Subject Review. Advances in Interventional Cardiology

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1 Subject Review Advances in Interventional Cardiology DAVID R. HOLMES, Jr., M.D., RONALD E. VLIETSTRA, M.B.,Ch.B.,* STEVEN J. REITER, M.D.,t DENNIS R. BRESNAHAN, M.D.,i Division of Cardiovascular Diseases and Internal Medicine The field of interventional cardiology is growing widely. This growth is the result of improvements in existing technology, development of new technology, and expansion of criteria for the selection of patients. Percutaneous transluminal coronary angioplasty (PTCA) remains the mainstay and is used to treat an increasing number of patients with coronary artery disease that manifests as stable or unstable angina or acute myocardial infarction. Atherectomy is being used to "debulk" lesions and remove atheromatous plaque as well as to remove intimal flaps after PTCA. The insertion of an intracoronary stent is a strategy designed to treat intimal dissections and acute closure as well as to attempt to decrease the incidence of restenosis. Finally, intracoronary laser therapy independently or in combination with PTCA is being evaluated as a treatment approach for more diffuse disease, acute occlusion, and prevention of restenosis. The year 1977 ushered in a new era in the treatment of patients with cardiovascular disease interventional cardiology.' With the introduction of percutaneous transluminal coronary angioplasty (PTCA) in that year, the mindset that the ostia of the coronary arteries were inviolate was broken. Since then, an explosive growth in technology has facilitated the development and testing of additional procedures such as coronary atherectomy, arterial stents, and intra-arterial laser therapy. This growth is expected to continue and should provide an expanding number of treatment options in ad- *CuiTent address: Watson Clinic, Lakeland, Florida. tcurrent address: Oklahoma Heart Institute, Tulsa, Oklahoma. ^Current address: Cardiovascular Consultants, Kansas City, Missouri. Address reprint requests to Dr. D. R. Holmes, Jr., Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN Mayo Clin Proc 65: , dition to conventional medical and surgical therapy. PTCA PTCA was initially reserved for patients with single-vessel disease who had a single, concentric subtotal stenosis, well-preserved left ventricular function, and stable but medically refractory angina.' * Although these patients still remain ideal candidates for PTCA, they account for only a minority of those who currently undergo dilation. An estimated 150,000 dilations were performed in 1986, and rapid growth continues. This exponential growth is the result of changing criteria for selection of patients, improved technology that facilitates dilation of more severe and complex coronary artery disease, and the number of patients who have restenosis and require repeat dilation.^'^' Technologic Considerations. Achieving optimal results with dilation is dependent on four factors: (1) adequate catheterization facili-

2 566 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 ties, (2) up-to-date angioplasty equipment, (3) appropriate selection of patients, and (4) operator experience. Each of these four factors is important in achieving the desired result. The catheterization laboratory has become increasingly specialized.'"'" For interventional procedures, the requirements for optimal imaging have become more stringent. The imaging equipment must obtain and display high-quality images to allow visualization of multiple views of the coronary arteries before, during, and after dilation. Without the capability of high-quality stop-action video recording, dilation should not be performed. Radiation exposure to patients, physicians, and technical staff has become an increasingly important concern."'^ During dilation, fluoroscopy times are increased; this increase is proportional to the number of vessels being dilated. As more multivessel dilation procedures are performed, this problem will be magnified. Careful shielding ofthe equipment and radiation aprons for physicians and technical personnel can limit exposure. Recently, new digital imaging techniques have shown considerable promise in actually reducing radiation exposure in addition to improving the quality of the images."'" Major changes in the technology of balloon dilation equipment have occurred since its introduction in ,7,14-19 x^ese changes, which make the initial equipment seem crude, inflexible, and cumbersome, have facilitated the expanded use of dilation and the improvement in success rates from approximately 60% in 1977 to 90% in Technologic advances continue; during 1988, approximately 20 new catheter systems were introduced. Knowledge of the advantages and disadvantages of these systems is essential for optimizing dilation. In some circumstances, a variety of dilation catheters will be equally effective; in other circumstances, the specific characteristics of a single dilating catheter may be necessary for a successful dilation procedure. Dilation systems consist of three components: a guiding catheter needed for intubation of the ostium of the vessel to be dilated; the balloon dilating catheter itself; and a guide wire that is removable, movable, or fixed to traverse the stenosis. Guiding Catheters. ^A large variety of currently available guiding catheters facilitate dilation from either a brachial or a femoral approach. The initial catheters used were 9 F in diameter to accommodate the large dilating catheters. Since then, smaller guiding catheters, usually 8 F but even 7 F in some instances, have become widely used. Even though these catheters have become smaller in external diameter, the internal diameter has increased in size, a feature that allows excellent opacification of the coronary artery with test injections during dilation. Some of these catheters have a deformable soft tip,' which is intended to help decrease trauma to the coronary ostia during dilation. Dilating Catheters. ^The available dilating catheters have changed substantially. The sizes range from 1.5 to 4.0 mm for coronary arterial and vein graft dilations. Changes in the design of these catheters have provided a lower profile so that they can more easily pass through stenoses, better "trackability" so that they can be used in tortuous vessels, and also some stiffness of the catheter shaft so that the catheter can be "pushed" across the stenoses. At the same time, the balloon material has become stronger. Made of polyvinyl chloride or polyethylene, these balloons can routinely deliver 10 to 12 atmospheres or now even up to 20 atmospheres. Although most of these balloons maintain a constant diameter over a wide range of pressures, some will expand slightly (approximately 10%) above 8 atmospheres. The specific balloon dilation catheter chosen depends on the preference of the physician, the size of the artery to be dilated, its location within the coronary arterial tree, and the severity of the stenosis. Guide Wires. The third essential component of dilation systems is the guide wire. The earliest systems had a fixed guide wire at the tip of the dilating catheter which lacked directional control. This construction limited the ability to negotiate through the coronary arterial system to reach the stenosis. A major design modification was the subsequent introduction of a mov-

3 Mayo Clin Proc, April 1990, Vol 65 INTERVENTIONAL CARDIOLOGY 567 able guide wire that could be shaped, independently directionally controlled, and removed. Guide wires are now available in sizes from 0.36 to 0.46 mm and with varied flexibility and stiffness. Even smaller wires (0.25 or 0.30 mm) are planned for the future. Most guide wire systems allow extension and exchange capability so that the wire can be placed across the stenosis and a variety of dilating catheters can be used, if needed, for dilation. Some of these movable guide wire systems have been modified so that the guide wire can be advanced within the coronary artery but not totally withdrawn from it through the balloon catheter. This design allows excellent trackability within the coronary artery but prevents the use of a long exchange wire. A recent catheter design has returned to a fixed guide wire system.'^'^ This system is essentially a balloon on a thin guide wire and has the advantage of the lowest profile; thus, the ability to cross very severe stenoses is improved. Although not as "steerable" as movable core systems, these new devices still are extremely helpful. Selection of the balloon and guide wire combination depends also on the preference of the physician and the detailed anatomy of the patient. For competent performance of PTCA, appropriate training and sufficient ongoing experience are needed.^** Not all angiographers should expect to perform angioplasty; difficult multivessel cases should be directed to the most experienced practitioners. Procedural Details. ^A percutaneous femoral arterial approach is most commonly used for PTCA although catheters for a brachial cutdown method are available. Usually, an 8-F sheath is placed in the femoral artery after local infiltration with lidocaine. This sheath allows easy access during and immediately after the procedure. Both long (23-cm) and short (10-cm) sheaths are available. If the iliac vessels are severely tortuous, the long sheath may facilitate guiding manipulation of the catheter. After successful dilation, the sheath is sutured in place and left for a variable period. This sheath allows easy arterial access after PTCA if a complication occurs that demands urgent angiography. The time that the sheath is left in place depends on local practice and details of the outcome of dilation. If, for example, after PTCA a major dissection or a large amount of thrombus is present, the sheath may be left in for 24 hours and then repeat angiography can be performed. The most common practice is to leave the sheath in place from 6 to 24 hours and then remove it. In uncomplicated dilation cases, the 6-hour duration is more widely used. After removal of the sheath, local compression is used to obtain hemostasis. Subsequently, a period of 6 to 8 hours of bed rest is routine, after which ambulation is allowed. The patient can usually be dismissed from the hospital the day after removal of the sheath. If the sheath is removed the afternoon of dilation, the patient may be dismissed the next day. Adjunctive Therapy. Before dilation, antiplatelet agents, including aspirin alone or aspirin in combination with dipyridamole, are given. This therapy has been shown to decrease the incidence of thromboembolic complications associated with dilation.^' Heparin is usually administered as a bolus of 10,000 to 15,000 U after arterial entry and supplemented on the basis of activated clotting time measurements.^^ If the sheath is to be left in more than 4 to 6 hours, a heparin infusion at 1,000 U/h is used. If the sheath is to be removed 4 to 6 hours after the end of the procedure, no additional heparin is given. Requirements for heparin vary depending on, among other factors, the size of the patient and the duration of the procedure. The activated clotting time has been found to be valuable in assessing the level of anticoagulant effect during the procedure and before removal of the sheath.^^ If the procedure is lengthy, additional heparin should be given. Sublingually administered nitrates are usually given before dilation and may be continued for 24 hours to alleviate any coronary spasm. They may be supplemented with parenterally administered nitroglycerin if needed. Calcium channel antagonists are also given before PTCA and usually for approximately 2 weeks after the procedure. After the patient is dismissed from the hospital, aspirin is usually given long term.

4 568 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 either alone or in combination with other antiplatelet agents. Selection of Patients. Single-Vessel Disease. ^Patients with single-vessel disease still constitute a large percentage of those who undergo PTCA.^ The category of single-vessel disease, however, encompasses a large number of different patient subsets.'* Dilation is no longer confined to single, discrete subtotal proximal stenoses but is now used in patients with more diffuse or distal stenoses, lesions involving branch vessels, and chronic occlusions. In addition, PTCA is performed in patients with singlevessel disease who have acute ischemic syndromes unstable angina, acute myocardial infarction, or postinfarction angina as well as in patients with stable angina or patients without symptoms but with substantial ischemia.'^'2'-27 Finally, PTCA is performed in patients with single-vessel disease who have a wide range of ventricular function, from normal left ventricular anatomy and function to considerably depressed left ventricular function. Currently, PTCA is used widely in various subsets of patients with single-vessel disease provided the lesion can be reached and dilated and provided the patient has provokable ischemia or a large amount of myocardium at risk for example, disease of the proximal left anterior descending coronary artery. Many patients who undergo PTCA for singlevessel disease could be managed medically and have an excellent outcome. Application of dilation in these patients involves analysis of the safety and efficacy of the procedure, the patient's desires and expectations, and the potential for restenosis and its implications. Currently, many patients with provokable ischemia and a highgrade single arterial stenosis would prefer PTCA to medical or surgical therapy. A randomized trial of PTCA with medical therapy for singlevessel disease is currently under way (the Veterans Administration ACME [Angioplasty Compared to Medicine Evaluation] Study). The success rates of dilation in patients with single-vessel disease depend on the details of the coronary anatomy. In patients with a proximal, concentric subtotal stenosis, dilation should be successful in 95% of the cases (Fig. 1). In patients with less ideal anatomy, success rates are lower.^^'^^ The lowest success rates occur in patients with chronic occlusions. In these patients, if the occlusion has been present for more than 3 months and is long, the chances of successful dilation are less than 50%.^ '^^ Dilation may still be attempted if the patient has poorly controlled ischemia provided the patient and referring physician understand the reduced success rates. Most patients who undergo PTCA would be classified between these two extremes, and the success rates would vary accordingly. In these patients, one or more adverse angiographic factors are typically present. In this diverse patient group, unless there is a reasonable expectation of success (85% or more), our laboratory would not usually attempt dilation. The exception to this guideline in patients with chronic stable angina would be those with singlevessel disease, incapacitating sjonptoms, and severe ischemia, in whom surgical treatment is necessary. In these patients, even if the chance of successful dilation is less than 85%, dilation is often attempted to avoid or delay the need for a coronary artery bypass grafting procedure. In patients with single-vessel disease and acute ischemic syndromes, PTCA can be performed with success rates similar to those in patients with chronic stable angina. ^^'^' The hallmarks of the arterial pathologic changes in these patients are plaque fissuring and coronary thrombus (Fig. 2).^^^" This underlying unstable arterial pathologic condition predisposes to occlusion during PTCA or to reocclusion after initially successful dilation.^^'^* This outcome can usually be managed with repeat dilation. In such patients, adjunctive treatments such as antiplatelet agents, anticoagulants, and even lji;ic therapy may play a more important role than in patients with stable angina. A special circumstance is acute myocardial infarction (Fig. 3). In these patients, the typical angiographic finding is acute thrombotic occlusion of the infarct-related artery. PTCA may be used alone to disperse the thrombus mechanically and treat the underlying atheromatous lesion. It is successful in 85 to 90% of patients. More commonly.

5 Mayo Clin Proc, April 1990, Vol 65 INTERVENTIONAL CARDIOLOGY 569 Fig. 1. Angiographic anatomy ofthe first patient who underwent percutaneous transluminal coronary angioplasty at the Mayo Clinic. A, Ideal anatomy for dilation was present at baseline (arrow). B, After dilation, an excellent result was achieved. (From Holmes and Vlietstra.^) because of the logistics of urgent catheterization during acute myocardial infarction, lytic therapy is administered first. In these patients, if recombinant human tissue-type plasminogen activator (rt-pa) is used and reperfusion is successful, it is best to delay PTCA for at least 18 to 48 hours or even longer unless ischemia recurs.23'2*'26'»o This approach is associated with better success rates and fewer complications than successful rt-pa therapy followed by immediate PTCA. Presumably, the delay allows some stabilization of the underljdng unstable arterial pathologic condition. In patients in whom lytic reperfusion fails, r*tca can be used as a means of "rescue" reperfusion.*' In this setting, success rates are lower (70 to 75%), but when successful, such rescue or salvage angioplasty may be associated with improved outcome (although the available data are limited).*^*^ The exact role of rescue angioplasty must be evaluated further. Multivessel Disease. The largest increase in the number of dilation procedures has resulted from use of the technique in patients with multivessel disease (Fig. 4).2'''* *' This application of PTCA is controversial. Patients with multivessel disease have a poorer event-free survival in comparison with patients with singlevessel disease. Important considerations before performance of PTCA in these patients include the risk-to-benefit ratio, the ability to achieve complete revascularization, and restenosis. The risk-to-benefit ratio must take into account specific anatomic features as well as the Fig. 2. Right coronary angiogram in a patient with unstable angina, showing severe stenosis and intracoronary thrombus. (From Holmes and Vlietstra.^)

6 570 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 Fig. 3. A, Angiogram of patient with acute anterior infarction, occlusion of left anterior descending coronary artery, and intracoronary thrombus. B, After dilation, improvement was evident. (From Holmes and Vlietstra.^) presence and degree of left ventricular dysfunction. One discrete noncalcified stenosis in each of two major epicardial coronary arteries may be associated with less risk than attempted dilation of a diffusely diseased calcified segment that involves only one artery. The National Heart, Lung, and Blood Institute PTCA Registry offers some multicenter data on the risk of complications associated with PTCA performed during 1985 and ' Since that time, catheter designs have continued to be modified, but trends in complications should still be similar. Overall hospital mortality was low but did depend on the extent of vessels diseased. The mortality was 0.2% for single-vessel disease, 0.9% for two-vessel disease, and 2.2% for threevessel disease. When a combined endpoint of death or emergency coronary artery bypass operation necessitated by nonfatal infarction was considered, a similar dependence on the extent of coronary artery disease was noted: 5.5% for single-vessel disease; 8.1% for twovessel disease; and 9.3% for three-vessel disease. The use of new technologic systems such as prolonged dilation perfusion catheters, other "bailout" catheters, and intra-arterial stents and new surgical techniques should help to make dilation safer and more reliable. A second major consideration before PTCA in patients with multivessel disease is the ability to achieve complete revascularization.''^ The importance of complete revascularization has been emphasized in some published surgical series.'^" In those series, complete revascularization was associated with improved patient outcome. Nonetheless, the independent importance of complete revascularization has been debated.**some investigators maintain that failure to achieve complete revascularization identifies a patient population with more severe and extensive disease than others. If that is the case, patients with incomplete revasculariza- Fig. 4. Patient with multivessel disease who underwent percutaneous transluminal coronary angioplasty. Eccentric stenosis of circumflex artery (A) had an excellent response to dilation (B). Stenosis in middle left anterior descending coronary artery (C) similarly responded to dilation procedure (D). Finally, occluded right coronary artery (E) was dilated. Although artery is patent after dilation (F), diffuse disease remains.

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8 572 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 tion may have a poorer outcome not because of the degree of revascularization but by virtue of more severe underlying disease. This concept has particular importance for patients who undergo PTCA. Of patients with multivessel disease who currently undergo PTCA, complete revascularization is achieved in only a minority. This result is usually related to the presence of an old occlusion that cannot be dilated. Although complete revascularization makes intuitive sense, the need to achieve it in actual practice is less certain. In the patient with multivessel disease, if a single culprit lesion can be identified and dilated successfully, the outcome may be excellent. In our experience, if complete revascularization can be achieved with PTCA, patients have an improved outcome.'"' Therefore, in patients with multivessel disease, PTCA is considered a good option if all significant lesions are suitable for dilation. In some patients with an obvious culprit lesion for example, a patient with angiographically confirmed multivessel disease but stable symptoms in whom unstable angina and a new lesion subsequently develop PTCA is also done.^^ At our institution, of patients with multivessel disease who need a revascularization procedure, PTCA is chosen in approximately 30% and a coronary artery bypass operation is done in approximately 70%. Restenosis is the third issue of particular importance in patients with multivessel disease.^'*"^" Restenosis has been refractory to preventive measures. In published series, restenosis rates have averaged 30%, predominantly in patients with single-vessel disease. In patients with multivessel dilation, restenosis rates are higher. Although multiple intervention trials have been published, including studies with aspirin and dipyridamole, warfarin, corticosteroids, prostacyclin, and calcium channel blockers, none has been associated with a reduction in restenosis rates. Recently, a fish oil trial in a series of 82 patients who had undergone coronary angioplasty showed a reduction in restenosis rate from 36% in the control group to 16% in the treated group.^^ This finding has not been confirmed in a larger series of patients. Other strategies are needed. It can be anticipated, however, that resolution of the problem of restenosis will increase the frequency with which dilation is performed. The application of PTCA to multivessel disease has generated a considerable amount of interest. Defining the optimal role of the procedure is important because of the large number of patients who undergo revascularization and the potential cost implications. Currently, two large randomized trials, the Emory Angioplasty Surgery Trial (EAST) and the Bypass Angioplasty Revascularization Investigation (BARI), are enrolling patients. These studies will compare dilation versus coronary artery bypass operation in randomized patients. Although the primary aim is to compare the mortality associated with the two treatment strategies, a secondary aim will be to identify those subsets of patients in whom dilation is a reasonable revascularization alternative and those in whom a coronary artery bypass grafting procedure is more optimal. In addition, these investigations may identify patients in whom either procedure can be reasonably expected to yield excellent results. The outcome of these studies will be important in planning optimal patient care with use of cost-effective revascularization strategies. NEW INTERVENTIONAL PROCEDURES The widespread application of PTCA has stimulated interest in other interventional procedures for the treatment of coronary artery disease including atherectomy, intracoronary stents, and laser. These modalities remain investigational but hold promise for the treatment of complications of dilation and perhaps the prevention of restenosis. Atherectomy. Of the current new procedures, in the United States the most experience has been gained with atherectomy. As the name implies, atherectomy involves actual removal of plaque tissue. The most advanced device, from a regulatory viewpoint, is the Simpson Atherocath (Devices for Vascular Intervention, Redwood City, California) (Fig. 5). This system has a side window that is positioned toward the

9 Mayo Clin Proc, April 1990, Vol 65 INTERVENTIONAL CARDIOLOGY 573 MotortzRl cmtar Fig. 5. Diagram of atherectomy catheter in proximal left anterior descending coronary artery (see text for discussion). plaque and a rotating cutter cup that shaves off plaque material. The cutter, which has a battery-operated motor, rotates at 2,500 rpm and is advanced manually. An inflatable balloon presses the side window firmly up against the plaque. As atheroma is collected, it is stored in the distal housing of the cutter capsule. Directional repositioning (by rotation of the catheter) allows radial excision of the plaque. This device is more thoroughly discussed in a previous article by Kaufmann and associates.'^* Coronary atherectomy with the Simpson Atherocath has been done in approximately 1,000 patients in the United States. Its use has been restricted to one or two native or recurrent subtotal stenoses in proximal, large, nontortuous vessels. Success rates of approximately 85% have been achieved. Most lesions approached have been in the proximal left anterior descending and proximal right coronary arteries or in bypass graft stenoses. Many of these initial patients had undergone prior dilations, although an increasing number are undergoing treatment for native, previously undilated stenosis. In patients who have undergone the procedure, the typical arteriographic finding postoperatively is a smooth surface with less residual stenosis in comparison with conventional PTCA^'' (Fig. 6). Abrupt reclosure of these segments in the early postprocedure period seems to be decreased in comparison with such occurrences after conventional balloon angioplasty.**" At the Mayo Clinic, approximately 130 patients have been treated with this device. Satisfactory opening of the lesion (by more than 40% of the luminal diameter narrowing) has been achieved in approximately 85% of these patients. The procedure has been applied in native lesions and also within coronary vein grafts. In approximately 25% of the procedures, adventitial tissue is removed at the time of atherectomy. This technique has not resulted in an adverse short-term outcome. The long-term follow-up results in these patients are being accumulated. Follow-up angiography is being performed in all patients at 6 months after atherectomy. Restenosis rates are similar to those seen for PTCA. Whether this result is attributable to too extensive tissue resection remains to be determined. The device is being modified to produce less dilation effect. In addition, more selective removal of just the atherosclerotic plaque is being attempted. Even though the atherectomy devices are improving with successive modifications, they are still large, are rather inflexible, and require an 11-F sheath for placement. Further advances in technology should help, although with continued miniaturization, the volume of plaque material removed with each pass may decrease; therefore, more passes may be necessary. Several other rotating, abrasive or cutting devices are under evaluation. Some of these devices use low-speed rotation, and others use more rapid rotation. Some allow for aspiration of the debris, whereas others fragment the material into tiny pieces that are embolized distally.^'' ^ -phe latter type does not actually accomplish "atherectomy" but rather achieves angioplasty combined with "atheroembolism." The potential deleterious effects of such atheroembolism may limit the application of this type of device."-^ One novel low-speed (up to 200 rpm) device has generated considerable attention. Designed by Kaltenbach and colleagues in Frankfurt, West Germany, it consists of a power-driven, rotating guide wire that can be used to perforate chronic

10 574 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 Fig. 6. A, Stenotic lesion in proximal left anterior descending coronary artery. B, After atherectomy, minimal residual stenosis is present. total obstructions in the peripheral or coronary arteries."'' Clinical trials of this new system are likely to begin shortly in the United States. The exact role of all these devices remains undetermined. The concept of removal of atheromatous material, rather than merely "rearranging" it as is done with balloon angioplasty, remains extremely attractive. One valuable aspect of atherectomy is the availability of restenotic plaque material for histologic examination. It is now clear that restenosis after PTCA is due to an intense fibrocellular proliferation. This knowledge has stimulated a new avenue of research and attempts to prevent restenosis. Systemic or locally administered growth-inhibiting agents show promise.""^ Intracoronary Stents. The persistently limiting features of PTCA include (1) the 5% incidence of acute dissection and abrupt closure of the vessel that usually necessitate emergent surgical revascularization and (2) a 30% incidence of symptomatic restenosis that has been refractory to a variety of pharmacologic agents. The insertion of an intracoronary stent at the site of PTCA is a strategy designed to support the disrupted plaque and intimal layer mechanically to prevent acute closure after dissection. Additionally, the homogeneous radial stress circumferentially applied to the vessel wall with the stent would provide a smoother surface and more concentric dimension to the intraluminal aspect of the vessel after PTCA. The consequence of improved flow because of less turbulence and better rheologic characteristics might be expected to result in more favorable healing and endothelial overgrowth at the site of PTCA and thereby lessen the incidence of restenosis. The intracoronary stent design that has been used most frequently in the clinical setting to date (Fig. 7) was implanted in more than 150 patients in Europe during a 2-year period."" This device consists of a woven wire mesh configuration made from a stainless steel alloy. The mesh design, which incorporates 16 filaments with a standard diameter of 0.09 mm, varies in length from 15 to 23 mm. This design readily allows elongation of the stent to fit snugly over the end of a delivery catheter that is 1.6 mm in diameter. The stent is contained by a sleeve that extends the length of the catheter. This catheter facilitates delivery of the stent to the desired

11 Mayo Clin Proc, April 1990, Vol 65 INTERVENTIONAL CARDIOLOGY 575 Fig. 7. Intracoronary stent and delivery system being tested widely in Europe. The stent is contained by a sleeve that extends the entire length of the catheter. Thus, delivery of the stent is facilitated. (From Sigwart and associates.*^** By permission of The New England Journal of Medicine.) intracoronary position over any standard PTCA guide wire. The usual circumstance that would lead to use of this stent would be an undesirable result after PTCA as a consequence of either abrupt vessel closure from dissection or persistence of the primary stenosis despite multiple attempts at dilation. The guide wire would be left in place across the site of the PTCA, the balloon removed over an extension wire, and the stent-bearing delivery catheter then advanced over the wire to the desired position. The metallic design allows visualization of the stent with use of fluoroscopy. After the stent has been positioned satisfactorily with the catheter, the sleeve is withdrawn and the stent expands with a distal to proximal release. It is extremely important to deliver the stent precisely to the desired site because the stent cannot be retrieved once it has been released. The stent selected for delivery should be 0.05 mm larger than the measured diameter of a normal segment of the vessel adjacent to the site of the stenosis to allow optimal self-expansion of the stent, to provide the radial stress necessary to buttress the dissected plaque, and to achieve a caliber that approaches that of the adjoining normal segment of vessel. Quantitative angiographic measurements have substantiated improved geometry of the stenotic area with use of this stent.**' In a recent analysis of 120 patients, the area of stenosis improved from 82% before PTCA to 59% after PTCA and then to 39% after placement of a stent. When reevaluated angiographically 24 hours later, this area of stenosis was, in fact, reduced by another 10% because of continued radial expansion of the stent. The "Swiss kiss" is a recent adjunctive maneuver in which, after delivery of the stent, the delivery catheter is exchanged for a balloon catheter, which is positioned inside the stent and expanded to the measured dimensions of the adjoining normal vessel segment.*** This maneuver facilitates further expansion of the stent to its maximal overall caliber but also serves to embed the metal filaments deeper into the arterial wall, theoretically to lessen the area of metal material exposed for potential thrombogenesis. This technique reduces the area of stenosis by an additional 10%. Other metallic stent designs are currently in the initial stages of implantation in clinical investigational trials (Fig. 8). One other design uses a different mesh configuration made of a stainless steel alloy that substantially lessens the free space-to-metal ratio of the stent such that the metallic portion constitutes 30% of the area of the stent.'" Thus, the possibility of thrombosis on the metallic material may be decreased. This design has an articulation point in the center of the 15-mm-long stent to optimize the fit in tortuous arterial segments. This stent design is not self-expanding but rather is collapsed over a deflated PTCA balloon, which then is inflated to the exact dimension desired. The major difficulty with this design is the potential for dislodgment of the stent from the balloon catheter during delivery to the placement site. Experience has developed with use of this Schatz- Palmaz stent in more than 200 patients. The initial results with use of single stents have been encouraging. A third metallic design incorporates a single helical coil with interlocking connections at alternating sites. This stent is constructed from a tantalum wire that enhances strength and may decrease thrombogenicity. The stent is wrapped around a deflated PTCA balloon and may be

12 576 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 Fig. 8. Alternative stent configuration currently being evaluated as a "bailout" device if acute occlusion occurs and also as adjunctive therapy in patients at increased risk of occlusion. more stable than other designs during delivery as a consequence of the helical shape. Still another metallic design involves a series of six to eight parallel wires composed of a stainless steel alloy with the ends of the wires alternately connected. This design is loaded within the tip of a catheter delivery system that allows placement of a guide wire through the lumen of the catheter and stent. A small plastic tube is deployed behind the stent within the catheter to attempt to hold the stent in the desired position while the outer catheter is withdrawn. This stent design has the maximal radial expansile strength, but the delivery of the stent is less exact than with the other designs. Also, the delivery catheter is rigid and difficult to deploy in tortuous arterial segments. The predominant acute complication that can affect all the metallic stents is closure from thrombosis, which may occur in approximately 5% of implanted stents. This number is gradually diminishing from the initial reports of 8 to 10% as a consequence of the "Swiss kiss" technique to embed the metal filaments deeper in the vascular wall and from refined anticoagulation regimens. These regimens vary from device to device. Current anticoagulation regimens involve aggressive heparinization to achieve a partial thromboplastin time of 80 to 120 s for up to 4 days after implantation of the stent and conversion during that time to sodium warfarin anticoagulation that is continued for 6 months. All patients are treated additionally with an antiplatelet regimen that includes aspirin alone or in combination with orally administered dipyridamole or sulfinpyrazone (or both). Intracoronary administration of urokinase as lytic therapy has also been used in conjunction with implantation of some stents. The initial 6-month follow-up of stent implantation in the European Cooperative Trial involving 60 patients was disappointing in that the overall restenosis rate was approximately 33%, which is comparable to that found after PTCA alone (Serruys PW: Personal communication). Further clinical assessment of larger numbers of patients is clearly necessary to confirm this percentage. A stent barrier may not be sufficient to suppress restenosis. Stent design is becoming more sophisticated to the extent that these devices may more appropriately be termed endoprostheses. The direction of future research is the manufacture of stents consisting of polymeric materials that offer enhanced conformability to the contours of the vessel. These materials also should impose less stress at the interface of the distal ends of the stent with a normal adjoining coronary artery. The continual epicardial motion of the coronary vasculature may apply constant stress at the ends of the rigid metallic stents to the degree that fibrosis and stenosis may progress at this interface or the distal ends could conceivably erode through the vessel wall and cause perforation. An ideal solution to this scenario would be the use of a polymeric stent that could be absorbed after subintimal dissection planes have healed and endothelial overgrowth has been completed several months after implantation. Another advantage of the polymeric materials would be the potential for the bonding of anticoagulants such as heparin to decrease the occurrence of thrombosis and pharmaceutical agents that could be gradually eluted to inhibit

13 Mayo Clin Proc, April 1990, Vol 65 INTERVENTIONAL CARDIOLOGY 577 the process of restenosis or possibly augment the reendothelialization of the vessel. Lasers. The use of lasers in the treatment of coronary artery disease holds significant promise because atherosclerotic plaque can be vaporized and removed. The application of lasers to the cardiovascular system has been limited, however, because of technologic problems stiffness of the optical fibers, lack of control of the ablation process, nonselectivity of ablation, and thermal effects on nontarget tissue. Several of these problems have been addressed, and laser therapy has been used in fairly large numbers of patients with peripheral vascular disease. The application of lasers for the treatment of coronary artery disease has evolved more slowly because of concerns about safety but also because of the technical and technologic problems of working in curved, sometimes tortuous, vessels in the beating heart. In general, two broad applications have developed in the use of lasers for the treatment of cardiovascular disease plaque-vessel wall interactive and photoablative techniques. Plaque-Vessel Wall Interaction. Early experience with experimental studies clearly showed that passing a bare optical fiber down a vessel was fraught with hazards because of the potential for perforation by the fiber or perforation because of nonselective and uncontrolled photoablation.^' As a result, the tip of the optical fiber was modified by placing an ovoid metal cap on the end and creating a thermal probe or "hot tip" (Fig. 9). The shape of the metal cap not only diminished the possibility of vessel perforation during fiber motion but also allowed the thermal energy of the laser to be circumferentially distributed; thus, better control of the thermal effects was possible. Atherosclerotic plaque is vaporized and undergoes thermal compression by contact with the thermal probe as it is advanced down the artery. The lumen created is as large as the size of the ovoid cap. This method has been used successfully in treating stenoses and occlusions in the peripheral circulation. In the largest published series, a 100% success rate was achieved in the treatment of stenotic lesions less than 7 cm in length. For short occlusions Fig. 9. Various "hot tip" lasers are available. These designs have been used in an attempt to overcome the problem of perforation that can occur with bare fibers (see text for details). (Photograph courtesy of Trimedyne, Inc., Santa Ana, California.) (less than 3 cm), the success rate was also 100%. In occlusive lesions that exceeded 7 cm, the success rate was 81%. The 1-year cumulative patency rate for stenotic lesions was 95% and for occlusions was 76%.''^ These results compare favorably with those for balloon angioplasty alone. The "hot tip" method has been used in a few small series in the coronary circulation; arterial perforation was a major problem.''^'^* In addition, the "hot tip" has been ineffective in crossing or dilating calcified lesions.'^ Furthermore, in the presence of calcified lesions, the temperature of the surrounding tissue is greatly increased. Second- and third-generation thermal probes have been developed and are being subjected to early clinical trials in the coronary circulation. Further testing will reveal how these newer probes will perform in the coronary system. A second plaque-vessel wall interactive method is the laser balloon angioplasty system developed by Spears^" (Fig. 10). This technique uses a modified PTCA catheter that contains an optical fiber. The portion of the fiber inside the balloon is polished so that when laser energy is directed down it, laser light is radiated 360 degrees. With use of this method, PTCA is

14 578 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 Fig. 10. Diagram of a laser balloon angioplasty system in which a modified percutaneous transluminal coronary angioplasty catheter contains an optical fiber. This device can be used for thermal sealing. (Photograph courtesy of USCI, Inc., Billerica, Massachusetts.) performed in a standard fashion. If the results are judged acceptable angiographically, the catheter is repositioned across the area of dilation, and the balloon is reinflated. At this time, the laser is turned on and the area of dilation is exposed to laser irradiation. This portion of the artery is thermally sealed, and dissection clefts are welded back down to the vessel wall. As a result, the intimal surface may be less thrombogenic, and because the artery was welded with the balloon inflated, elastic recoil may be eliminated. Initial clinical trials are under way, and it is hoped that these effects will substantially reduce the rate of restenosis in comparison with standard PTCA. Photoablation. Safe photoablation of atherosclerotic plaque has presented many problems, several of which have been overcome. One system uses a modified PTCA approach. With this method, the balloon catheter is advanced to the lesion of interest by using a standard guide wire. The guide wire is removed and replaced with an optical fiber with a sapphire lens on its tip. The sapphire lens increases the angle of divergence of the laser beam. Two effects are achieved: (1) a larger area of tissue ablation and hence a larger channel in the obstruction is created and (2) because of divergence of the beam, the further from the tip of the fiber, the lower the laser energy. Thus, tissue remote from the target will not receive enough laser energy to cause photoablation (although nontarget tissue will still become heated because of the laser energy). This problem of heat has been surmounted by flushing saline or Ringer's solution down the balloon catheter. Once the balloon and optical fiber are positioned appropriately, the balloon is inflated to align the optical fiber in a coaxial orientation with the vessel. Flushing is then begun, and the laser is activated. Multiple laser applications with 10 W for 1 to 2 seconds are performed. The balloon is deflated and advanced, repositioned, and the sequence is repeated until a channel has been created through the lesion. Once through the lesion, the optical fiber is exchanged for a standard guide wire, and balloon dilation is performed. This method has been used successfully in the peripheral circulation, with a 100% success rate in stenotic lesions and a 91% success rate in occlusions.'' The overall patency at 6 months was 70%. Complications that were encountered included embolization, thermal perforation, thrombosis, and spasm. A second photoablative method consists of using a multifiber bundle with or without a central guide wire (Fig. 11). With this method, the optical bundle is advanced to the site of the lesion, the individual fibers are targeted, and laser energy is delivered in short pulses sequentially down each fiber. In our first eight percuta-

15 Mayo Clin Proc, April 1990, Vol 65 INTERVENTIONAL CARDIOLOGY 579 Optical «ΙιΙβΙιΙ Optical bundl* L_ 0 Multlflb«r bundle Fig. 11. One alternative photoablative approach for treatment of atherosclerotic disease with use of a multifiber bundle. (From Bresnahan DR: Lasers in cardiovascular disease. In Interventional Cardiology. Edited by DR Holmes Jr, RE Vlietstra. Philadelphia, FA Davis Company, 1989, pp ) neous intracoronary cases performed with an excimer laser, successful laser ablation was achieved in each. This system can be used with either a pulsed or a continuous-wave laser, and by restricting the pulse duration for each fiber, collateral damage to nontarget tissue is minimized. In addition, some systems use a feedback mechanism whereby low-energy laser light is reflected off the tissue and undergoes spectral analysis. ^'' ''^ Results of this analysis are used to characterize the tissue as either normal or atherosclerotic before high-level laser energy is used for ablation. Such a "probe and fire" system has been used successfully to recanalize the superficial femoral artery in humans.''* Clinical trials of this system in the coronary arteries have just begun. To date, we have performed this procedure in 70 patients with coronary artery disease, and the success rate has been 85%. CONCLUSION The future for interventional cardiology continues to broaden. PTCA will remain of central importance and will allow many patients to have nonsurgical revascularization. Dilation, however, has been unable to address certain problems. Four specific areas remain. 1. Old Chronic Occlusions. Because success rates with conventional dilation of totally obstructive lesions are low and restenosis rates are high, surgical revascularization is necessary in many patients. To date, attempts to increase the success rate have been limited. The role of new devices to solve this problem remains uncertain; a laser-type device that could be used to identify plaque reliably, distinguish it from vessel wall, and then selectively ablate the plaque material would be ideal. Rotational atherectomy also has potential but will remain limited because of its nonselective nature. 2. Diffuse Disease. In patients with diffuse vascular disease, conventional dilation has been of limited value. Laser ablation or certain configurations of atherectomy show considerable promise, particularly the former. Resolution of this problem will considerably increase the number of patients who could potentially undergo dilation. 3. Restenosis. Recurrence of stenoses after PTCA has both financial and medical implications, in that it reduces the initial cost savings from dilation and imposes increased morbidity related to the need for subsequent hospitalizations and procedures. More information is needed to identify preventive strategies. Lesion debulking with laser therapy or atherectomy has intuitive appeal; whether this approach will be safe and effective is unclear. Stents that can serve as a scaffolding and also be used to deliver local agents remain an intriguing technology. Biochemical approaches with selective drugs perhaps have the most potential to solve the problem of restenoses. Resolution of this problem might initially decrease the number of dilation procedures needed, inasmuch as a substantial number of such procedures are currently performed to treat restenosis. Eventually, however, resolution will extend the application of dilation. 4. Abrupt Closure After PTCA. Although abrupt closure after balloon angioplasty occurs in only a few patients, it identifies a group with an increased frequency of infarction, need for urgent coronary surgical intervention, and death. Substantial strides have been made in treating this problem with use of stents, atherectomy, and laser in selected patients. Resolution or prevention of this problem will make conventional dilation procedures even safer and more widely applicable.

16 580 INTERVENTIONAL CARDIOLOGY Mayo Clin Proc, April 1990, Vol 65 Interventional cardiology remains an expanding discipline. Information about new devices and procedures is accumulating rapidly. The promise of improved patient care continues to provide the stimulus for further development of this field. REFERENCES 1. Griintzig AR, Senning A, Siegenthaler WE: Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. Ν Engl J Med 301:61-68, Holmes DR Jr, Vlietstra RE: Balloon angioplasty in acute and chronic coronary artery disease. 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