Critical analysis of coronary artery bypass grafting: a 30-year journey. J Am Coll Cardiol 1998;31:1B–63B. 50. Quigley PJ, Hinohara T, Phillips HR, et al. Myocardial protection during coronary angioplasty with an autoperfusion balloon catheter in humans. 24. Garrett HE, Dennis EW, DeBakey ME. Aorto coronary bypass with Circulation 1988;78:1128–34. saphenous vein graft. JAMA 1973;223:792–4. 51. Sundram P, Harvey JR, Johnson RG, Schwartz MJ, Baim DS. Benefits of 25. Johnson WD, Flemma RJ, Lepley D Jr, et al. Extended treatment of severe the perfusion catheter for emergency coronary artery grafting after failed coronary artery disease: a total surgical approach. Ann Surg 1969;170:460– percutaneous transluminal coronary angioplasty. Am J Cardiol 1989;63: 70. 282–5. 26. Green GE, Stertzer SH, Reppert EH. Coronary arterial bypass grafts. Ann 52. Talley J, Weintraub W, Anderson H, et al. Late clinical outcome of Thorac Surg 1968;5:443–50. coronary bypass surgery after failed elective PTCA [abstract]. Circulation 27. Dotter CT, Judkins MP. Transluminal treatment of arteriosclerotic obstruc- 1987;76 Suppl IV:IV-352. tion: Description of a new technique and preliminary report of its applica- 53. Page US, Okies JE, Colburn LQ, Bigelow JC, Salomon NW, Krause AH. tion. Circulation 1964;30:654. Percutaneous transluminal coronary angioplasty: a growing surgical prob- 28. Dotter CT, Rosch J, Judkins MP. Transluminal dilatation of arteriosclerotic lem. J Thorac Cardiovasc Surg 1986;92:847–852. stenosis. Surg Gynecol Obstet 1968;127:794. 54. Murphy DA, Craver JM. Emergency bypass surgery of patients undergoing 29. Porstmann W. Ein neuer Korsett-Ballonkatheter zur transluminalen Reka- percutaneous coronary angioplasty. In: Jang GD, editor. Angioplasty. New nalisation nach Dotter unter besonderer Berucksichtigung von Oblitera- York: McGraw-Hill, 1985:357–367. tionen an den Beckenarterien. Radiol Diagn 1973;14:239–43. 55. Van Tassel, RA, Gobel FL, Rydell MA, Vlodaver Z, MacCarter DJ. A less 30. Wierny L, Plass R, Porstmann W. Long-term results in 100 consecutive traumatic catheter for coronary arteriography. Cathet Cardiovasc Diagn patients treated by transluminal angioplasty. Radiology 1974;112:543. 1985;11:187–99. 31. Zeitler E, Schoop W, Zahnow W. The treatment of occlusive arterial 56. Meier B. Kissing balloon coronary angioplasty. Am J Cardiol 1984;54:918– disease by transluminal catheter angioplasty. Radiology 1971;99:19–26. 920. 32. King SB III. Angioplasty from bench to bedside to bench. Circulation 57. Zack PM, Ischinger T. Experience with a technique for coronary angio- 1996;93:1621–9. plasty of bifurcational lesions. Cathet Cardiovasc Diagn 1984;10:433–43. 33. Gruentzig A, Turina M, Schneider J. Experimental percutaneous dilatation 58. Pinkerton CA, Slack JD, van Tassel JW, Orr CM. Angioplasty for dilatation of coronary artery stenosis [abstract]. Circulation 1976;54 Suppl:81. of complex coronary artery bifurcation stenoses. Am J Cardiol 1985;55: 34. Gruentzig AR, King SB, Schlumpf M, Siegenthaler W. Long term followup 1626–8. after percutaneous transluminal coronary angioplasty: the early Zurich 59. Oesterle SN, McAuley BJ, Buchbinder M, Simpson JB. Angioplasty at experience. N Engl J Med 1987;316:1127–32. coronary bifurcations: single-guide, two-wire technique. Cathet Cardiovasc 35. King SB III, Schlumpf M. Ten-year completed follow-up of percutaneous Diagn 1986;12:57–62. 82B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B

60. George BS, Myler RK, Stertzer SH, et al. Balloon angioplasty of coronary following percutaneous transluminal coronary angioplasty. Ann Thorac bifurcation lesions: the kissing balloon technique. Cathet Cardiovasc Diagn Surg 1984;37:473–8. 1986;12:124–38. 83. Thornton MA, Gruentzig AR, Hollman J, King SB, Douglas JS. Coumadin 61. Hartzler GO. Three-wire technique: a unique approach to percutaneous and aspirin in prevention of recurrence after transluminal coronary angio- transluminal coronary angioplasty of a trifurcation lesion. Cathet Cardio- plasty: A randomized study. Circulation 1984;69:721–7. vasc Diagn 1987;13:174–7. 84. Meier B, King SB, Gruentzig AR, et al. Repeat coronary angioplasty. J Am 62. Nath A, Vetrovec GW, Cowley MJ, et al. Double-wire angioplasty of the Coll Cardiol 1984;4:463–6. right coronary artery bifurcational stenosis. Cathet Cardiovasc Diagn 85. Holmes DR Jr, Vlietstra RE, Smith HC, et al. Restenosis after percutane- 1988;14:37–40. ous transluminal coronary angioplasty (PTCA): A report from the PTCA 63. Thomas ES, Williams DO. Simultaneous double balloon coronary angio- Registry of the National Heart, Lung and Blood Institute. Am J Cardiol plasty through a single guiding catheter for bifurcation lesions. Cathet 1984;53:77C–81C. Cardiovasc Diagn 1988;15:260–4. 86. Leimgruber PP, Roubin GS, Hollman J, et al. Restenosis after successful 64. Myler RK, McConanhay DR, Stertzer SH, et al. Coronary bifurcation coronary angioplasty in patients with single-vessel disease. Circulation lesions: the kissing balloon probe technique via a single guiding catheter. 1986;73/74:710–7. Cathet Cardiovasc Diagn 1989;16:267–78. 87. Kaltenbach M, Kober G, Scherer D, Vallbracht C. Recurrence rate after 65. Slack JD, Pinkerton CA. Complex coronary angioplasty: Use of extended successful coronary angioplasty. Eur Heart J 1985;6:276–81. and angled balloon catheters. Cathet Cardiovasc Diagn 1987;13:284–7. 88. Meyer J, Schmitz H, Kiesslich T, et al. Percutaneous transluminal coronary 66. Vivekaphirat V, Zapala C, Foschi AE. Clinical experience with the use of angioplasty in patients with stable and unstable angina pectoris: analysis of the angled-balloon dilatation catheter. Cathet Cardiovasc Diagn 1989;17: early and late results. Am Heart J 1983;106:973–80. 121–5. 89. Steffenino G, Meier B, Finci L, Rutishauser W. Followup results of 67. Kaltenbach M. The long-wire technique: a new technique for steerable treatment of unstable angina by coronary angioplasty. Br Heart J 1987;57: balloon catheter dilatation of coronary artery stenoses. Eur Heart J 416–9. 1984;5:1004–9. 90. Gruentzig A. Results from coronary angioplasty and implications for the 68. Bonzel T, Wollschlager H, Just H. Ein neues Kathetersystem zur mecha- future. Am Heart J 1982;103:779–82. nischen Dilatation von Koronarstenosen mit austauschbaren intrakor- onaren Kathetern, hoherem Kontrastmittelfluss und verbesserter Steuer- 91. Mabin T, Holmes DR Jr, Smith H, et al. Follow-up clinical results in barkeit. Biomed Techn 1986;31:195–200. patients undergoing percutaneous transluminal coronary angioplasty. Cir- 69. Bonzel TR, Wollschlager H, Meinertz T, Kaspar W, Just H. The sliding rail culation 1985;71:754–60. (Monorail) principle: description of a new technique and its application for 92. Liu MW, Roubin GS, King SB III. Restenosis after coronary angioplasty: coronary angioplasty. In: Vogel JHK, King SB III, editors. Interventional Potential biologic determinants and role of intimal hyperplasia. Circulation Cardiology: Future Directions. St. Louis (MO): CV Mosby, 1989:320–326. 1989;79:1374–87. 70. Finci L, Meier B, Roy P, Steffenino G, Rutishauser W. Clinical experience 93. Gravanis MB, Roubin GS. Histopathologic phenomena at the site of with the Monorail balloon catheter for coronary angioplasty. Cathet coronary angioplasty. Human Pathol 1989;20:477–85. Cardiovasc Diagn 1988;14:206–12. 94. Waller BF. Morphologic correlates of coronary angiographic patterns at the 71. Hasdai D, Bell MR, Grill DE, et al. Outcome Ն10 years after successful site of coronary angioplasty. Clin Cardiol 1988;11:817–22. percutaneous transluminal coronary angioplasty. Am J Cardiol 1997;79: 95. Johnson DE, Hinohara T, Selmon MR, Braden LJ, Simpson JB. Primary 1005–11. peripheral arterial stenoses and restenoses excised by transluminal atherec- 72. Talley JD, Hurst JW, King SB III, et al. Clinical outcome 5 years after tomy: Histopathologic study. J Am Coll Cardiol 1990;15:419–25. attempted percutaneous transluminal coronary angioplasty in 427 patients. 96. Waller BF, McManus BM, Gorfinkel J, et al. Status of major epicardial Circulation 1988;77:820–9. coronary arteries 80 to 150 days after percutaneous transluminal coronary 73. Mullin SM, Passamani ER, Mock MB. Historical background of the angioplasty: analysis of 3 necropsy patients. Am J Cardiol 1983;51:81–4. National Heart, Lung and Blood Institute Registry for Percutaneous 97. Waller BF, Pinkerton CA, Orr CM, Slack JD, VanTasssel JW. Two distinct Transluminal Coronary Angioplasty. Am J Cardiol 1984;53:3C–6C. types of restenosis lesions after coronary balloon angioplasty: intimal 74. Mock MB, Bentivoglio L, Dorros G, et al. NHLBI Interim Registry for proliferation and atherosclerotic plaques only: An analysis of 20 necropsy PTCA. Washington (DC): US Department of Health, Education, and patients [abstract]. Circulation 1990;82 Suppl III:III-314. Welfare: Publication No. (NIH):80:2030. 98. Austin GE, Ratliff NB, Hollman J, Tabei S, Phillips DF. Intimal prolifer- 75. Kent KM, Bentivoglio L, Block PC, et al. Percutaneous transluminal ation of smooth muscle cells as an explanation for recurrent coronary artery coronary angioplasty: Report from the NHLBI Registry. Am J Cardiol stenosis after percutaneous transluminal coronary angioplasty. J Am Coll 1982;49:2011–7. Cardiol 1985;6:369–75. 76. Ryan TJ, Faxon DP, Gunnar RM, et al. Guidelines for percutaneous 99. Schwartz RS, Murphy JG, Edwards WD, Camrud AR, Vlietstra RE, transluminal coronary angioplasty: a report of the American College of Holmes DR. Restenosis after balloon angioplasty: A practical proliferative Cardiology/American Heart Association Task Force on Assessment of model in porcine coronary arteries. Circulation 1990;82:2190–200. Diagnostic and Therapeutic Cardiovascular Procedures. J Am Coll Cardiol 100. Karas SP, Gravanis MB, Santoian EC, Robinson KA, Anderberg K, King 1988;12:529–45. SB III. Coronary intimal proliferation after balloon injury and stenting in 77. Bredlau CE, Roubin GS, Leimgruber PP, Douglas JS Jr, King SB III, swine: An animal model of restenosis. J Am Coll Cardiol 1992;20:467–74. Gruentzig AR. In-hospital morbidity and mortality in patients undergoing 101. Harker LA. Role of platelets and thrombosis in mechanisms of acute elective coronary angioplasty. Circulation 1985;72:1044–52. occlusion and restenosis after angioplasty. Am J Cardiol 1987;60:21B–8B. 78. Ellis SG, Roubin GS, King SB III, et al. In-hospital cardiac mortality 102. Adams PC, Badimon JJ, Badimon L, Chesebro JH, Fuster V. Role of following acute closure after percutaneous transluminal coronary angio- platelets in atherogenesis: Relevance to coronary arterial restenosis after plasty: analysis of risk factors from 8,207 procedures. J Am Coll Cardiol angioplasty. Cardiovasc Clin 1987;18:49–71. 1988;11:211–6. 103. Kohchi K, Takebayashi S, Block PC, Hiroki T, Nobuyoshi M. Arterial 79. Ellis SG, Myler RK, King SB III, et al. Causes and correlates of death after changes after percutaneous coronary angioplasty: results at autopsy. J Am unsupported coronary angioplasty: implications for use of angioplasty and Coll Cardiol 1987;10:592–9. advanced support techniques in high-risk settings. Am J Cardiol 1991;68: 104. Ueda M, Becker AE, Fujimoto T. Pathological changes induced by 1447–51. repeated percutaneous transluminal coronary angioplasty. Br Heart J 80. Whitworth HB, Roubin GS, Hollman J, et al. Effect of nifedipine on 1987;58:635–43. recurrent stenosis after percutaneous transluminal coronary angioplasty. 105. Block PC, Myler RK, Stertzer S, Fallen JT. Morphology after PTCA in J Am Coll Cardiol 1986;8:1271–6. human beings. N Engl J Med 1981;305:382–5. 81. Leimgruber PP, Robin GS, Anderson HV, et al. Influence of intimal 106. Farb A, Virmani R, Atkinson JB, Kolodgie FD. Plaque morphology and dissection on restenosis after successful angioplasty. Circulation 1985;72: pathologic changes in arteries from patients dying after coronary balloon 530–5. angioplasty. J Am Coll Cardiol 1990;16:1421–9. 82. Murphy DA, Craver JM, King SB. Distal coronary artery dissection 107. Bertrand ME, LaBlanche JM, Fourrier JL, Traisnel G. Percutaneous JACC Vol. 31, No. 4 Suppl B KING 83B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY

transluminal coronary angioplasty in patients with spasm superimposed on gradient measurements during percutaneous transluminal coronary angio- atherosclerotic narrowing. Br Heart J 1987;58:469–72. plasty. Circulation 1986;73:1223–30. 108. Bertrand ME, LaBlanche JM, Thieuleux FA, Fourrier JL, Traisnel G, 130. Nobuyoshi M, Kimura T, Nosaka H, et al. Restenosis after successful Asseman P. Comparative results of percutaneous transluminal coronary percutaneous transluminal coronary angioplasty: serial angiographic fol- angioplasty in patients with dynamic versus fixed coronary stenosis. J Am lowup of 229 patients. J Am Coll Cardiol 1988;12:616–23. Coll Cardiol 1986;8:504–8. 131. Meier B, Gruentzig AR, King SB, et al. Higher balloon dilatation pressure 109. Leisch F, Schutzenberger W, Kerschner K, Herbinger W. Influence of in coronary angioplasty. Am Heart J 1984;10:619–22. variant angina on the results of percutaneous transluminal coronary 132. Roubin GS, Douglas JS Jr, King SB III, et al. Influence of balloon size on angioplasty. Br Heart J 1986;56:341–5. initial success, acute complications, and restenosis after percutaneous 110. Ardissino D, Barberis P, de Servi S, et al. Abnormal coronary vasoconstric- transluminal coronary angioplasty: A prospective randomized study. Circu- tion as a predictor of restenosis after successful angioplasty in patients with lation 1988;78:557–65. unstable angina pectoris. N Engl J Med 1991;325:1053–7. 133. Sarembock IJ, La Veau PJ, Sigal SL, et al. The influence of inflation 111. Whitworth HB, Pilcher GS, Roubin GS, et al. Do proximal lesions involving pressure and balloon size on the development of intimal hyperplasia the origin of the left anterior descending artery (LAD) have a higher following balloon angioplasty: A study in the atherosclerotic rabbit. Circu- restenosis rate after coronary angioplasty (PTCA) [abstract]? Circulation lation 1989;80:1029–40. 1985;72:398. 134. Quigley PJ, Perez J, Mikat E, et al. Effective prolonged balloon inflation on 112. Piovaccari G, Fattori R, Marzocchi Z, Marrozzini C, Prati F, Magnani B. arterial hyperplasia in rabbits. Circulation 1986;4:184. Percutaneous transluminal coronary angioplasty of the very proximal left 135. Ellis SG, Roubin GS, Wilentz J, et al. Effect of 18- to 24-hour heparin anterior descending artery lesions: immediate results and follow-up. Int administration for prevention of restenosis after uncomplicated coronary J Cardiol 1991;30:151–5. angioplasty. Am Heart J 1989;117:777–82. 113. Ellis SG, Roubin GS, King SB III, Douglas JS Jr, Cox WR. Importance of 136. Urban P, Bulen N, Fox K, et al. Lack of effect of warfarin on the resenosis stenosis morphology in the estimation of restenosis risk after elective percutaneous transluminal coronary angioplasty. Am J Cardiol 1989;63: rate or on clinical outcome after balloon angioplasty. Br Heart J 1988;6: 30–4. 485–8. 114. Austin GE, Hollman J, Lynn MJ, Meier B. Serum lipoprotein levels fail to 137. Wilentz JR, Sanborn TA, Hauderschild CC, et al. Platelet accumulation in predict postangioplasty recurrent coronary artery stenosis. Cleve Clin experimental angioplasty. Circulation 1987;75:636–42. J Med 1989;56:509–14. 138. Barnathan ES, Schwartz JS, Taylor L, et al. Aspirin and dipyridamole in the 115. Hearn JA, Donohue BC, King SB III, et al. Does serum LP(a) predict prevention of acute coronary thrombosis complicating coronary angio- restenosis after PTCA [abstract]? J Am Coll Cardiol 1990;15 Suppl A:205A. plasty. Circulation 1987;76:125–34. 116. Plokker THW, Ernst SM, Bal ET, et al. Percutaneous transluminal 139. Schwartz L, Bourassa MG, Lesperance J, et al. Aspirin and dipyridamole in coronary angioplasty in patients with unstable angina pectoris refractory to the prevention of restenosis after percutaneous transluminal coronary medical therapy: Long-term clinical and angiographic results. Cathet angioplasty. N Engl J Med 1988;318:1714–9. Cardiovasc Diagn 1988;14:15–8. 140. Dehmer GJ, Popma JJ, Van den Berg EK, et al. Reduction in the rate of 117. Johansson SR, Ekstrom L, Emanuelsson H. Higher recurrence rate after early restenosis after coronary angioplasty by a diet supplemented with n-3 coronary angioplasty in unstable angina pectoris. Angiology 1991;42:273– fatty acids. N Engl J Med 1988;319:733–40. 80. 141. Reis GJ, Sipperly ME, Boucher TM, et al. Randomised trial of fish oil for 118. Luijten HE, Beatt KJ, de Feyter PJ, van den Brand M, Reiber JH, Serruys prevention of restenosis after coronary angioplasty. Lancet 1989;2:177–81. PW. Angioplasty for stable versus unstable angina pectoris: are unstable 142. Grigg LE, Kay TWH, Valentine PA, et al. Determinants of restenosis and patients more likely to get restenosis? A quantitative angiographic study in lack of effect of dietary supplementation with eicosapentaneoic acid on 339 consecutive patients. Int J Card Imaging 1988;3:87–97. incidence of coronary artery restenosis after angioplasty. J Am Coll Cardiol 119. Halon DA, Merdler A, Shefer A, Flugelman MY, Lewis BS. Identifying 1988;12:1073–8. patients at high risk for restenosis after percutaneous transluminal coronary 143. Milner MR, Gallino RA, Leffingwell A, et al. Usefulness of fish oil angioplasty for unstable angina pectoris. Am J Cardiol 1989;64:289–93. supplements in preventing clinical evidence of restenosis after percutane- 120. Williams DO, Gruentzig AR, Kent KM, Detre KM, Kelsey SF, To T. ous transluminal angioplasty. Am J Cardiol 1989;64:294–9. Efficacy of repeat percutaneous transluminal coronary angioplasty for 144. Bairati I, Roy L, Meyer F. Double-blind, randomized, controlled trial of fish coronary restenosis. Am J Cardiol 1984;53:32C–5C. oil supplements in prevention of recurrence of stenosis after coronary 121. Black AJ, Anderson HV, Roubin GS, Powelson SW, Douglas JS Jr, King angioplasty. Circulation 1992;85:950–6. SB III. Repeat coronary angioplasty: Correlates of a second restenosis 145. Nye ER, Ilsley CDJ, Ablett MB, et al. Effect of eicosapentaneoic acid on J Am Coll Cardiol 1988;11:714–8. restenosis rate, clinical course and blood lipids in patients after percutane- 122. Deligonul U, Vandormael M, Kern MJ, Galan K. Repeat coronary ous transluminal coronary angioplasty. Aust NZ J Med 1990;20:549–52. angioplasty for restenosis: Results and predictors of follow-up clinical 146. Pepine CJ, Hirshfeld JW, MacDonald RG, et al. A controlled trial of events. Am Heart J 1989;117:997–1002. corticosteroids to prevent restenosis after coronary angioplasty. Circulation 123. Steffenino G, Meier B, Finci L, Rutishauser W. Recurrence of stenosis after 1990;81:1753–61. first and repeat coronary angioplasty: clinical and angiographic followup. G 147. Stone GW, Rutherford BD, McConahay DR, et al. A randomized trial of Ital Cardiol 1987;17:473–8. corticosteroids for the prevention of restenosis in 102 patients undergoing 124. Vandormael MG, Deligonul U, Kern MJ, Kennedy H, Galan K, Chaitman repeat coronary angioplasty. Cathet Cardiovasc Diagn 1989;18:227–31. B. Restenosis after multilesion percutaneous transluminal coronary angio- 148. Waterfield MD, Scrace GT, Whittle N, et al. Platelet-derived growth factor plasty. Am J Cardiol 1987;60:44B–7B. is structurally related to the putative transforming protein p28sis of simian 125. Lambert M, Bonan R, Cote G, et al. Early results, complications and sarcoma virus. Nature 1982;304:35–9. restenosis rates after multilesion and multivessel percutaneous transluminal 149. Russell SB, Trupin KM, Rodriguez-Eaton S, et al. Reduced growth-factor coronary angioplasty. Am J Cardiol 1987;60:788–91. requirement of keloid-derived fibroblasts may account for tumor growth. 126. Hirshfeld JW Jr, Schwartz JS, Jugo R, et al. Restenosis after coronary Proc Natl Acad Sci USA 1988;85:587–91. angioplasty: A multivariate statistical model to relate lesion and procedure 150. Rab ST, King SB III, Roubin GS, Carlin S, Hearn JA, Douglas JS Jr. variables to restenosis. J Am Coll Cardiol 1991;18:647–56. Coronary aneurysms following stent placement: a suggestion of altered 127. Gibson CM, Kuntz RE, Nobuyoshi M, Rosnser B, Baim DS. Lesion-to- vessel wall healing in the presence of anti-inflammatory agents. J Am Coll lesion independence of restenosis after treatment by conventional angio- Cardiol 1991;18:1524–8. plasty, stenting, or directional atherectomy: Validation of lesion-based 151. Powell JS, Clozel JP, Muller RKS, et al. Inhibitors of angiotensin- restenosis analysis. Circulation 1993;87:1123–9. converting enzyme prevent myointimal proliferation after vascular injury. 128. Hermans WR, Rensing BJ, Kelder JC, de Feyter PJ, Serruys PW. Postan- Science 1989;245:186–8. gioplasty restenosis rate between segments of the major coronary arteries. 152. The MERCATOR Study Group. Does the new angiotensin converting Am J Cardiol 1992;69:194–200. enzyme inhibitor cilazapril prevent restenosis after percutaneous translu- 129. Anderson HV, Roubin GS, Leimgruber PP, et al. Transstenotic pressure minal coronary angioplasty? Results of the MERCATOR study: A multi- 84B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B

center, randomized, double-blind placebo-controlled trial. Circulation 176. Finci L, Meier B, de Bruyne B, Steffenino G, Divernois J, Rutishauser W. 1992;86:100–10. Angiographic follow-up after multivessel percutaneous transluminal coro- 153. Faxon DP, on behalf of the Multicenter American Research Trial with nary angioplasty. Am J Cardiol 1987;60:467–70. Cilazapril after Angioplasty to Prevent Transluminal Coronary Obstruction 177. Deligonul U, Vandormael MG, Kern MJ, Zelman R, Glan K, Chaitman and Restenosis (MARCATOR) Study Group. Effect of high dose BR. Coronary angioplasty: a therapeutic option for symptomatic patients angiotensin-converting enzyme inhibition on restenosis: final results of the with two or three vessel coronary disease. J Am Coll Cardiol 1988;11: MARCATOR study, a multicenter double-blind, placebo-controlled trial of 1173–9. cilazapril. J Am Coll Cardiol 1995;2:362–9. 178. Dorros G, Lewis RF, Mathiak LM. Percutaneous transluminal coronary 154. Moreau JP, DeFeudis FU. Pharmacologic studies of somatostatin and angioplasty in multivessel coronary disease patients: Short- and long-term somatostatin-analogues: Therapeutic advances and perspectives. Life Sci follow-up in single and multiple dilatations. Clin Cardiol 1988;11:601–12. 1987;40:419–37. 179. Ellis SG, Fisher L, Dushman-Ellis S, et al. Comparison of coronary 155. Weintraub WS, Boccuzzi SJ, Klein JL, et al. Lack of effect of lovastatin on angioplasty with medical treatment for single- and double-vessel coronary restenosis after coronary angioplasty. N Engl J Med 1994;331:1331–7. disease with left anterior descending coronary involvement: Long term 156. Yui Y, Kawai C, Hosoda S. Pravastatin (mevalotin) restenosis trial after outcome based on an Emory-CASS Registry Study. Am Heart J 1989;118: percutaneous transluminal coronary angioplasty: Cholesterol reduction 208–20. rate determines the restenosis rate. Ann N Y Acad Sci 1995;748:208–16. 180. Detre K, Holubkov R, Kelsey S, et al, and the Co-investigators of the 157. Foley DP, Serruys PW. Fluvastatin for the prevention of restenosis after NHLBI PTCA Registry. Percutaneous transluminal coronary angioplasty in coronary balloon angioplasty: angiographic and methodological back- 1985–1986 and 1977–1981: the NHLBI Registry. N Engl J Med 1988;318: ground of the Fluvastatin Angioplasty Restenosis Trial. Br J Clin Pract 265–70. Symp Suppl 1996;77A:40–53. 181. Myler RK, Topol EJ, Shaw RE, et al. Multiple vessel coronary angioplasty: 158. Liu MW, Roubin GS, Robinson KA, et al. Trapidil in preventing restenosis classification, results and patterns of restenosis in 494 consecutive patients. after balloon angioplasty in the atherosclerotic rabbit. Circulation 1990;81: Cathet Cardiovasc Diagn 1987;13:1–15. 1089–93. 182. Holmes DR, Holubkov R, Vlietstra RE, et al, and Co-investigators of the 159. Maresta A, Balducelli M, Cantini L, Casari A, et al, for the STARC NHLBI PTCA Registry. Comparison of complications during percutaneous Investigators. Trapidil (triazolopyrimidine), a platelet-derived growth fac- transluminal coronary angioplasty from 1977 to 1981 and from 1985 to tor antagonist, reduces restenosis after percutaneous transluminal coronary 1986: The NHLBI PTCA Registry. J Am Coll Cardiol 1988;12:1149–55. angioplasty: Results of the randomized double-blind STARC study. Circu- 183. Hartzler GO, Rutherford BD, McConahay DR, Johnson WL, Ligon RW, lation 1994;90:2710–5. Calkins MM. ‘Long-term’ clinical results of multiple lesion coronary 160. Schneider JE, Berk BC, Gravanis MB, et al. Probucol decreases neointimal angioplasty in 500 consecutive patients [abstract]. Circulation 1985;72 Suppl formation in a swine model of coronary artery balloon injury: a possible role III:III-139. for antioxidants in restenosis. Circulation 1993;88:628–37. 184. Cowley MJ, Block PC. A review of the NHLBI PTCA Registry data. In Jang 161. Lee YJ, Daida H, Yokoi H, et al. Effectiveness of probucol in preventing GC, editor. Angioplasty. New York: McGraw-Hill, 1986:368–77. restenosis after percutaneous transluminal coronary angioplasty. Jpn 185. Myler RK, Topol EJ, Shaw RE, et al. Multiple vessel coronary angioplasty: Heart J 1996;37:327–32. classification, results and patterns of restenosis in 494 consecutive patients. 162. Tardif JC, Cote G, Lesperance J, et al. Probucol and multivitamins in the Cathet Cardiovasc Diagn 1987;13:1–15. prevention of restenosis after coronary angioplasty: Multivitamins and 186. Roubin GS, Sutor C, Lembo NJ, et al. Prognosis after multiple vessel Probucol Study Group. N Engl J Med 1997;337:365–72. angioplasty (PTCA) in patients with coronary artery disease [abstract]. 163. Wolinsky H, Thung SW. Use of a perforated balloon catheter to deliver Circulation 1987;76 Suppl IV:IV-465. concentrated heparin into the wall of the normal canine artery. J Am Coll 187. Cowley MG, DiSciascio G, Kelly K, et al. Long-term efficacy of multiple- Cardiol 1991;15:475–81. vessel coronary angioplasty [abstract]. Circulation 1987;76 Suppl IV:IV- 164. Santoian EC, Gravanis MB, Schneider JE, et al. Use of the porous balloon 466. in porcine coronary arteries: rationale for low pressure and volume 188. Dorros G, Lewin RF, Mathiak LM. Percutaneous transluminal coronary delivery. Cathet Cardiovasc Diagn 1993;30:348–54. angioplasty in multivessel coronary disease patients: Short- and long-term 165. Slepian MJ. Polymeric endoluminal paving and sealing: therapeutics at the follow-up in single and multiple dilatations. Clin Cardiol 1988;11:601–12. crossroad of biomechanics and pharmacology. In: Topol EJ, editor. Text- 189. Detre K, Holubkov R, Kelsey S, et al: Percutaneous transluminal coronary book of Interventional Cardiology. Philadelphia: WB Saunders, 1990:647– angioplasty in 1985–1986 and 1977–1981. N Engl J Med 1988;318:265–70. 70. 190. Detre K, Yeh W, Kelsey S, et al. Has improvement in PTCA intervention 166. Nabel EG, Plalutz G, Nabel GJ. Gene transfer into vascular cells. J Am Coll affected long-term prognosis? The NHLBI PTCA Registry experience. Cardiol 1991;17 Suppl B:189B–94B. Circulation 1995;91:2868–75. 167. Condado JA, Waksman R, Gurdiel O, et al. Long-term angiographic and 191. O’Keefe JH Jr, Rutherford BD, McConahay DR, et al. Multivessel clinical outcome after percutaneous transluminal coronary angioplasty and coronary angioplasty from 1980–1989: procedural results and long-term intracoronary radiation therapy in humans. Circulation 1997;96:727–32. outcome. J Am Coll Cardiol 1990;16:1079–102. 168. Teirstein PS, Massullo V, Jani S, et al. Catheter-based radiotherapy to 192. Holmes DR, Berger PB. Complex and multivessel dilatation. In: Topol EJ, inhibit restenosis after coronary stenting. N Engl J Med 1997;336:1697–703. editor. Textbook of Interventional Cardiology. Philadelphia: WB Saunders, 169. Hartzler GO. Percutaneous transluminal coronary angioplasty in multives- 1994:231–50. sel disease. Cathet Cardiovasc Diagn 1983;9:537–41. 193. Mark DB, Nelson CL, Califf RM, et al. Continuing evolution of therapy for 170. Vlietstra RE, Holmes DR Jr, Reeder GS, et al. Balloon angioplasty in coronary artery disease: initial results from the era of coronary angioplasty. multivessel coronary artery disease. Mayo Clin Proc 1983;58:563–7. Circulation 1994;89:2015–25. 171. Dorros G, Stertzer SH, Cowley MJ, Myler RK. Complex coronary angio- 194. Hartz AJ, Kuhn EM, Pryer DB, et al. Mortality after coronary angioplasty plasty: multiple coronary dilatations. Am J Cardiol 1984;53:126C–30C. and coronary artery bypass surgery (the National Medicare Experience). 172. Vandormael MG, Chaitman BR, Ischinger T, et al. Immediate and Am J Cardiol 1992;70:179–85. short-term benefit of multilesion coronary angioplasty: influence of degree 195. Weintraub WS, Jones EL, King SB III, et al. Changing use of coronary of revascularization. J Am Coll Cardiol 1985;6:983–91. angioplasty and coronary bypass surgery in the treatment of chronic 173. Cowley MJ, Vetrovec GW, DiSciascio G, Lewis SA, Hirsh PD, Wolfgang coronary artery disease. Am J Cardiol 1990;65:183–8. TC. Coronary angioplasty of multiple vessels: short-term outcome and 196. O’Keefe JH, Allan JJ, McCallister BD, et al. Angioplasty versus bypass long-term results. Circulation 1985;72:1314–20. surgery for multivessel coronary artery disease with left ventricular ejection 174. Hartzler GO. Percutaneous coronary angioplasty in patients with multives- fraction Յ40 percent. Am J Cardiol 1993;71:897–901. sel disease. In: Jang GC, editor. Angioplasty. New York: McGraw-Hill, 197. Myler RK, Topol EJ, Shaw RE, et al. Multiple vessel coronary angioplasty: 1986:321–36. classification, results and patterns of restenosis in 494 consecutive patients. 175. Myler RK, Topol EJ, Shaw RE, et al. Multiple vessel coronary angioplasty: Cathet Cardiovasc Diagn 1987;13:1–15. classification, results and patterns of restenosis in 494 consecutive patients. 198. Tyras DH, Barner HB, Kaiser GC, et al. Long-term results of myocardial Cathet Cardiovasc Diagn 1987;13:1–15. revascularization. Am J Cardiol 1979;44:1290–6. JACC Vol. 31, No. 4 Suppl B KING 85B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY

199. Cukingnan RA, Carey JS, Wittig JH, Brown BG. Influence of complete 222. CABRI Trial Participants. Coronary Angioplasty vs. Bypass Revasculariza- coronary revascularization on relief of angina. J Thorac Cardiovasc Surg tion Investigation (CABRI) results during the first year. Lancet 1995;346: 1980;79:188–93. 1179–83. 200. Jones EL, Craver JM, Guyton RA, Bone DK, Hatcher CR Jr, Riechwawld 223. RITA Trial Participants. Coronary angioplasty versus coronary artery N. Importance of complete revascularization in performance of the coro- bypass surgery: The Randomised Intervention Treatment of Angina nary bypass operation. Am J Cardiol 1983;51:7–12. (RITA) trial. Lancet 1993;341:573–80. 201. Vandormael M, Deligonul U. Multivessel coronary angioplasty. In: Meier 224. Hamm CW, Reimers J, Ischinger T, et al. A randomized study of coronary B, editor. Interventional Cardiology. Toronto: Hogrefe and Huber, 1989: angioplasty compared with bypass surgery in patients with symptomatic 117–43. multivessel coronary artery disease. N Engl J Med 1994;331:1037–43. 202. Mabin TA, Holmes DR, Smith HC, et al. Follow-up clinical results in 225. Rodriguez A, Boullon F, Perez-Balino N, et al. Argentine randomized trial patients undergoing percutaneous transluminal coronary angioplasty. Cir- of percutaneous transluminal coronary angioplasty versus coronary artery culation 1985;71:754–60. bypass surgery in multivessel disease (ERACI): in-hospital results and 203. Vandormael MG, Chaitman BR, Ischinger T, et al. Immediate and 1-year follow-up. J Am Coll Cardiol 1993;33:1060–7. short-term benefit of multilesion coronary angioplasty: Influence of degree 226. King SB III, Barnhart HX, Kosinski AS, et al. and the EAST Investigators. of revascularization. J Am Coll Cardiol 1985;6:983–91. Angioplasty or surgery for multivessel coronary artery disease: Comparison 204. Bourassa MG, David PR, Costigan T, et al. Completeness of revascular- of eligible registry and randomized patients in the EAST trial and influence ization early after coronary angioplasty (PTCA) in the NHLBI PTCA of treatment selection on outcomes. Am J Cardiol 1997;79:1453–9. Registry [abstract]. J Am Coll Cardiol 1987;Suppl A 9:19A. 227. Veterans Affairs ACME Investigators. Percutaneous transluminal coronary 205. Reeder GS, Holmes DR, Detre K, Costigan T, Kelsey SF. Degree of angioplasty versus medical therapy for stable angina pectoris: outcomes for revascularization in patients with multivessel coronary disease: a report patients with double-vessel versus single-vessel coronary artery disease in a from the National Heart, Lung, and Blood Institute Percutaneous Trans- Veterans Affairs cooperative randomized trial. J Am Coll Cardiol 1997;7: luminal Coronary Angioplasty Registry. Circulation 1988;77:638–44. 1505–11. 206. Thomas ES, Most AS, Williams DO. Coronary angioplasty for patients with 228. RITA-2 Trial Participants. Coronary angioplasty versus medical therapy for multivessel coronary artery disease: follow-up clinical status. Am Heart J angina: The second Randomised Interventional Treatment of Angina 1988;115:8–13. (RITA-2) trial. Lancet 1997;350:461–8. 207. Holmes DR, Vlietstra RE, Hammes LN, Reeder GS, Mock MB. Does the 229. Boden WE, Dai H, on behalf of the VANQWISH Trial Investigators. disadvantage of incomplete revascularization by coronary angioplasty in- Long-term outcomes in non-Q-wave infarction patients randomized to an crease with time? [abstract]. J Am Coll Cardiol 1989;13 Suppl:229A. “invasive” versus “conservative” strategy: results of the multicentre VA 208. Ischinger T, Gruentzig AR, Hollman J, et al. Should coronary arteries with Non-Q-Wave Infarction Strategies In-hospital (VANQWISH) trial [ab- less than 60% diameter stenosis be treated by angioplasty? Circulation stract]. Eur Heart J 1997;18 Suppl:351. 1983;68:148–54. 230. King SB III. Trying to understand BARI. J Am Coll Cardiol 1997;30: 209. Breisblatt WM, Barnes JV, Weiland F, Spaccavento LJ. Incomplete 1426–7. revascularization in multivessel percutaneous transluminal coronary angio- 231. Meyer J, Merx W, Schmitz H, et al. Percutaneous transluminal coronary plasty: the role for stress thallium-201 imaging. J Am Coll Cardiol angioplasty immediately after intracoronary streptolysis of transluminal 1988;11:1183–90. myocardial infarction. Circulation 1982;66:905–13. 210. Bell MR, Bailey KR, Reeder GS, Lapeyre AC III, Holmes DR Jr. 232. Hartzler GO, Rutherford BD, McConahay DR, et al. Percutaneous trans- Percutaneous transluminal angioplasty in patients with multivessel coro- luminal coronary angioplasty with and without thrombolytic therapy for nary disease: how important is complete revascularization for cardiac treatment of acute myocardial infarction. Am Heart J 1983;106:965–73. event-free survival? J Am Coll Cardiol 1990;16:554–62. 233. TIMI Research Group. Immediate vs delayed catheterization and angio- 211. Reeder TS, Holmes DR, Detre K, Costigan T, Kelsey SF. Degree of plasty following thrombolytic therapy for acute myocardial infarction: TIMI revascularization in patients with multivessel coronary disease: a report IIA results. JAMA 1988;260:2849–58. from the National Heart, Lung, and Blood Institute Percutaneous Trans- 234. Simoons ML, Arnold AER, Betriu A, et al. Thrombolysis with tissue luminal Coronary Angioplasty Registry. Circulation 1988;77:638–44. plasminogen activator in acute myocardial infarction: no additional benefit 212. Weintraub WS, King SB III, Jones EL, et al. Coronary surgery and from immediate percutaneous coronary angioplasty. Lancet 1988;1:197– coronary angioplasty in patients with two vessel coronary artery disease. 203. Am J Cardiol 1993;71:511–7. 235. Topol EJ, Califf RM, George BS, et al. A randomized trial of immediate 213. King SB III, Lembo NJ, Weintraub WS, et al. A randomized trial versus delayed elective angioplasty after intravenous tissue plasminogen comparing coronary angioplasty with coronary bypass surgery. N Engl activator in acute myocardial infarction. N Engl J Med 1987;317:581–8. J Med 1994;331:1044–50. 236. TIMI Study Group. Comparison of invasive and conservative strategies 214. Zhao X-Q, Brown BG, Stewart DK, et al. Effectiveness of revascularization after treatment with intravenous tissue plasminogen activator in acute in the Emory Angioplasty versus Surgery Trial: a randomized comparison myocardial infarction: results of the Thrombolysis in Myocardial Infarction of coronary angioplasty with bypass surgery. Circulation 1996;93:1954–62. (TIMI) phase II trial. N Engl J Med 1989;320:618–27. 215. Mark DB, Nelson CL, Califf RM, et al. Continuing evolution of therapy for 237. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study coronary artery disease: Initial results from the era of coronary angioplasty. Group. SWIFT trial of delayed elective intervention vs conservative treat- Circulation 1994;89:2015–25. ment after thrombolysis with antistreplase in acute myocardial infarction. 216. Holmes DR Jr, Vlietstra RE. Balloon angioplasty in acute and chronic BMJ 1991;302:555–60. coronary artery disease. JAMA 1989;261:2109–15. 238. ISAM Study Group. A prospective trial of Intravenous Streptokinase in 217. Weintraub WS, Jones EL, King SB III, et al. Changing use of coronary Acute Myocardial Infarction (ISAM): mortality, morbidity and infarct size angioplasty and coronary bypass surgery in the treatment of chronic at 21 days. N Engl J Med 1986;314:1465–71. coronary artery disease. Am J Cardiol 1990;65:183–8. 239. Gruppo Italiano per lo Studio della Streptochinasi nell’Inarto Miocardico 218. O’Keefe JH, Allan JJ, McCallister BD, et al. Angioplasty versus bypass (GISSI). Effectiveness of intravenous thrombolytic treatment in acute surgery for multivessel coronary artery disease with left ventricular ejection myocardial infarction. Lancet 1986;1:397–401. fraction Յ40 percent. Am J Cardiol 1993;71:897–901. 240. ISIS-2 (Second International Study of Infarct Survival) Collaborative 219. Pocock SJ, Henderson RA, Rickards AF, et al. Meta-analysis of random- Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or ised trials comparing coronary angioplasty with bypass surgery. Lancet neither among 17,187 cases of suspected acute myocardial infarction: 1995;3435:1184–9. ISIS-2. Lancet 1988;2:349–60. 220. King SB III, Lembo NJ, Weintraub WS, Kosinski AS, Barnhart HX, Kutner 241. Califf RM, Topol EJ, Stack RS, et al. Evaluation of combination thrombo- MH. Emory Angioplasty vs. Surgery Trial (EAST): design, recruitment and lytic therapy and timing of cardiac catheterization in acute myocardial baseline description of patients. Am J Cardiol 1995;75:42C–59C. infarction: results of Thrombolysis and Angioplasty in Myocardial Infarc- 221. The Bypass Angioplasty Revascularization Investigation (BARI) Investiga- tion–phase 5 randomized trial. Circulation 1991;83:1543–56. tors. Comparison of coronary bypass surgery with angioplasty in patients 242. Thrombolysis in Myocardial Infarction Investigators. Value of rescue with multivessel disease. N Engl J Med 1996;335:217–25. percutaneous transluminal coronary angioplasty following unsuccessful 86B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B

thrombolytic therapy in patients with acute myocardial infarction. Am J 263. Safian RD, Grines CL, May MA, et al. Clinical and angiographic results of Cardiol 1995;76:1108–11. transluminal extraction coronary atherectomy in saphenous vein bypass 243. Ellis SG, da Silva ER, Heyndrickx G, et al. Randomized comparison of grafts. Circulation 1994;89:302–12. rescue angioplasty with conservative management of patients with early 264. Safian RD, May MA, Lichtenberg A, et al. Detailed clinical and angio- failure thrombolysis for acute anterior myocardial infarction. Circulation graphic analysis of transluminal extraction coronary atherectomy for com- 1994;90:2280–4. plex lesions in native coronary arteries. J Am Coll Cardiol 1995;25:848–54. 244. Grines CL, Browne KF, Marco J, et al. A comparison of immediate 265. Kaplan BM, Larkin T, Safian RD, et al. Prospective study of extraction angioplasty with thrombolytic therapy for acute myocardial infarction. atherectomy in patients with acute myocardial infarction. Am J Cardiol N Engl J Med 1993;328:673–9. 1996;78:383–8. 245. Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, 266. Ritchie J, Hansen D, Vracko R, Auth D. Mechanical thrombolysis: a new Gersh BJ, for the Mayo Coronary Care Unit and Catheterization Labora- rotational catheter approach for acute thrombi. Circulation 1986;73:1006– tory Groups. Immediate angioplasty compared with the administration of a 12. thrombolytic agent followed by conservative treatment for myocardial 267. Hansen D, Auth D, Vracko R, Ritchie J. Mechanical thrombectomy: a infarction. N Engl J Med 1993;328:685–91. comparison of two rotational devices and balloon angioplasty in subacute 246. Zijlstra F, de Boer MJ, Hoomtje JCA, Reiffers S, Reiber JHC, Surya- canine femoral thrombosis. Am Heart J 1987;114:1223–31. pranata H. A comparison of immediate coronary angioplasty with intrave- 268. Fourrier J, Bertrand M, Auth D, Lablanche J, Gommeaux A, Brunetaud J. nous streptokinase in acute myocardial infarction. N Engl J Med 1993;328: Percutaneous coronary rotational angioplasty in humans: preliminary re- 680–4. port. J Am Coll Cardiol 1989;14:1278–82. 247. Angioplasty Substudy Investigators. A clinical trial comparing primary 269. Reifart N, Vandormael M, Krajcar M, et al. Randomized comparison of coronary angioplasty with tissue plasminogen activator for acute myocardial angioplasty of complex coronary lesions at a single center: Excimer Laser, infarction: the Global Use of Strategies to Open Occluded Coronary Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) Arteries in Acute Coronary Syndromes (GUSTO IIb). N Engl J Med study. Circulation 1997;96:91–8. 1997;336:1621–8. 270. Teirstein PS, Warth DC, Haq N, et al. High speed rotational coronary 248. Laster SB, Rutherford BD, McConahay DR, et al. Directional atherectomy atherectomy for patients with diffuse coronary artery disease. J Am Coll of the left main coronary artery: acute and long term results [abstract]. Cardiol 1991;18:1694–701. J Am Coll Cardiol 1994;25 Suppl A:386A. 271. Ellis SG, Popma JJ, Buchbinder M, et al. Relation of clinical presentation, 249. Lewis BE, Leya FS, Johnson SA, Grassman ED, McKleman TL, Hwang M. stenosis morphology and operator technique to the procedural results of Outcomes of angioplasty (PTCA) and atherectomy (DCA) for bifurcation rotational atherectomy and rotational atherectomy facilitated angioplasty. and nonbifurcation lesions in CAVEAT [abstract]. Circulation 1993;88 Circulation 1994;89:882–92. Suppl I:I-601. 272. Litvack F, Grundfest W, Goldenberg T, Laudenslager J, Forrester J. 250. Leya FS, Lewis BE, Sumida CW, et al. Modified “kissing” atherectomy Percutaneous excimer laser angioplasty of aortocoronary saphenous vein procedure with dependable protection of side branches by two-wire tech- grafts. J Am Coll Cardiol 1989;14:803–8. nique. Cathet Cardiovasc Diagn 1992;27:155–61. 273. Litvack F, Eigler N, Margolis J, et al. Percutaneous excimer laser coronary 251. Tuzcu EM, Berkalp B, DeFranco AC, et al. The dilemma of diagnosing angioplasty. Am J Cardiol 1990;66:1027–32. coronary calcification: angiography versus intravascular ultrasound. J Am 274. Murphy-Chutorian D, Kosek J, Mok W, et al. Selective absorption of Coll Cardiol 1996;27:832–8. ultraviolet laser energy by human atherosclerotic plaque treated with 252. Topol EJ, Leya F, Pinkerton CA, et al. A comparison of directional tetracycline. Am J Cardiol 1985;55:1293–7. coronary atherectomy with coronary angioplasty in patients with coronary 275. Vandormael M, Reifart N, Preusler W, et al. In hospital costs comparison artery disease. N Engl J Med 1993;329:221–7. of excimer laser angioplasty, rotational atherectomy (Rotablator) and 253. Holmes DR Jr, Topol EJ, Califf RM, et al. A multicenter, randomized trial balloon angioplasty for complex coronary lesions: A randomized trial of coronary angioplasty versus directional atherectomy for patients with (ERBAC) [abstract]. J Am Coll Cardiol 1994;25 Suppl A:753A–4A. saphenous vein bypass graft lesions. Circulation. In press. 276. Douglas JS Jr, Ghazzal ZMG, Ba’albaki HA, Miller SJ, King SB III. 254. Adelman AG, Cohen EA, Kimball BP, et al. A comparison of directional Excimer laser coronary angioplasty of ostial lesions: Acute success and atherectomy with balloon angioplasty for lesions of the left anterior complications [abstract]. Cathet Cardiovasc Diagn 1991;23:75. descending coronary artery. N Engl J Med 1993;329:228–33. 277. Eigler NL, Douglas JS Jr, Margolis JR, Hestrin L, Litvack FL, ELCA 255. Elliott JM, Berdan LG, Holmes DR, One-year follow-up in the Coronary Investigators: Excimer laser coronary angioplasty of aorto-ostial stenosis: Angioplasty Versus Excisional Atherectomy Trial (CAVEAT I). Circula- results of the ELCA Registry. Circulation 1993;88:2049–57. tion 1995;91:2158–66. 278. Bittl JA, Sanborn TA, Yardley DE, et al. Predictors of outcome of 256. Baim DS, Kuntz RE, Sharma SK, et al. Acute results of the randomized percutaneous excimer laser coronary angioplasty of saphenous vein bypass trial of the Balloon versus Optimal Atherectomy Trial (BOAT). Circulation graft lesions. The percutaneous Excimer Laser Coronary Angioplasty 1995;91:1966–74. Registry. Am J Cardiol 1994;74:144–8. 257. Boehrer JD, Ellis SG, Keeler GP, et al. Differential benefit of directional 279. de Marchene EJ, Mallon SM, Knopf WD, et al. Effectiveness of homium atherectomy over angioplasty for left anterior descending in proximal, non laser-assisted coronary angioplasty. Am J Cardiol 1994;73:117–21. ostial lesions: Results from CAVEAT [abstract]. J Am Coll Cardiol 1994;25 280. Litvack F, Eigler N, Margolis J, et al. Percutaneous excimer laser coronary Suppl A:386A. angioplasty: Results in the first consecutive 3,000 patients. J Am Coll 258. Popma JJ, Baim DS, Kuntz RE, et al. Early and late quantitative angio- Cardiol 1994;23:323–9. graphic outcome from Optimal Atherectomy Restenosis Study (OARS) 281. Ghazzal Z, Hearn J, Litvack F, et al. Morphologic predictors of acute [abstract]. J Am Coll Cardiol 1996;27 Suppl A:291A. complications after percutaneous excimer laser coronary angioplasty: re- 259. Holmes DR Jr, Topol EJ, Califf RM, et al. A multicenter, randomized trial sults of a comprehensive angiographic analysis: Importance of the eccen- of coronary angioplasty versus directional atherectomy for patients with tricity index. Circulation 1992;86:820–7. saphenous vein bypass graft lesions: CAVEAT-II Investigators. Circulation 282. Karsch K, Haase K, Voelker W, Baumbach A, Mauser M, Seipel L. 1995;91:1966–74. Percutaneous coronary excimer laser angioplasty in patients with stable and 260. Popma JJ, Leon MB, Mintz GS, et al. Results of coronary angioplasty using unstable angina pectoris: acute results and incidence of restenosis during the transluminal extraction catheter. Am J Cardiol 1992;70:1526–32. 6-month follow-up. Circulation 1990;81:1849–59. 261. Baim DS, Kent KM, King SB III, et al. Evaluating new devices: acute (in 283. Appelman YE, Piek JJ, deFeyter PJ, Koolen JJ, Strikwerda S, Margolis JR. hospital) results from the New Approaches to Coronary Intervention Excimer laser coronary angioplasty versus balloon angioplasty used in Registry. Circulation 1994;89:471–81. long-term lesions: The long-term results of the AMRO Trial [abstract]. 262. Moses JW, Teirstein PS, Sketch MH Jr, et al. Angiographic determinants of J Am Coll Cardiol 1995;25 Suppl A:329A. risk and outcome of coronary embolus and myocardial infarction (MI) with 284. Appelman JY, Koolen JJ, deFeyter PJ, Strikwerda S, David GK, Redekop the transluminal extraction catheter (TEC): a report from the New K. Long-term outcome of excimer laser angioplasty versus balloon angio- Approaches to Coronary Intervention (NACI) Registry. [abstract] J Am plasty in functional and total coronary occlusions [abstract]. J Am Coll Coll Cardiol 1994;25 Suppl A:220A. Cardiol 1995;25 Suppl A:330A. JACC Vol. 31, No. 4 Suppl B KING 87B March 15, 1998:64B–88B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY

285. Vandormael M, Riefart N, Preusler W. Six month follow-up results 306. King SB III, Williams DO, Chougule P, et al. Endovascular beta radiation following excimer laser angioplasty, rotational atherectomy and balloon to reduce restenosis after coronary balloon angioplasty: results of the beta angioplasty for complex lesions: ERBAC Study [abstract]. Circulation energy restenosis trial (BERT). Circulation. In press. 1994;90 Suppl I:I-213. 307. Waksman R, Robinson KA, Crocker IR, Gravanis MB, Cipolla GD, King 286. Ghazzal ZM, Burton E, Weintraub WS, et al. Predictors of restenosis after SB III. Endovascular low-dose irradiation inhibits neointima formation excimer laser coronary angioplasty. Am J Cardiol 1995;75:1012–4. after coronary artery balloon injury in swine: a possible role for radiation 287. Serruys PW, Hamburger J, Fleck E, Koolen JJ, Teunissen. Laser guide therapy in restenosis prevention. Circulation 1995;91:1533–9. wire: A powerful tool in recanalization of chronic total coronary occlusion 308. Waksman R, Robinson KA, Crocker IR, et al. Intracoronary radiation [abstract]. Circulation 1995;92 Suppl I:I-76. before stent implantation inhibits neointima formation in stented porcine 288. King SB III, Yeh W, Holubkov R, et al, for the Investigators of the NHLBI coronary arteries. Circulation 1995;92:1383–6. PTCA and NACI Registries. Balloon angioplasty versus new device inter- 309. Stone GW, Hodgson JM, Goar FG, et al. Improved procedural results of vention, clinical outcomes: a comparison of the NHLBI PTCA registry and coronary angioplasty with intravascular ultrasound-guided balloon sizing: the NACI registry. J Am Coll Cardiol. In press. the CLOUT pilot trial. Circulation 1997;95:2044–52. 289. Roubin GS, King SB III, Douglas JS Jr, Lembo NJ, Robinson KA. 310. McPherson DD, Kane BJ. Intravascular ultrasound: three-dimensional Intracoronary stenting during percutaneous transluminal coronary angio- applications and forward viewing. Cardiol Clin 1997;15:63–75. plasty [abstract]. Circulation 1990;81 Suppl IV:IV-92–100. 311. Gorge G, Ge J, Haude M, et al. Intravascular ultrasound for evaluation of 290. Hearn JA, King SB III, Douglas JS Jr, Carlin SF, Lembo NJ, Ghazzal ZMB. coronary arteries. Herz 1996;21:78–89. Clinical and angiographic outcomes after coronary artery stenting for acute 312. Bach RG, Donohue TJ, Kern MJ. Intracoronary Doppler flow velocity or threatened closure after percutaneous transluminal coronary angio- measurements for the evaluation and treatment of coronary artery disease. plasty: initial results with a balloon-expandable, stainless steel design. Curr Opin Cardiol 1995;10:434–42. Circulation 1993;88:2086–96. 313. Kern MJ, Donohue TJ, Aguirre FV, et al. Assessment of angographically 291. Dean LS, George CJ, Roubin GS, et al. Bailout and corrective use of intermediate coronary artery stenosis using the Doppler FloWire. Am J Gianturco-Roubin flex stents after percutaneous transluminal coronary angioplasty: operator reports and angiographic core laboratory verification Cardiol 1993;71:26D–33D. from the National Heart, Lung, and Blood Institute/New Approaches to 314. Anderson HV, Roubin GS, Leimgruber PP, et al. Transtenotic pressure Coronary Intervention Registry. J Am Coll Cardiol 1997;5:934–40. gradient measurements during percutaneous transluminal coronary angio- 292. Schatz R, Baim D, Leon M, et al. Clinical experience with the Palmaz- plasty. Circulation 1986;73:1223–30. Schatz coronary stent: initial results of a multicenter study. Circulation 315. Redd D, Roubin GS, Leimgruber PP, Abi-Mansour P, Douglas JS, King 1991;83:148–61. SB. The transstenotic pressure gradient trend as a predictor of acute 293. Wong SC, Baim DS, Schatz RA, et al. Immediate results and late outcomes complications after percutaneous transluminal coronary angioplasty. Cir- after stent implantation in saphenous vein graft lesions: the multicenter US culation 1987;76:792–801. Palmaz-Schatz stent experience: The Palmaz-Schatz Stent Study Group. 316. Pijls NHJ, Van Son JAM, Kirkeeide RL, De Bruyne B, Gould KL. J Am Coll Cardiol 1995;26:704–12. Experimental basis of determining maximum coronary myocardial, and 294. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of collateral blood flow by pressure measurements for assessing functional coronary stent placement and balloon angioplasty in the treatment of stenosis severity before and after PTCA. Circulation 1993;87:1354–67. coronary artery disease. N Engl J Med 1994;331:496–501. 317. The EPIC Investigators. Use of a monoclonal antibody directed against the 295. Serruys PW, de Jaegere P, Kiemeneij F, et al, on behalf of the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. BENESTENT Study Group: a comparison of balloon-expandable stent N Engl J Med 1994;330:956–61. implantation with balloon angioplasty in patients with coronary artery 318. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor block- disease. N Engl J Med 1994;331:489–95. ade and low-dose heparin during percutaneous coronary revascularizatiaon. 296. Barragan P, Sainsous J, Silvestri M, et al. Ticlopidine and subcutaneous N Engl J Med 1997;336:1689–96. heparin as an alternative regimen following coronary stenting. Cathet 319. The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa Cardiovasc Diagn 1994;32:133–8. blockade with tirofiban on adverse cardiac events in patients with unstable 297. Colombo A, Hall P, Nakamura S, et al. Intracoronary stenting without angina or acute myocardial infarction undergoing coronary angioplasty. anticoagulation accomplished with intravascular ultrasound guidance. Cir- Circulation 1997;96:1445–53. culation 1995;91:1676–88. 320. Harrington RA. Design and methodology of the PURSUIT trial: evaluating 298. Schoemig A Newmann FJ, Kastrati A, et al. A randomized comparison of entifibatide for acute ischemic coronary syndromes (Platelet Glycoprotein antiplatelet and anticoagulant therapy after the placement of coronary IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Ther- artery stents. N Engl J Med 1996;334:1084–9. apy trial). Am J Cardiol 1997;80:34B–38B. 299. Schuhlen H, Hadamitzky M, Walter H, Ulm K, Schomig A. Major benefit 321. Grines CL, Schreiber TL, Savas V, et al. A randomized trial of low osmolar from antiplatelet therapy for patients at high risk for adverse cardiac events ionic versus nonionic contrast media in patients with myocardial infarction after coronary Palmaz-Schatz stent placement: analysis of a prospective risk or unstable angina undergoing percutaneous transluminal coronary angio- stratification protocol in the Intracoronary Stenting and Antithrombotic plasty. J Am Coll Cardiol 1996;27:1381–6. Regimen (ISAR) Trial. Circulation 1997;95:2015–21. 322. Ritchie JL, Nissen SE, Douglas JS Jr, et al. Use of nonionic or low osmolar 300. Leon MB, Cutlip DE, Fitzpatrick M, et al. Acute results and one-year contrast agents in cardiovascular procedures. J Am Coll Cardiol 1993;21: outcomes of the Stent Anti-thrombotic Regimen Study (STARS) registry 269–73. [abstract]. Circulation 1997;96 Suppl I:I-594. 323. Lembo NJ, King SB III, Roubin GS, Black AJ, Douglas JS Jr. Effects of 301. Savage MP, Douglas JS Jr, Fischman DL, et al, for the Saphenous Vein De nonionic contrast media on complications of percutaneous transluminal Novo Trial Investigators. Stent placement compared with balloon angio- coronary angioplasty. Am J Cardiol 1991;67:1046–50. plasty for obstructed coronary bypass grafts. N Engl J Med 1997;337:740–7. 302. Mehran R, Mintz GS, Popma JJ, et al. Mechanisms and results of balloon 324. Poole JCF, Cromwell SB, Benditt EP. Behavior of smooth muscle cells and angioplasty for the treatment of in-stent restenosis. Am J Cardiol 1996;78: formation of extracellular structures in the reaction of arterial walls to 618–22. injury. Am J Pathol 1971;62:391–404. 303. Dussaillant GR, Mintz GS, Pichard AD, et al. Small stent size and intimal 325. Jorgensen L, Roswell HC, Hovig T, Mustard JF. Resolution and organiza- hyperplasia contribute to restenosis: a volumetric intravascular ultrasound tion of platelet-rich mural thrombi in carotid arteries of swine. Am J Pathol analysis. J Am Coll Cardiol 1995;26:720–4. 1967;51:681–719. 304. Hong MK, Kent KM, Mehran R, et al. Continuous subcutaneous angio- 326. Webster WS, Bishop SP, Geer JC. Experimental aortic intimal thickening: peptin treatment significantly reduces neointimal hyperplasia in a porcine I: Morphology and source of intimal cells. Am J Pathol 1974;76:245–64. coronary in-stent restenosis model. Circulation 1997;95:449–54. 327. Schlichter JG. Experimental medionecrosis of the aorta. Arch Pathol 305. Reimers B, Moussa I, Akiyama T, et al. Long-term clinical follow-up after 1946;42:182–92. successful repeat percutaneous intervention for stent restenosis. J Am Coll 328. Buck RC. Intimal thickening after ligature of arteries: an electron micro- Cardiol 1997;30:86–92. scopic study. Circ Res 1961;9:418–26. 88B KING JACC Vol. 31, No. 4 Suppl B DEVELOPMENT OF INTERVENTIONAL CARDIOLOGY March 15, 1998:64B–88B

329. Stemerman MB, Spaet TH, Pitlick F, Cintron J, Lejnieks I, Tiell ML. D, editors. Strategic Approaches in Coronary Intervention. Baltimore: Intimal healing: the pattern of reendothelialization and intimal thickening. Williams & Wilkins, 1996:698–710. Am J Pathol 1977;87:125–42. 345. Edelman ER, Levy RJ, editors. Molecular Interventions and Local Drug 330. Groves HM, Kinlough-Rathbone RL, Richardson M, Jorgensen L, Moore Delivery, Frontiers in Cardiology Series. Cambridge (MA): Cambridge S, Mustard JF. Thrombin generation and fibrin formation following injury University Press, 1995. to rabbit neointima: Studies of vessel wall reactivity and platelet survival. 346. Waksman R, King SB III, Crocker IR, Mould RF, editors. Vascular Lab Invest 1982;46:605–12. Brachytherapy. Veneendal, The Netherlands: Nucletron-Oldeft, 1996. 331. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after 347. March K, editor. Gene Transfer in the Cardiovascular System: Experimen- arterial injury: I: smooth muscle cell growth in the absence of endothelium. tal Approaches and Therapeutic Implications. Boston: Kluwer, 1997. Lab Invest 1983;49:327–43. 348. Nunes GL, Sgoutas DS, Redden RA, et al. Combination of vitamins C and 332. Ross R, Glomset JA. The pathogenesis of atherosclerosis. N Engl J Med E alters the response to coronary balloon injury in the pig. Arterioscler 1976;295:369–73. Thromb Vasc Biol 1995;15:156–65. 333. Nikol S, Huehns TY, Hofling B. Molecular biology and post-angioplasty 349. Wu K, Robinson KA, Cui J, et al. Chronic treatment with a glutathione restenosis. Atherosclerosis 1996;123:17–31. peroxidase mimic, BXT-51072, improves in vitro relaxation to ACh in pig 334. Wilcox JN. Molecular biology: Insight into the causes and prevention of coronary arteries with regenerated endothelium [abstract]. Circulation restenosis after arterial intervention. Am J Cardiol 1993;72:88E–95E. 1996;94 Suppl I:I-522. 335. Libby P, Schwartz D, Brogi E, Tanaka H, Clinton SK. A cascade model for 350. Nunes GL, Robinson KA, Kalynych A, King SB III, Sgoutas DS, Berk BC. restenosis: A special case of atherosclerosis progression [abstract]. Circu- Vitamins C and E inhibit O2 production in the pig coronary artery. lation 1992;86 Suppl III:III-47–52. Circulation 1997;96:3593–601. 336. Lee PC, Gibbons GH, Dzau VJ. Cellular and molecular mechanisms of 351. Yokoi H, Daida H, Kuwbara Y, et al. Effectiveness of an antioxidant in coronary artery restenosis. Coron Artery Dis 1993;4:254–9. preventing restenosis after percutaneous transluminal coronary angio- 337. Badimon L, Alfon J, Royo T, Berrozpe M, et al. Cell biology of restenosis plasty: the Probucol Angioplasty Restenosis Trial. J Am Coll Cardiol post-angioplasty. Z Cardiol 1995;84 Suppl 4:145–9. 1997;30:855–62. 338. Panda D, Kundu GC, Lee BI, et al. Potential roles of osteopontin and 352. Ryan TJ, Bauman WB, Kennedy JW, et al. ACC/AHA Task Force Report: ␣ ␤ V 3 integrin in the development of coronary artery restenosis after guidelines for percutaneous transluminal coronary angioplasty. J Am Coll angioplasty. Proc Natl Acad Sci USA 1997;94:9308–13. Cardiol 1993;22:2033–54. 339. van Bockxmeer FM, Mamotte CD, Gibbons FA, Burke V, Taylor RR. 353. Hannan EL, Racz M, Ryan TJ, et al. Coronary angioplasty volume- Angiotensin-converting enzyme and apolipoprotein E genotypes and re- outcome relationships for hospitals and cardiologists. JAMA 1997;277: stenosis after coronary angioplasty. Circulation 1995;92:2066–71. 892–8. 340. Johansson SR, Nilsson J, Hamsten A, Emanuelsson H. Mitogenic activity in 354. Jollis JG, Peterson ED, Nelson CL, et al. Relationship between physician connection with coronary angioplasty. Eur Heart J 1993;14:904–9. and hospital coronary angioplasty volume and outcome in elderly patients. 341. Speir E, Modali R, Huang ES, et al. Potential role of human cytomegalo- Circulation 1997;95:2485–91. virus and p53 interaction in coronary restenosis. Science 1994;265:391–4. 355. Ellis SG, Weintraub W, Holmes D, Shaw R, Block PC, King SB III. 342. O’Brien ER, Garvin MR, Stewart DK, et al. Osteopontin is synthesized by Relation of operator volume and experience to procedural outcome of macrophage, smooth muscle, and endothelial cells in primary and rest- percutaneous coronary revascularization at hospitals with high interven- enotic human coronary atherosclerotic plaques. Arterioscler Thromb 1994; tional volumes. Circulation 1997;96:2479–84. 14:1648–56. 356. Topol EJ, Califf RM, Van de Werf F, et al, for the Virtual Coordinating 343. Kearney M, Pieczek A, Haley L, et al. Histopathology of in-stent restenosis Center for Global Collaborative Cardiovascular Research (VIGOUR) in patients with peripheral artery disease. Circulation 1997;95:1998–2002. Group. Perspectives on large-scale cardiovascular clinical trials for the new 344. Robinson KA, King SB III. Prospects for local delivery. In Ellis S, Holmes millennium. Circulation 1997;95:1072–82.