Excimer laser-assisted femoral angioplasty: Early results W a l t e r J. M c C a r t h y , M D , R o b e r t L. Vogelzang, M D , * Albert A. N e m c e k Jr., M D , * Allen Joseph, M D , * William H . Pearce, M D , William R. Flinn, M D , and J a m e s S.T. Yao, M D , P h i ) , Chicago, Ill. The ability to ablate atheroma without generating heat makes the excimer laser wavelength a promising intraluminal technique for the treatment of arterial occlusive disease. This series reviews a preliminary experience treating patients with superficial femoral arterial disease admitted with limb-threatening ischemia or claudication. Twenty-six diseased superficial femoral arteries (5 stenotic and 21 occluded) were treated in 23 consecutive patients. Patients with claudication (18) reluctant to undergo bypass or with limbthreatening ischemia (8) at extremely high risk for surgery were included. There were 10 men and 13 women with a mean age of 67 years. A 308 nm excimer laser with an over-the-wire catheter (19) or balloon-centered end-on catheter (7) was used followed by balloon angioplasty. Twenty-four procedures were performed percutaneously, and two were performed with the vessel open in the operating room. Technical success, defined as disobliteration confirmed by angiography and greater than 0.15 increase of the ankleforachial index, was achieved in 15 of 26. Eleven of 21 occlusions (52%) and four of five stenoses (80%) were opened. Only two of 11 lesions longer than 10 cm were successfully treated. Unsuccessful attempts (technical failure) occurred in 11 of 26 patients and resulted in four elective and one emergency femoral-popliteal bypass. Five patients were discharged with their daudication unchanged, and one had an elective amputation. Six arterial perforations with three arteriovenous fistulas occurred, all resolved without operation. No unanticipated limb loss occurred. In the 15 successful cases, the mean anlde/brachial index increase was 0.34. Seven (47%) of these 15 remain patent with a mean follow-up o f 9.5 months (1.5 to 14 months). Initial technical success and early patency of excimer laser angioplasty is poor compared to arterial bypass surgery. The technique has limited use for long stenoses or occlusions. However, it may be effective in carefully selected short lesions. (J VAsc SuRG 1991;13:607-14.)
Despite the success o f arterial bypass to relieve
ischemia of the extremities and the myocardium, less invasive percutaneous techniques are appealing. This basic premise has evolved since Dotter and Judldns ~ published the results o f simple arterial dilation for superficial femoral artery disease in 1964. The expansion o f this concept by balloon angioplasty o f both coronary and peripheral arteries was led by From the Division of Vascular Surgery of the Department of Surgery, the Feinberg Cardiovascular Research Institute, and the Department of Radiology,* Northwestern University Medical School, Chicago. Presented at the Fourteenth Annual Meeting of the Midwestern Vascular Surgical Society, Toledo, Ohio, Sept. 14, 1990. Supported in part by the Veterans Administration Research Service and the Division of Research Resources, National Institutes of Health (Grant no. RR00048), and the Alyce F. Salerno Foundation. Reprint requests: Walter J. McCarthy, MD, 251 E. ChicagoAve., Suite 626, Chicago, IL 60611. 24/6/27559
Gruentzig et al.2 and has changed the management of arterial disease in a significant way. It is to address the limitations of arterial balloon angioplasty that such devices as intraluminal lasers, heated probes, atherectomy devices, and ultrasound ablation catheters have been developed. Lasers of many varying wavelengths including argon, carbon dioxide, neodynium :yttrium-aluminum-garnet (Nd-YAG), and others have been reported for ablation of peripheral atherosclerosisY They all function by use of a thermal mechanism to vaporize or ablate occluding atherosclerosis. Although this mechanism may be effective, it is limited by inevitable thermal arterial injury, which may incite thrombosis and is known to cause vascular spasm. 6'7 The excinaer class of lasers promises a potential advantage by removing obstructive tissue without any significant thermal action. 8"9This mechanism, described as photochemical ablation, involves the breaking o f molecular 607
608 McCarthy et al,
bonds in tissue. In addition, the excimer wavelengths may have some advantage over others in the ablation of calcified material. The present study examines the clinical application of the first excimer laser available for extensive clinical study in peripheral arteries in the United States. This unit functions at 308 nm, providing energy to either a cylindrical over-the-wire catheter or one centered by a balloon for end-on application where a guide wire cannot be passed. Selection of patients early in the study was not guided by any practical clinical experience with this unit. Thus the treatment of lesions now known to be too long for any real hope of success was initially attempted. These failures helped to define the limits of the instrument and are included in the results. METHODS AND CLINICAL MATERIAL Over an ll-month period beginning in June, 1989, 26 superficial femoral artery lesions were treated in 23 patients by use ofexcimer laser-assisted balloon angioplasty at Northwestern Memorial Hospital, Chicago. This experience includes all patients treated with this technique, beginning with the initial individual. Three of the patients had both lower extremities treated. Their age ranged from 49 to 82 years (mean, 67), 10 were men and 13 were women. This study was part of a Federal Drug Administration Phase II program and was approved by the hospital institutional review board. All patients signed specific consent agreements. The patients participating in this study were selected from two distinct groups. Seventeen patients with limiting claudication affecting 18 limbs chose percutaneous therapy in an effort to avoid bypass surgery. Six patients with limb-threatening ischemia involving eight legs, one with rest pain and seven with gangrene or foot ulceration, were selected as being extraordinarily poor risks for anesthesia. All patients underwent Doppler ankle blood pressure evaluations before the procedure, with indexes ranging from 0.10 to 0.68 (mean, 0.49). Four patients with uncompressible ankle pressure were excluded from this mean. Diagnostic aortography was performed in all cases to delineate disease. This revealed superficial femoral artery occlusion in 21 and 5 limbs with stenoses of that artery. Lesions were divided by length into 12 short (=< 5 cm), 3 medium ( > 5 to 10 cm), and 11 long ( > 1 0 cm). Laser and laser catheters An ultraviolet xenon chloride pulsed 308 nm excimer laser was used as an energy source (Advanced
Journal of VASCULAR SURGERY
Interventional Systems, Irvine, Calif.). This magnetically switched unit uses 200 nsec pulses at between 10 and 40 Hz. Three different catheters were used, two for over-the-wire use and one capable of channeling through occluded vessels without guide wire direction. For vessel occlusion, a 7F balloon catheter with a 2 cm by 4 to 7 mm balloon was used to centrally position a 600 ~m single fiber 3.3F (1.1 mm) fiberoptic tip. The balloon was inflated to coaxiaUy stabilize the laser fiber, which was passed through its center. Two over-the-wire fibers were used. A 6.6F (2.2 mm) device composed of multiple separate fibers was used over a 0.018 inch guide wire. A smaller 4.7F catheter was also used over a 0.018 inch wire. This device used twelve 200 ~tm fibers. With these catheters the maximum lumen generated with laser alone was 2.2 mm. All fiberoptics (Advanced Interventional Systems) were calibrated to emit 35 to 50 mjoules per mm 2 of energy, depending on the capability of the fiber used. Energy output at the fiber tip was calibrated at the beginning and completion of each procedure by a meter attached to the laser unit. Laser procedure Twenty-four procedures were performed percutaneously in the radiology suite. Two interventions required operative exposure in the operating room with arteriotomy for catheter access. The operating room procedures involved radiographic equipment capable of digital subtraction angiography and hard copy. In every case the ipsilateral femoral region was selected, and for percutaneous procedures, an 8F introducer was used throughout. A heparin bolus of 5000 units, was used before every procedure. In every case, even with arterial occlusions, an attempt was made to pass a guide wire and use an over-the-wire laser catheter. When an over-the-wire catheter was appropriate, the 0.018 wire was first positioned through the lesion, then the laser catheter was advanced to the proximal portion of the stenotic area (Fig. 1). The laser was activated, and the catheter was advanced by hand at a rate of less than 1 mm/second. Treatment pulses of 10 to 20 seconds were used. The slow advancement rate was in an effort to prevent "plowing" and to allow the laser to ablate tissue. After the stenosis was treated, fluoroscopic evaluation was used to determine the need for repeating the treatment, and two or three more catheter passages were usually used (Fig. 2). In all
Volume 13 Number 5 May 1991
Fig. 1. Superficial femoral artery stenosis ofa patient with claudication. cases balloon angioplasty was used after laser enlargement of an existing stenosis (Fig. 3). Balloons with 4 to 7 mm inflated diameters were selected on the basis of angiographic measurements. A 3.3F (1.1 mm) balloon-centered laser fiber was used for arterial occlusions (Fig. 4). In these cases, the balloon catheter was first positioned just proximal to the lesion in question. The laser fiber was then introduced and, under fluoroscopic control, advanced at a rate of less than 1 mm/second into the arterial occlusion. The laser fiber was never advanced more than 2 cm beyond the balloon catheter tip, in an attempt to limit perforation (Fig. 5). Once advancement had been made, the balloon was deflated and advanced over the laser catheter. The process was then repeated with laser catheter advancement, by use of the guidance of the adjacent balloon. After the occluded arterial segment was completely penetrated, a guide wire was used to
Excimer laserfemoral angioplasty 609
Fig. 2. This previously stenotic artery, seen in Fig. 1, was first traversed with a 0.018 guide wire and then a 2.2 mm over-the-wire laser catheter. The resulting lumen is sufficient to allow standard balloon angioplasty.
position a standard balloon angioplasty catheter for luminal enlargement (Fig. 6). Permanent radiographic hard copy of each step was procured, and at the termination of the procedure all introducer sheaths were removed. Heparin was not reversed after any procedure. The number of 200 nsec pulses was recorded and ranged from 540 to 9200 (mean, 3083). At a usual pulse rate of 30 Hz, this represents an actual laser on-time of 18 to 306 seconds. Patients were pretreated with 325 mg aspirin and maintained on aspirin, 325 mg daily, indefinitely. Only those with thrombotic complications were given heparin in the postprocedure period, and these patients were then converted to sodium warfarin (Coumadin) therapy if appropriate to maintain a prothrombin time 1.5 times control. Patients were
610 McCarthy et al.
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Fig. 3. This previously stenotic artery, seen in Figs. I and 2, now has a significantly improved lumen after laser angioplasty and standard balloon angioplasty.
Fig. 4. Superficial femoral artery occlusion of a patient with foot gangrene.
evaluated with Doppler ankle/brachial index measurements in the immediate postprocedure period, after 24 hours, 2 weeks, 4 weeks, 3 months, 6 months, and will be studied each year. Initial success was defined as an anatomically patent vessel with corresponding ankle/brachial index rise of at least 0.15 or an appropriate change in arterial wave for patients with calcified vessels.
no failures, and long lesions ( > 10 cm) were successfully treated in only two (22%) with nine failures (Table I). Technical success could be further subcategorized by success in 11 of 21 total arterial occlusions and success in four of five stenotic lesions. The ability to pass a guide wire was a predictor of success, with 13 of 19 (68%) successful. This compared to only two of seven (29%) primary successes where an end-on, balloon-guided catheter was used for totally occluded vessels. The reasons for procedure failure are illuminating. Perforation occurred in six individuals, and of those, three developed arteriovenous fistulas with angiographic confirmation. In one patient because of distal embolization the procedure had to be terminated. In four patients the procedure was initially successful, but even after balloon angioplasty, the vessel immediately thrombosed. O f the 11 initial
RESULTS The effectiveness of this procedure is best demonstrated by defining the technical success rate with early patency and evaluating the patency of that subgroup. Initial technical success was achieved in 15 (58%) of the 26 lesions treated. Short lesions ( = 5 cm) were effectively opened in 10 (83%), with two failures. Medium-length lesions ( > 5 to 10 cm) were successfully opened in three cases (100%) with
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F~cimer laserfemoral angioplasty 611
Fig. 5. This occluded artery, seen in Fig. 4, was primarily opened with a balloon-oriented end-on catheter. The lumen was not sufficient but allowed standard balloon angioplasty.
Fig. 6. After balloon angioplasty, this previously occluded artery, seen in Figs. 4 and 5, had a diameter resembling the adjacent vessel.
technical failures, five patients elected to live with their claudication and were discharged from the hospital. Five individuals went on to femoral popliteal bypass to relieve claudication, and one of these required operation on an emergency basis the same day as laser angioplasty. This patient had increasing leg ischemia resulting from embolic occlusion of the below-knee popliteal artery. The embolus was removed at the time of bypass. One patient was deemed too medically unstable for operative intervention with bypass and after a period of stabilization underwent elective above-knee amputation. During the early follow-up to 14 months after technical success, 8 of 15 initially successful procedures failed (53%). These failures occurred between 10 days and 6 months after the initial procedure (mean, 3.2 months). In this group of eight, three had
elective femoral popliteal bypass with success. One elected no surgical intervention, and one underwent a successful atherectomy procedure with a rotary device, which is functioning 8 months after its completion. One patient who had bilateral procedures, both of which failed, was an elderly bedridden, patient on dialysis who had been previously deemed too ill to undergo surgical bypass. This patient eventually underwent bilateral below-the-knee amputations. Early patency has been achieved in 7 of the initial 15 successful cases (47%), with a mean follow-up of 9.5 months (1.5 to 14 months). Initial change in ankle/brachial index for the 15 initial successes documented a mean increase of 0.34 from 0.49 to 0.83. Two patients who had uncompressible tibial vessels were excluded from these calculations.
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612 McCarthy et al.
Table I. Initial technical success and failure Lesion Catheter length Immediate (cm) Over-the-wire Balloon-centered patency
Occlusion Short
MediLlnq
Long
Stenoses Short Medium
Long
1.0 1.2 2.5 3.0 3.2 4.0 4.0 4.0 4.4 4.5
X X X X X
X X
Yes Yes Yes Yes No Yes Yes Yes No Yes
5.1 8.7
X X
Yes Yes
11.5 13.5 14.0 15.5 17.0 17.5 17.5 18.0 30.0
X X
X X
Yes No No No No No No No No
3.5 5.0
X X
Yes Yes
7.5
X
Yes
20.0 27.0
X X
Yes No
X X X
X X X X X
Management of complications Although three of 26 limbs were lost to one above-knee and two below-knee amputations, none of these were unanticipated. All patients had been deemed too ill for surgical bypass should a percutaneous technique prove ineffective. Thus no limb loss was attributed to a worsened condition resulting from the laser angioplasty. Arterial perforation in the distal superficial femoral artery was observed in six cases, all of which resolved spontaneously without operative intervention. Three arteriovenous fistulas occurred as a result of these perforations, and they also resolved, as evidenced by follow-up angiograplay, without any intervention within i hour of their occurrence. Definite macroembolization to the popliteal level occurred in three patients. One resuited in treatment failure and a prearranged limb amputation. Another required emergency femoral popliteal bypass with embolectomy, and the third was successfully treated with urokinase therapy. Groin hematoma formation was evident in six patients, two of whom required operative intervention and arterial repair with local anesthesia. Four
other hematomas were minor and resolved without surgery. Distal superficial femoral and popliteal artery thrombosis developed in one patient during the procedure and was successfully treated with urokinase therapy. This patient remains in the early patency group.
DISCUSSION The initial success and early patency of patients treated with a 308 nm excimer laser and accompanying balloon angioplasty is disappointing. Only 15 of 26 patients had technical success. The length of arterial stenosis or occlusion correlated closely with the initial technical patency, and only two of nine (22%) lesions longer than 10 cm were successfully treated. This corresponds with success in 33% of lesions longer than 15 cm in recent work by Litvack et al.,~o who recorded the only other series of peripheral artery excimer laser angioplasty. In this series eight lesions were longer than 15 cm, only one of which was successfully opened. Long superficial femoral artery stenosis remains a challenge for percutaneous angioplasty, even if initial success is achieved. Murray et al." found a dismal 33.1% 6-month patency if lesions treated with balloon angioplasty alone were greater than 7 cm in length. ~1 In comparison, 6-month patencies of 93.7% were reported for shorter lesions. The initial technical success rate of 57% in the current study is lower than that of Litvack et al.,o (77%) but better than many other laser angioplasty reviews. Patient selection appears critical to define initial technical success rates. After gaining some experience in the Northwestern study, we avoided extremely long stenoses or occlusions, and initial technical results improved. Perforations of the artery had a profound impact on the technical success of this procedure. Six patients, 23% of the study group, experienced this difficulty, and each perforation required termination of the procedure. This rate is similar to the experience of Seeger et al?2 with 22% perforation in 10 of 46 arteries, using a heated tip sapphire lens instrument. Every perforation occurred in the lower superficial femoral artery at the adductor hiatus. Although three resulted in obvious arteriovenous fistulas, all six perforations proved completely benign and resolved without any operative intervention. Nevertheless, once perforation occurred, the chance of a successful recanalization was lost. Perforations occurred with the balloon-centered catheter five times and only once when an over-the-wire assembly was used. The propensity of the current system to perforate reflects the stiffness of the fiber and lack of any real tip
Volume 13 Number 5 May 1991
guidance. In this series the balloon-centered catheter was used seven times, with only two successes. However, in many cases these catheters opened an extended length of artery before finally being found outside the arterial lumen. Thus the problem is not an inability to penetrate occluded arterial tissue but rather guidance, and guidance may be the real limit of initial success with this laser. There was never any difficulty advancing the catheter in any of the 26 cases. The laser fiber could be passed with manual pressure and advanced with almost no tactile resistance even when radiographic calcified arteries were present. This is contrary to the experience with some existing laser units where lengthy exposure time is necessary for tissue ablation. Actual laser energy application time averaged 103 seconds (18 to 306 sec), and once the catheter was positioned this usually required 10 or 15 minutes of actual manipulation. Catheter-tip guidance has been addressed in other systems by measuring reflected radiation from a laser beam to differentiate diseased tissue from normal arterial wall. This concept seems conceptually sound but has been hard to apply clinically. ~s Other guidance systems are necessary, and external or intraluminal ultrasonic systems have been proposed. ~4 Early patency was seen in only 47% of the 15 patients in whom immediate technical success had been possible, with a mean follow-up of 9.5 months. This is less than the 71% reported by Litvack et al) ° with excimer lasers, also using a 9-month interval. The reason for this difference is uncertain in that the patient mix of Litvack et al. of stenoses and length of occlusions was similar to the present study. These patency rates are distinctly less than any reported surgical bypass at the femoropopliteal level. Complete arterial occlusions seemed most amenable to long-term success in the present study. Eleven of 15 initially successful lesions were complete occlusions, and seven (64%) of those remained patent at 9.5 months. Four of the initial technical successes were in vessels with stenoses, and none of that group remained patent at most recent follow-up. Five of the seven long-term successes are characterized by initial short occlusions with near-normal inflow and runoff patency. Two, however, represent successes in severely diseased arteries with runoff into blind popliteal segments. All occlusions developed in the first 6 months with a mean occlusion time of 3.2 months. This is similar to the pattern of early failure and then stability reported for long-term followup in coronary balloon angioplasty by Gruentzig et al. 2 where patency at 6 months after balloon
Excimer laserfemoral angioplayty 613
angioplasty heralded a good possibility of much longer patency. Although other laser wavelengths are capable of atherosclerotic ablation, excimer lasers may offer potentially greater clinical application, ls'16 Excimer lasers disobliterate even calcified plaque without creating significant thermal accumulation. 8"17Mechanistically, ablation is thought to be photochemical rather than thermal and allows excision of diseased tissue to take place at near ambient temperatures. The advantage of this characteristic has been used in ophthalmology for corneal surgery) 8 Application of excimer lasers to cardiovascular tissue was demonstrated by Isner et al. ~9 with the examination of excised coronary artery and cardiac valve tissue. Their study demonstrated a lack of coagulation necrosis as compared to thermal laser tissue interaction. This same group investigated ex vivo transmission of excimer energy through silica optical fibers to disobliterate atherosclerotic arteries and to interact in a fluid field. 2°'21 The observed low temperature cutting of excimer lasers initiated the theory of photochemical breaking of molecular bonds rather than the usual thermal degradation of tissue. However, some interesting speculation exists that the process may be thermally related. Clarke et al. 22 studied argon fluoride (193 nm) and xenon fluoride (131 nm) excimer lasers that were directed at samples of myocardium and atherosclerotic coronary artery segments. They used gas chromatography to evaluate degradation byproducts, and a series of short chain hydrocarbons were identified that are byproducts similar to those produced by flame-torching of similar tissue. This indirect evidence of at least a microscopic thermal mechanism is of interest. Steg et al.6 have compared contraction of vascular smooth muscle exposed to continuous-wave laser irradiation and excimer laser exposure. They conclude that excimer radiation does not cause the contraction of smooth muscle seen with other lasers but rather induces a "relaxation response." In the current series arterial spasm after laser fiber passage was not encountered. This advantage may be important in treating small vessels such as coronary and tibial arterial applications where transient spasm could cause procedural failure. In the present study despite the ability of the excimer laser to traverse all occluded arteries, a lumen diameter sufficient to be left without balloon angioplasty was not achieved. Therefore balloon angioplasty was used in every case to increase lumen diameter. This makes assessment of the excimer laser effect difficult. Given the lack of tissue heating, the
614
Journal of VASCULAR SURGERY
McCarthy et al.
core of the atheroma removed by the laser is comparable to a direct incision. Thus once a balloon angioplasty has taken place, the final luminal surface remains little influenced by the excimer laser. Extended patency then is as much a test of balloon angioplasty as it is of excimer laser energy. To truly evaluate this technology, catheters large enough to create lumens not requiring balloon angioplasty must be developed and tested. Angioplasty by use of balloon-assisted excimer laser is possible with immediate and early results dependent on the existing arterial pathology. Long stenoses and occlusions are uniformly unsuccessful when treated by this technique. In comparison, short arterial occlusions, even those accompanied by significant calcification, can be penetrated by the excimer laser and successfully dilated with balloon angioplasty. Therefore even in its primitive form, this laser provides potential above and beyond primary balloon angioplasty. However, the rates of both initial technical success and early patency are much lower than those of treatment with arterial bypass. Full evaluation awaits the development of larger laser catheters with some form of guidance to prevent arterial perforation. REFERENCES 1. Dotter CT, Judkius MP. Transluminal treatment of arteriosclerotic obstruction: description of a new technique and a preliminary report of its application. Circulation 1964;30: 654-70. 2. Gruentzig AR, King SP, Schlumph M, Siegenthaler W. Long-term follow-up after percutaneous transluminal coronary angioplasty: the early Zurich experience. N Engl J Med 1987;316:1127-32. 3. Nordstrom LA, Castaneda-Zuniga WR, Young EG, Von Seggern KB. Direct argon laser exposure for recanalization of peripheral arteries: early results. Radiology 1988;168:35964. 4. Michaels JA, Cross FW, Shaw P, et al. Laser angioplasty with a pulsed NdYAG laser: early clinical experience. Br J Surg 1989;76:921-4. 5. Vorwerk D, Zolotas G, Hessel S, Adam G, Guenther RW. Vascular tissue ablation by an Erbium-YAG laser: a fibertransmittable pulsed laser in the infrared range. Invest Radiol 1990;25:235-9. 6. Steg PG, Rongione AJ, Gal D, DeJesus ST, Clarke RH, Isner JM. Pulsed ultraviolet laser irradiation produces endotheliumindependent relaxation of vascular smooth muscle. Circulation 1989;79:189-97.
7. Haina D, Landthaler M. Fundamentals of laser light interaction with human tissue, especially in the cardiovascular system. Thorac Cardiovasc Surg 1988;36:118-25. 8. Cross FW, Bowker TJ. The physical properties of tissue ablation with excimer lasers. Med Instrumentation 1987;21: 226-30. 9. Wollenek G, Laufer G, Grabenwoger F. Percutaneous transluminal excimer laser angioplasty in total peripheral artery occlusion in man. Lasers Surg Med 1988;8:464-8. 10. Litvack F, Grundfest WS, Adler L, et al. Percutaneous excimer laser and excimer laser-assisted angioplasty of the lower extremities: results of initial clinical trial. Radiology 1989; 172:331-5. 11. Murray RR Jr, Hewes RC, White RI Jr, et al. Long-segment femoropopliteal stenoses: is angioplasty a boon or a bust? Radiology 1987;162:473-6. 12. Seeger JM, Abela GS, Silverman SH, Jablonski SK. Initial results of laser recanalization in lower extremity arterial reconstruction. J VAsc SURG 1989;9:10-7. 13. Laufer G, WoUenek G, Hohla K, et al. Excimer laser-induced simultaneous ablation and spectral identification of normal and atherosclerotic arterial tissue layers. Circulation 1988;78: 1031-9. 14. Yock PG, Linker DT. Intravascular ultrasound: looking below the surface of vascular disease. Circulation 1990;81:1715-8. 15. Isner JM, Rosenfield K, Losordo DW. Excimer laser atherectomy: the greening of Sisyphus. Circulation 1990;81: 2018-21. 16. Sartori M, Henry PD, Sauerbrey R, Tittel FK, Weilbaecher D, Roberts R. Tissue interactions and measurement of ablation rates with ultraviolet and visible lasers in canine and human arteries. Lasers Surg Med 1987;7:300-6. 17. Duda SH, Karsch KR, Haase KK, Huppert PE, Claussen CD. Laser ring catheters in excimer laser angioplasty. Radiology 1990; 175: 269- 70. 18. Seiler T, Bende T, Woilensak J, Trokel S. Excimer laser keratectomy for correction of astigmatism. Am J Ophthalmol 1988;105:117-24. 19. Isner JM, Donaldson RF, Deckelbaum LI, et al. The excimer laser: gross, light microscopic and ultrastructural analysis of potential advantages for use in laser therapy of cardiovascular disease. J Am Coil Cardiol 1985;6:1102-9. 20. Isner JM, Gal D, Steg PG, et al. Percutaneous, in vivo excimer laser angioplasty: results in two experimental animal models. Lasers Surg Med 1988;8:223-32. 21. Isner JM, DeJesus SR, Clarke RH, Gal D, Rongione AJ, Donaldson RF. Mechanism of laser ablation in an absorbing fluid field. Lasers Surg Med 1988;8:543-54. 22. Clarke RH, Isner JM, Donaldson RF, Jones G II. Gas chromatographic-light microscopic correlative analysis of excimer laser photoablation of cardiovascular tissues: evidence for a thermal mechanism. Circ Res 1987;60:429-37.
Submitted Oct. 9, 1990; accepted Oct. 19, 1990.
Despite the success o f arterial bypass to relieve
ischemia of the extremities and the myocardium, less invasive percutaneous techniques are appealing. This basic premise has evolved since Dotter and Judldns ~ published the results o f simple arterial dilation for superficial femoral artery disease in 1964. The expansion o f this concept by balloon angioplasty o f both coronary and peripheral arteries was led by From the Division of Vascular Surgery of the Department of Surgery, the Feinberg Cardiovascular Research Institute, and the Department of Radiology,* Northwestern University Medical School, Chicago. Presented at the Fourteenth Annual Meeting of the Midwestern Vascular Surgical Society, Toledo, Ohio, Sept. 14, 1990. Supported in part by the Veterans Administration Research Service and the Division of Research Resources, National Institutes of Health (Grant no. RR00048), and the Alyce F. Salerno Foundation. Reprint requests: Walter J. McCarthy, MD, 251 E. ChicagoAve., Suite 626, Chicago, IL 60611. 24/6/27559
Gruentzig et al.2 and has changed the management of arterial disease in a significant way. It is to address the limitations of arterial balloon angioplasty that such devices as intraluminal lasers, heated probes, atherectomy devices, and ultrasound ablation catheters have been developed. Lasers of many varying wavelengths including argon, carbon dioxide, neodynium :yttrium-aluminum-garnet (Nd-YAG), and others have been reported for ablation of peripheral atherosclerosisY They all function by use of a thermal mechanism to vaporize or ablate occluding atherosclerosis. Although this mechanism may be effective, it is limited by inevitable thermal arterial injury, which may incite thrombosis and is known to cause vascular spasm. 6'7 The excinaer class of lasers promises a potential advantage by removing obstructive tissue without any significant thermal action. 8"9This mechanism, described as photochemical ablation, involves the breaking o f molecular 607
608 McCarthy et al,
bonds in tissue. In addition, the excimer wavelengths may have some advantage over others in the ablation of calcified material. The present study examines the clinical application of the first excimer laser available for extensive clinical study in peripheral arteries in the United States. This unit functions at 308 nm, providing energy to either a cylindrical over-the-wire catheter or one centered by a balloon for end-on application where a guide wire cannot be passed. Selection of patients early in the study was not guided by any practical clinical experience with this unit. Thus the treatment of lesions now known to be too long for any real hope of success was initially attempted. These failures helped to define the limits of the instrument and are included in the results. METHODS AND CLINICAL MATERIAL Over an ll-month period beginning in June, 1989, 26 superficial femoral artery lesions were treated in 23 patients by use ofexcimer laser-assisted balloon angioplasty at Northwestern Memorial Hospital, Chicago. This experience includes all patients treated with this technique, beginning with the initial individual. Three of the patients had both lower extremities treated. Their age ranged from 49 to 82 years (mean, 67), 10 were men and 13 were women. This study was part of a Federal Drug Administration Phase II program and was approved by the hospital institutional review board. All patients signed specific consent agreements. The patients participating in this study were selected from two distinct groups. Seventeen patients with limiting claudication affecting 18 limbs chose percutaneous therapy in an effort to avoid bypass surgery. Six patients with limb-threatening ischemia involving eight legs, one with rest pain and seven with gangrene or foot ulceration, were selected as being extraordinarily poor risks for anesthesia. All patients underwent Doppler ankle blood pressure evaluations before the procedure, with indexes ranging from 0.10 to 0.68 (mean, 0.49). Four patients with uncompressible ankle pressure were excluded from this mean. Diagnostic aortography was performed in all cases to delineate disease. This revealed superficial femoral artery occlusion in 21 and 5 limbs with stenoses of that artery. Lesions were divided by length into 12 short (=< 5 cm), 3 medium ( > 5 to 10 cm), and 11 long ( > 1 0 cm). Laser and laser catheters An ultraviolet xenon chloride pulsed 308 nm excimer laser was used as an energy source (Advanced
Journal of VASCULAR SURGERY
Interventional Systems, Irvine, Calif.). This magnetically switched unit uses 200 nsec pulses at between 10 and 40 Hz. Three different catheters were used, two for over-the-wire use and one capable of channeling through occluded vessels without guide wire direction. For vessel occlusion, a 7F balloon catheter with a 2 cm by 4 to 7 mm balloon was used to centrally position a 600 ~m single fiber 3.3F (1.1 mm) fiberoptic tip. The balloon was inflated to coaxiaUy stabilize the laser fiber, which was passed through its center. Two over-the-wire fibers were used. A 6.6F (2.2 mm) device composed of multiple separate fibers was used over a 0.018 inch guide wire. A smaller 4.7F catheter was also used over a 0.018 inch wire. This device used twelve 200 ~tm fibers. With these catheters the maximum lumen generated with laser alone was 2.2 mm. All fiberoptics (Advanced Interventional Systems) were calibrated to emit 35 to 50 mjoules per mm 2 of energy, depending on the capability of the fiber used. Energy output at the fiber tip was calibrated at the beginning and completion of each procedure by a meter attached to the laser unit. Laser procedure Twenty-four procedures were performed percutaneously in the radiology suite. Two interventions required operative exposure in the operating room with arteriotomy for catheter access. The operating room procedures involved radiographic equipment capable of digital subtraction angiography and hard copy. In every case the ipsilateral femoral region was selected, and for percutaneous procedures, an 8F introducer was used throughout. A heparin bolus of 5000 units, was used before every procedure. In every case, even with arterial occlusions, an attempt was made to pass a guide wire and use an over-the-wire laser catheter. When an over-the-wire catheter was appropriate, the 0.018 wire was first positioned through the lesion, then the laser catheter was advanced to the proximal portion of the stenotic area (Fig. 1). The laser was activated, and the catheter was advanced by hand at a rate of less than 1 mm/second. Treatment pulses of 10 to 20 seconds were used. The slow advancement rate was in an effort to prevent "plowing" and to allow the laser to ablate tissue. After the stenosis was treated, fluoroscopic evaluation was used to determine the need for repeating the treatment, and two or three more catheter passages were usually used (Fig. 2). In all
Volume 13 Number 5 May 1991
Fig. 1. Superficial femoral artery stenosis ofa patient with claudication. cases balloon angioplasty was used after laser enlargement of an existing stenosis (Fig. 3). Balloons with 4 to 7 mm inflated diameters were selected on the basis of angiographic measurements. A 3.3F (1.1 mm) balloon-centered laser fiber was used for arterial occlusions (Fig. 4). In these cases, the balloon catheter was first positioned just proximal to the lesion in question. The laser fiber was then introduced and, under fluoroscopic control, advanced at a rate of less than 1 mm/second into the arterial occlusion. The laser fiber was never advanced more than 2 cm beyond the balloon catheter tip, in an attempt to limit perforation (Fig. 5). Once advancement had been made, the balloon was deflated and advanced over the laser catheter. The process was then repeated with laser catheter advancement, by use of the guidance of the adjacent balloon. After the occluded arterial segment was completely penetrated, a guide wire was used to
Excimer laserfemoral angioplasty 609
Fig. 2. This previously stenotic artery, seen in Fig. 1, was first traversed with a 0.018 guide wire and then a 2.2 mm over-the-wire laser catheter. The resulting lumen is sufficient to allow standard balloon angioplasty.
position a standard balloon angioplasty catheter for luminal enlargement (Fig. 6). Permanent radiographic hard copy of each step was procured, and at the termination of the procedure all introducer sheaths were removed. Heparin was not reversed after any procedure. The number of 200 nsec pulses was recorded and ranged from 540 to 9200 (mean, 3083). At a usual pulse rate of 30 Hz, this represents an actual laser on-time of 18 to 306 seconds. Patients were pretreated with 325 mg aspirin and maintained on aspirin, 325 mg daily, indefinitely. Only those with thrombotic complications were given heparin in the postprocedure period, and these patients were then converted to sodium warfarin (Coumadin) therapy if appropriate to maintain a prothrombin time 1.5 times control. Patients were
610 McCarthy et al.
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Fig. 3. This previously stenotic artery, seen in Figs. I and 2, now has a significantly improved lumen after laser angioplasty and standard balloon angioplasty.
Fig. 4. Superficial femoral artery occlusion of a patient with foot gangrene.
evaluated with Doppler ankle/brachial index measurements in the immediate postprocedure period, after 24 hours, 2 weeks, 4 weeks, 3 months, 6 months, and will be studied each year. Initial success was defined as an anatomically patent vessel with corresponding ankle/brachial index rise of at least 0.15 or an appropriate change in arterial wave for patients with calcified vessels.
no failures, and long lesions ( > 10 cm) were successfully treated in only two (22%) with nine failures (Table I). Technical success could be further subcategorized by success in 11 of 21 total arterial occlusions and success in four of five stenotic lesions. The ability to pass a guide wire was a predictor of success, with 13 of 19 (68%) successful. This compared to only two of seven (29%) primary successes where an end-on, balloon-guided catheter was used for totally occluded vessels. The reasons for procedure failure are illuminating. Perforation occurred in six individuals, and of those, three developed arteriovenous fistulas with angiographic confirmation. In one patient because of distal embolization the procedure had to be terminated. In four patients the procedure was initially successful, but even after balloon angioplasty, the vessel immediately thrombosed. O f the 11 initial
RESULTS The effectiveness of this procedure is best demonstrated by defining the technical success rate with early patency and evaluating the patency of that subgroup. Initial technical success was achieved in 15 (58%) of the 26 lesions treated. Short lesions ( = 5 cm) were effectively opened in 10 (83%), with two failures. Medium-length lesions ( > 5 to 10 cm) were successfully opened in three cases (100%) with
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F~cimer laserfemoral angioplasty 611
Fig. 5. This occluded artery, seen in Fig. 4, was primarily opened with a balloon-oriented end-on catheter. The lumen was not sufficient but allowed standard balloon angioplasty.
Fig. 6. After balloon angioplasty, this previously occluded artery, seen in Figs. 4 and 5, had a diameter resembling the adjacent vessel.
technical failures, five patients elected to live with their claudication and were discharged from the hospital. Five individuals went on to femoral popliteal bypass to relieve claudication, and one of these required operation on an emergency basis the same day as laser angioplasty. This patient had increasing leg ischemia resulting from embolic occlusion of the below-knee popliteal artery. The embolus was removed at the time of bypass. One patient was deemed too medically unstable for operative intervention with bypass and after a period of stabilization underwent elective above-knee amputation. During the early follow-up to 14 months after technical success, 8 of 15 initially successful procedures failed (53%). These failures occurred between 10 days and 6 months after the initial procedure (mean, 3.2 months). In this group of eight, three had
elective femoral popliteal bypass with success. One elected no surgical intervention, and one underwent a successful atherectomy procedure with a rotary device, which is functioning 8 months after its completion. One patient who had bilateral procedures, both of which failed, was an elderly bedridden, patient on dialysis who had been previously deemed too ill to undergo surgical bypass. This patient eventually underwent bilateral below-the-knee amputations. Early patency has been achieved in 7 of the initial 15 successful cases (47%), with a mean follow-up of 9.5 months (1.5 to 14 months). Initial change in ankle/brachial index for the 15 initial successes documented a mean increase of 0.34 from 0.49 to 0.83. Two patients who had uncompressible tibial vessels were excluded from these calculations.
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612 McCarthy et al.
Table I. Initial technical success and failure Lesion Catheter length Immediate (cm) Over-the-wire Balloon-centered patency
Occlusion Short
MediLlnq
Long
Stenoses Short Medium
Long
1.0 1.2 2.5 3.0 3.2 4.0 4.0 4.0 4.4 4.5
X X X X X
X X
Yes Yes Yes Yes No Yes Yes Yes No Yes
5.1 8.7
X X
Yes Yes
11.5 13.5 14.0 15.5 17.0 17.5 17.5 18.0 30.0
X X
X X
Yes No No No No No No No No
3.5 5.0
X X
Yes Yes
7.5
X
Yes
20.0 27.0
X X
Yes No
X X X
X X X X X
Management of complications Although three of 26 limbs were lost to one above-knee and two below-knee amputations, none of these were unanticipated. All patients had been deemed too ill for surgical bypass should a percutaneous technique prove ineffective. Thus no limb loss was attributed to a worsened condition resulting from the laser angioplasty. Arterial perforation in the distal superficial femoral artery was observed in six cases, all of which resolved spontaneously without operative intervention. Three arteriovenous fistulas occurred as a result of these perforations, and they also resolved, as evidenced by follow-up angiograplay, without any intervention within i hour of their occurrence. Definite macroembolization to the popliteal level occurred in three patients. One resuited in treatment failure and a prearranged limb amputation. Another required emergency femoral popliteal bypass with embolectomy, and the third was successfully treated with urokinase therapy. Groin hematoma formation was evident in six patients, two of whom required operative intervention and arterial repair with local anesthesia. Four
other hematomas were minor and resolved without surgery. Distal superficial femoral and popliteal artery thrombosis developed in one patient during the procedure and was successfully treated with urokinase therapy. This patient remains in the early patency group.
DISCUSSION The initial success and early patency of patients treated with a 308 nm excimer laser and accompanying balloon angioplasty is disappointing. Only 15 of 26 patients had technical success. The length of arterial stenosis or occlusion correlated closely with the initial technical patency, and only two of nine (22%) lesions longer than 10 cm were successfully treated. This corresponds with success in 33% of lesions longer than 15 cm in recent work by Litvack et al.,~o who recorded the only other series of peripheral artery excimer laser angioplasty. In this series eight lesions were longer than 15 cm, only one of which was successfully opened. Long superficial femoral artery stenosis remains a challenge for percutaneous angioplasty, even if initial success is achieved. Murray et al." found a dismal 33.1% 6-month patency if lesions treated with balloon angioplasty alone were greater than 7 cm in length. ~1 In comparison, 6-month patencies of 93.7% were reported for shorter lesions. The initial technical success rate of 57% in the current study is lower than that of Litvack et al.,o (77%) but better than many other laser angioplasty reviews. Patient selection appears critical to define initial technical success rates. After gaining some experience in the Northwestern study, we avoided extremely long stenoses or occlusions, and initial technical results improved. Perforations of the artery had a profound impact on the technical success of this procedure. Six patients, 23% of the study group, experienced this difficulty, and each perforation required termination of the procedure. This rate is similar to the experience of Seeger et al?2 with 22% perforation in 10 of 46 arteries, using a heated tip sapphire lens instrument. Every perforation occurred in the lower superficial femoral artery at the adductor hiatus. Although three resulted in obvious arteriovenous fistulas, all six perforations proved completely benign and resolved without any operative intervention. Nevertheless, once perforation occurred, the chance of a successful recanalization was lost. Perforations occurred with the balloon-centered catheter five times and only once when an over-the-wire assembly was used. The propensity of the current system to perforate reflects the stiffness of the fiber and lack of any real tip
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guidance. In this series the balloon-centered catheter was used seven times, with only two successes. However, in many cases these catheters opened an extended length of artery before finally being found outside the arterial lumen. Thus the problem is not an inability to penetrate occluded arterial tissue but rather guidance, and guidance may be the real limit of initial success with this laser. There was never any difficulty advancing the catheter in any of the 26 cases. The laser fiber could be passed with manual pressure and advanced with almost no tactile resistance even when radiographic calcified arteries were present. This is contrary to the experience with some existing laser units where lengthy exposure time is necessary for tissue ablation. Actual laser energy application time averaged 103 seconds (18 to 306 sec), and once the catheter was positioned this usually required 10 or 15 minutes of actual manipulation. Catheter-tip guidance has been addressed in other systems by measuring reflected radiation from a laser beam to differentiate diseased tissue from normal arterial wall. This concept seems conceptually sound but has been hard to apply clinically. ~s Other guidance systems are necessary, and external or intraluminal ultrasonic systems have been proposed. ~4 Early patency was seen in only 47% of the 15 patients in whom immediate technical success had been possible, with a mean follow-up of 9.5 months. This is less than the 71% reported by Litvack et al) ° with excimer lasers, also using a 9-month interval. The reason for this difference is uncertain in that the patient mix of Litvack et al. of stenoses and length of occlusions was similar to the present study. These patency rates are distinctly less than any reported surgical bypass at the femoropopliteal level. Complete arterial occlusions seemed most amenable to long-term success in the present study. Eleven of 15 initially successful lesions were complete occlusions, and seven (64%) of those remained patent at 9.5 months. Four of the initial technical successes were in vessels with stenoses, and none of that group remained patent at most recent follow-up. Five of the seven long-term successes are characterized by initial short occlusions with near-normal inflow and runoff patency. Two, however, represent successes in severely diseased arteries with runoff into blind popliteal segments. All occlusions developed in the first 6 months with a mean occlusion time of 3.2 months. This is similar to the pattern of early failure and then stability reported for long-term followup in coronary balloon angioplasty by Gruentzig et al. 2 where patency at 6 months after balloon
Excimer laserfemoral angioplayty 613
angioplasty heralded a good possibility of much longer patency. Although other laser wavelengths are capable of atherosclerotic ablation, excimer lasers may offer potentially greater clinical application, ls'16 Excimer lasers disobliterate even calcified plaque without creating significant thermal accumulation. 8"17Mechanistically, ablation is thought to be photochemical rather than thermal and allows excision of diseased tissue to take place at near ambient temperatures. The advantage of this characteristic has been used in ophthalmology for corneal surgery) 8 Application of excimer lasers to cardiovascular tissue was demonstrated by Isner et al. ~9 with the examination of excised coronary artery and cardiac valve tissue. Their study demonstrated a lack of coagulation necrosis as compared to thermal laser tissue interaction. This same group investigated ex vivo transmission of excimer energy through silica optical fibers to disobliterate atherosclerotic arteries and to interact in a fluid field. 2°'21 The observed low temperature cutting of excimer lasers initiated the theory of photochemical breaking of molecular bonds rather than the usual thermal degradation of tissue. However, some interesting speculation exists that the process may be thermally related. Clarke et al. 22 studied argon fluoride (193 nm) and xenon fluoride (131 nm) excimer lasers that were directed at samples of myocardium and atherosclerotic coronary artery segments. They used gas chromatography to evaluate degradation byproducts, and a series of short chain hydrocarbons were identified that are byproducts similar to those produced by flame-torching of similar tissue. This indirect evidence of at least a microscopic thermal mechanism is of interest. Steg et al.6 have compared contraction of vascular smooth muscle exposed to continuous-wave laser irradiation and excimer laser exposure. They conclude that excimer radiation does not cause the contraction of smooth muscle seen with other lasers but rather induces a "relaxation response." In the current series arterial spasm after laser fiber passage was not encountered. This advantage may be important in treating small vessels such as coronary and tibial arterial applications where transient spasm could cause procedural failure. In the present study despite the ability of the excimer laser to traverse all occluded arteries, a lumen diameter sufficient to be left without balloon angioplasty was not achieved. Therefore balloon angioplasty was used in every case to increase lumen diameter. This makes assessment of the excimer laser effect difficult. Given the lack of tissue heating, the
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core of the atheroma removed by the laser is comparable to a direct incision. Thus once a balloon angioplasty has taken place, the final luminal surface remains little influenced by the excimer laser. Extended patency then is as much a test of balloon angioplasty as it is of excimer laser energy. To truly evaluate this technology, catheters large enough to create lumens not requiring balloon angioplasty must be developed and tested. Angioplasty by use of balloon-assisted excimer laser is possible with immediate and early results dependent on the existing arterial pathology. Long stenoses and occlusions are uniformly unsuccessful when treated by this technique. In comparison, short arterial occlusions, even those accompanied by significant calcification, can be penetrated by the excimer laser and successfully dilated with balloon angioplasty. Therefore even in its primitive form, this laser provides potential above and beyond primary balloon angioplasty. However, the rates of both initial technical success and early patency are much lower than those of treatment with arterial bypass. Full evaluation awaits the development of larger laser catheters with some form of guidance to prevent arterial perforation. REFERENCES 1. Dotter CT, Judkius MP. Transluminal treatment of arteriosclerotic obstruction: description of a new technique and a preliminary report of its application. Circulation 1964;30: 654-70. 2. Gruentzig AR, King SP, Schlumph M, Siegenthaler W. Long-term follow-up after percutaneous transluminal coronary angioplasty: the early Zurich experience. N Engl J Med 1987;316:1127-32. 3. Nordstrom LA, Castaneda-Zuniga WR, Young EG, Von Seggern KB. Direct argon laser exposure for recanalization of peripheral arteries: early results. Radiology 1988;168:35964. 4. Michaels JA, Cross FW, Shaw P, et al. Laser angioplasty with a pulsed NdYAG laser: early clinical experience. Br J Surg 1989;76:921-4. 5. Vorwerk D, Zolotas G, Hessel S, Adam G, Guenther RW. Vascular tissue ablation by an Erbium-YAG laser: a fibertransmittable pulsed laser in the infrared range. Invest Radiol 1990;25:235-9. 6. Steg PG, Rongione AJ, Gal D, DeJesus ST, Clarke RH, Isner JM. Pulsed ultraviolet laser irradiation produces endotheliumindependent relaxation of vascular smooth muscle. Circulation 1989;79:189-97.
7. Haina D, Landthaler M. Fundamentals of laser light interaction with human tissue, especially in the cardiovascular system. Thorac Cardiovasc Surg 1988;36:118-25. 8. Cross FW, Bowker TJ. The physical properties of tissue ablation with excimer lasers. Med Instrumentation 1987;21: 226-30. 9. Wollenek G, Laufer G, Grabenwoger F. Percutaneous transluminal excimer laser angioplasty in total peripheral artery occlusion in man. Lasers Surg Med 1988;8:464-8. 10. Litvack F, Grundfest WS, Adler L, et al. Percutaneous excimer laser and excimer laser-assisted angioplasty of the lower extremities: results of initial clinical trial. Radiology 1989; 172:331-5. 11. Murray RR Jr, Hewes RC, White RI Jr, et al. Long-segment femoropopliteal stenoses: is angioplasty a boon or a bust? Radiology 1987;162:473-6. 12. Seeger JM, Abela GS, Silverman SH, Jablonski SK. Initial results of laser recanalization in lower extremity arterial reconstruction. J VAsc SURG 1989;9:10-7. 13. Laufer G, WoUenek G, Hohla K, et al. Excimer laser-induced simultaneous ablation and spectral identification of normal and atherosclerotic arterial tissue layers. Circulation 1988;78: 1031-9. 14. Yock PG, Linker DT. Intravascular ultrasound: looking below the surface of vascular disease. Circulation 1990;81:1715-8. 15. Isner JM, Rosenfield K, Losordo DW. Excimer laser atherectomy: the greening of Sisyphus. Circulation 1990;81: 2018-21. 16. Sartori M, Henry PD, Sauerbrey R, Tittel FK, Weilbaecher D, Roberts R. Tissue interactions and measurement of ablation rates with ultraviolet and visible lasers in canine and human arteries. Lasers Surg Med 1987;7:300-6. 17. Duda SH, Karsch KR, Haase KK, Huppert PE, Claussen CD. Laser ring catheters in excimer laser angioplasty. Radiology 1990; 175: 269- 70. 18. Seiler T, Bende T, Woilensak J, Trokel S. Excimer laser keratectomy for correction of astigmatism. Am J Ophthalmol 1988;105:117-24. 19. Isner JM, Donaldson RF, Deckelbaum LI, et al. The excimer laser: gross, light microscopic and ultrastructural analysis of potential advantages for use in laser therapy of cardiovascular disease. J Am Coil Cardiol 1985;6:1102-9. 20. Isner JM, Gal D, Steg PG, et al. Percutaneous, in vivo excimer laser angioplasty: results in two experimental animal models. Lasers Surg Med 1988;8:223-32. 21. Isner JM, DeJesus SR, Clarke RH, Gal D, Rongione AJ, Donaldson RF. Mechanism of laser ablation in an absorbing fluid field. Lasers Surg Med 1988;8:543-54. 22. Clarke RH, Isner JM, Donaldson RF, Jones G II. Gas chromatographic-light microscopic correlative analysis of excimer laser photoablation of cardiovascular tissues: evidence for a thermal mechanism. Circ Res 1987;60:429-37.
Submitted Oct. 9, 1990; accepted Oct. 19, 1990.
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