ULTRASOUND-GUIDED STENT PLACEMENT

INTRAVASCULAR IMAGING AND DOPPLER

0733-8651/97 $0.00

+ .20

ULTRASOUND-GUIDED STENT PLACEMENT Robert J. Russo, MD, PhD

During the last 5 years, there has been a marked improvement in the quality of intravascular ultrasound (MJS) images (Fig. 1). At the same time, ultrasound imaging catheter design and performance have been greatly enhanced. As a result, the indications for NUS have expanded and presently include diagnostic imaging as well as IWS-guided interventional therapy. N U S has been used to assess the results of and direct balloon angioplasty, directional coronary atherectomy, rotational atherectomy, and stent placement. There are many opinions, however, concerning the requirement for M J S in a laboratory fierforming coronary interventions. This lack of consensus most likely arises from the paucity of randomized data on acute procedural results and long-term patient outcome. This article examines the role of M J S in coronary stent placement and reviews the available data from NUS-guided stent placement clinical trials completed and in progress.

result by conventional angiography.l6< 25 Subsequently, ultrasound was used to assess the results of coronary stent placement and direct further therapy.l0 Given the intense echogenicity of metallic stents and the circumferential mode of deployment, intravascular imaging appeared to be an ideal method for assessing the results of stent placement.64Early investigators also noted the poor correlation of angiographic and ultrasound dimensions. After stent placement, a significant improvement in lumen diameter was noted by quantitative coronary angiography. Considerably less improvement in lumen size, however, was found by ultrasound assessment, suggesting that angiography overestimates lumen dimensions and thus the adequacy of stent placement in vein grafts and native coronary 30, 38, 42 Coronary angiography has arte~ies.~, been the gold standard for guiding and assessing the results of stent implantation. With greater sensitivity than angiography and little interobserver or intraobserver variability, however, I W S may emerge as the preferred method for evaluating the acute and longterm results of coronary stent placement.33

INITIAL EXPERIENCE

Early investigators used M J S as an adjunct to angiography to assess the results of balloon angioplasty. A significant postprocedure residual stenosis detected by I W S prompted coronary stent placement despite an adequate

PRE-STENT PLACEMENT INTRAVASCULAR ULTRASOUND

The availability of smaller catheters (2.9, 3.2, and 3.5 F) has made pre-stent placement

From the Division of Cardiovascular Diseases, Scripps Clinic and Research Foundation, La Jolla, California

CARDIOLOGY CLINICS VOLUME 15 NUMBER 1 FEBRUARY 1997

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Figure 1. A, lntravascular ultrasound image of a saphenous vein bypass graft representative of images from 1991. B, Images of a left main coronary artery from 1996. A marked improvement is noted in resolution, far-field penetration, and definition of plaque morphology.

I W S feasible for many patients. Two laboratories have documented the impact of preintervention I W S on clinical decision making. In one series, preintervention imaging was performed in 313 nonconsecutive target lesions. On the basis of additional information provided by IWS, there was a change in planned therapy in 40% of lesions. This included detection of an angiographically occult significant stenosis in 6% of lesions, angiographic overestimation of lesion severity in 7%, and assessment of lesion composition leading to a change in strategy or device selection in 26%. In this study, dissections, true aneurysms, and fibrotic vein graft lesions were treated with stent placement, and significant superficial calcium was treated with rotational atherectomy, with or without subsequent stent placement, when directed by I W S findings.34 In a second series, 100 nonconsecutive lesions were assessed before intervention. Information provided by IVUS and not detected by angiography led to a specific clinical decision or a change in planned therapy in 74% of lesions. In this series, an angiographically occult stenosis, dissection, or inadequate percutaneous transluminal coronary angioplasty (PTCA) result (a total of 43%) detected by ultrasound was treated with stent placem e ~ ~The t . ~patients ~ who underwent IVUS analysis in both series were enrolled in a nonconsecutive manner and were selected for imaging because of inconclusive angiographic findings. A randomized trial is necessary to determine the frequency with which ultra-

sound influences pre-stent placement treatment strategies. Preintervention I W S may also be used as an adjunct to angiography before stent placement to provide additional information on lesion length (with automated motorized pullback), reference vessel diameter, and the presence of target lesion calcium (both superficial and deep). STENTING WITHOUT ANTICOAGULATION

Coronary stents have been shown to be effective for the treatment of abrupt coronary closure,17,45 suboptimal angioplasty result^,^, 14, 23 and reduction of resten~sis.'~, 28, 53 These benefits have been weighed against the low but finite risk of stent thrombosis,2. 41, 51, 61 a potential catastrophic event complicating stent placement. To decrease the incidence of stent thrombosis, an aggressive anticoagulation regimen including warfarin and heparin was adopted by early investigators. This approach, however, was associated with prolonged hospitalization and significant morbidity, most commonly, bleeding complications at the femoral access site.I3,53 Milan Experience Colombo and associatess used IVUS to guide stent placement and subsequently discharged patients from the hospital without warfarin anticoagulation. The goal of this trial

ULTRASOUND-GUIDED STENT PLACEMENT

was to reduce bleeding complications associated with prolonged systemic anticoagulation after coronary stent placement by withholding postprocedure warfarin. Initial studies of M J S imaging after Palmaz-Schatz stent placement revealed that 80% to 87% of stents were insufficiently dilated when compared to reference vessel dimensions despite maximum inflation pressures of 11 to 12 atm and 40 These a successful result by angi~graphy.'~, early observations suggested that stent thrombosis may be caused, in part, by incomplete stent expansion rather than the inherent thrombogenicity of a metallic stent. Criteria for study entry in this initial trial of ultrasound-guided stent placement without warfarin anticoagulation included evidence of single or multiple vessel coronary disease with a target lesion stenosis of 70% or greater by visual estimate of angiography. Exclusion criteria included vessels less than 2.5 mm by visual estimate and those with diffuse distal disease (which might compromise outflow after stent placement). Patients were not excluded on the basis of the indication for stent implantation, lesion location, complex lesion morphology, or vessel type. During the stent implantation procedure, angiographic optimization was performed to achieve an acceptable result with less than 20% residual stenosis by visual estimate. After an acceptable angiographic result was obtained, at a point when the procedure would ordinarily be terminated, I W S was performed, and subsequent treatment decisions were based on IVUS findings. The rationale for ultrasound-guided stent placement was that high-pressure balloon inflations (15 2 3 atm) guided by M J S would result in optimal stent expansion, complete apposition, and a marked decrease in the incidence of stent thrombosis. Patients who fulfilled ultrasound criteria for optimal stent expansion (see later) were discharged from the hospital on ticlopidine (500 mg/day for 1 to 2 months) and aspirin (325 mg/day) or aspirin alone. By withdrawing warfarin anticoagulation, a marked decrease was anticipated in hospital length of stay and bleeding complications. A total of 359 consecutive patients with 452 lesions underwent Palmaz or Palmaz-Schatz stent placement. After high-pressure balloon inflations, 70% of stents required further balloon inflations to fulfill ultrasound criteria for optimal expansion despite an adequate angiographic result (<20% residual stenosis). \

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With increased experience and a change in the criteria for success by IVUS, the incidence of incomplete stent expansion after high-pressure inflations decreased from 88% in the first third of lesions to 40% in the last third. In those patients requiring additional balloon inflations after the initial I W S evaluation, an increase of 0.5 mm (by IWS) in diameter and 35% in cross-sectional area was noted. Oversized and appropriate-sized final balloon inflation strategies were used sequentially during this trial. The use of larger balloons in the oversized strategy was reflected by a balloon-to-vessel ratio (measured mediato-media in the proximal reference vessel) of 1.20 compared to 1.05 when appropriatesized balloons were used for final stent expansion. When the oversized balloon strategy was used, an improvement in final lumen diameter and residual stent stenosis was noted when compared to the appropriatesized strategy (3.44 versus 3.21 mm and -9 versus + YO). The more aggressive approach, however, resulted in a procedure complication rate of 5.7%, which fell to 1.0% when appropriate-sized balloons were used. Overall a significant complication occurred in 1.7% of patients as a result of further therapy directed by I W S findings. At 2-month clinical follow-up (which included intraprocedural, in-hospital and early postdischarge events) after IVUS-guided placement, the rate of stent thrombosis was 0.9%. This represented a significant improvement compared to STRESS (Stent Restenosis Study) and BENESTENT (Belgian Netherlands Stent Study) clinical trial^.'^, 53 At 6-month clinical follow-up, 13.1% of patients required repeat angioplasty for symptomatic restenosis. On the basis of the results of this study, it was concluded that a low rate of stent thrombosis could be achieved when the strategy of IVUS-guided high-pressure balloon inflation was used. In addition, warfarin could be withdrawn and patients discharged on antiplatelet therapy with a significant decrease in bleeding complications and length of hospitalization. As noted in many prior and subsequent studies, I W S was important in assessing adequate stent expansion, which was frequently overestimated by angiography. No-War Trial

In the Scripps Clinic No-War Trial (Ultrasound-Guided Coronary Stent Placement Without Warfarin Anticoagulation), the feasi-

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bility of elective Palmaz-Schatz coronary stent placement without warfarin anticoagulation after an optimal result as determined by I W S was assessed.47,48 Patients who met specific clinical, angiographic, and I W S criteria were discharged from the hospital on a regimen of reduced anticoagulation that included aspirin (325 mg/day) and ticlopidine (500 mg/day). Patients who failed to meet clinical, angiographic, or IVUS criteria received warfarin before discharge. To identify patients at low risk of stent thrombosis for study entry, the following inclusion criteria for discharge without warfarin were used: elective stent placement in a native vessel, saphenous vein graft or left internal mammary artery graft, single or multiple stent placement in one or two vessels, and a distal reference vessel 2.5 mm or greater in diameter by visual estimate of angiography. To identify patients at high risk of stent thrombosis, the following exclusion criteria were used: angiographic evidence of intraluminal thrombus, TIM1 (Thrombolysis in Myocardial Infarction) flow less than grade 3 after stent placement, dissection at stent margins not covered by a subsequent stent, stent placement for chronic total occlusion, stent placement in the sole remaining circulation or left main equivalent, myocardial infarction within 5 days, and clinical requirement for warfarin anticoagulation not related to stent implantation. After stent delivery, a diligent attempt was made to optimize stent lumen dimensions using balloon catheters inflated to 16 atm or more of pressure. When an optimal angiographic result was obtained ( 4 0 % residual stenosis), I W S was used to assess the result of stent placement. After initial ultrasound evaluation, 38% (48/125) of patients fulfilling angiographic criteria (
stent restenosis (in a mixed population including restenotic and long lesions in vein grafts and native coronary arteries). Vascular complications were less frequent in patients discharged without warfarin (2.7% versus 13.2’/0), and hospital length of stay was shorter (1.9 versus 5.4 days). Thus, the No-War Trial demonstrated that elective IVUS-guided stent placement without warfarin anticoagulation decreased vascular complications and length of stay without increasing the incidence of stent thrombosis. MUSIC Trial

The MUSIC trial (Multicenter Ultrasound Stenting In Coronaries) is a multicenter, prospective, nonrandomized trial of stent placement without warfarin. The primary objective of the trial is to assess the safety and efficacy of IVUS-guided optimal stent expansion in de novo lesions after placement of a single spiral articulated Palmaz-Schatz coronary stent. Patients fulfilling IVUS criteria for optimal stent expansion (see later) are discharged on a reduced dose of aspirin (2100 mg/day) without warfarin anticoagulation. Patients not meeting ultrasound criteria for optimal stent deployment receive standard anticoagulation. Primary endpoints of the MUSIC study are safety, as defined by clinical events including death, myocardial infarction, coronary artery bypass surgery, and repeat PTCA within 30 days, and incidence of angiographically documented stent thrombosis and bleeding complication within 30 days. Secondary endpoints include the incidence of angiographic restenosis (250% stenosis) at 6 months, longterm clinical outcome at 6 months including the need for target lesion revascularization, and a correlation of IVUS findings and quantitative coronary angiography to determine the value and requirement of ultrasound during coronary stent placement. At 6 months of follow-up, interim results of 161 patients discharged without warfarin, 27 of whom did not fulfill NUS criteria on retrospective core laboratory analysis, showed the incidence of stent thrombosis was 0.6% and the rate of target lesion revascularization was 4%” (P deJaegere: personal communication). INTRAVASCULAR ULTRASOUND CRITERIA FOR OPTIMAL STENT PLACEMENT

Early ultrasound criteria for optimal stent placement were criticized for being arbitrary

ULTRASOUND-GUIDEDSTENT PLACEMENT

Figure 2. A-D, A single Palmaz-Schatz (PS1530) coronary stent was placed in the proximal portion of the posterior descending coronary artery and postdilated with a 2.75-mm balloon at 18 atm with an adequate angiographic result (
Figure 3. A, A 4.0-mm Palmaz stent (P104) was placed in the ostium of a dominant right coronary artery and postdilated with a 4.0-mm balloon at 18 atm. An adequate angiographic result was obtained (
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Figure 4. A, A single Palmaz-Schatz (PS1530) coronary stent was placed in the midportion of a right coronary artery with an excellent angiographic result. 13,Although intravascular ultrasound imaging showed adequate stent expansion and apposition, a significant dissection was noted in the proximal reference vessel, which exposed the medial layer and required placement of an additional stent. IVUS = lntravascular ultrasound.

and cumbersome. Subsequently, criteria (AVID [AngiographyVersus Intravascular ultrasound-Directed stent placement] and MUSIC) were established to address the three fundamentals of stent placement: (1) adequate expansion compared to the distal reference vessel (or combination of proximal and distal reference vessels) such that the stent does not create nonlaminar coronary flow (Fig. 2); (2) full apposition of stent to vessel wall to avoid turbulent flow through the stent struts, which may contribute to excessive thrombus deposition (Fig. 3); and (3) absence

of significant (angiographically occult) dissection that exposes the deep elements of a vein graft wall or media of a native vessel (Fig. 4), which are thought to be highly thrombogenic. Stent geometry or eccentricity (minor axis/ major axis) have not been shown to change significantly or improve with further highpressure balloon inflations or to increase significantly nonlaminar coronary flow. In addition, some investigators have suggested a sliding scale to evaluate adequate stent expansion, requiring an in-stent minimal luminal area of 100% or greater compared to

Table 1. A COMPARISON OF INTRAVASCULAR ULTRASOUND CRITERIA FOR OPTIMAL STENT PLACEMENT Study or Trial

Vessels Treated

Colombo et ale

N

+ SVG

No-War4’. AVID4’, 50 MUSIC”

N N

+ SVG + SVG

RAVES”,

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N

63

SVG

Expansion of MLA

260% of (PRV

+

DRV vessel CSA)/2; altered to z100% DRV lumen CSA 290% of DRV lumen CSA 290% of DRV lumen CSA 290% of (PRV + DRV lumen CSA)/2 and 2100% CSA of the smaller reference lumen 290% Of (PRV + DRV lumen)M

Dissection

Apposition

Other

-

Yes

Yes Yes

-

Yes Yes Yes

Symmetry index >0.7

-

Yes

Symmetry index >0.7

No adjacent lesion >6O% CSA; symmetry index >0.7*

-

\

MLA = Minimal luminal area within the stent; PRV = proximal reference vessel; DRV = distal reference vessel: CSA = crosssectional area; Symmetry index = minimal lumen diameterhnaximal lumen diameter; SVG = saphenous vein grafts; N = native vessels. ‘Used in the initial portion of the study and then abandoned after it was shown not to change significantly during stent optimization.

ULTRASOUND-GUIDED STENT PLACEMENT

the distal reference lumen for smaller vessels (<2.5 mm) and 70% to 80% or greater for larger vessels (>3.5 to 4.0 mm). Validation studies are in progress. Although ultrasound criteria (Table 1) for optimal stent expansion are based on the above-mentioned principles of coronary stent placement, to date, no randomized study of IVUS-guided versus angiography-guided stent placement has demonstrated a significant difference in the incidence of stent thrombosis when the two techniques are compared. Studies comparing the incidence of target lesion revascularization are in progress (AVID and OPTICUS [Optimization with Intracoronary Ultrasound to Reduce Stent Resten~sis]).~ INTRAVASCULAR ULTRASOUND-GUIDED STENT PLACEMENT

Many additional investigators have demonstrated the use of I W S during stent deployment. During the early phase of PalmazSchatz stent placement, it was noted with ultrasound imaging that most stents were suboptimally deployed after placement with the stent delivery system balloon and that stent expansion improved after high-pressure inflations with a noncompliant balloon catheter.26When the strategy of high-pressure balloon inflatioh guided by I W S was applied to a patient cohort similar to those enrolled in a significant decrease the BENESTENT was noted in the rate of stent thrombosis within 1 month and restenosis at 6 month^.^ I W S was used to guide stent implantation in a randomized comparison of hospital discharge for patients taking ticlopidine and aspirin versus aspirin alone.22In this study, IVUS criteria for optimal stent expansion included achievement of a stent minimal cross-sectional area 80% or greater of the distal reference lumen cross-sectional area. In smaller vess,els (C7.5 mm2area), criteria were modified to a stent lumen cross-sectional area 100% or greater of the distal reference lumen to decrease the risk of partial outflow obstruction. Also, IVUS has been used to direct highpressure balloon inflations after stent delivery when 6 F guiding catheters are used via a percutaneous transradial approach.27 I W S has been used to guide stent placement after angioplasty complicated by dissection. Because a coronary guide wire may enter a false lumen when reintroduced following severe vessel dissection, IVUS has

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been used to detect the true arterial lumen and direct stent placement in the true rather than false lumen.29Other studies report the use of IVUS to define a low-risk group and guide stent placement for coronary dissection without postprocedural systemic anticoagulation.4,52 STENT PLACEMENT WITHOUT INTRAVASCULAR ULTRASOUND

The ability to optimize stent placement with IVUS-guided high-pressure balloon inflations led to the hypothesis that an optimally placed stent would not require warfarin anticoagulation. Subsequently, post-stent placement warfarin anticoagulation was withheld in patients fulfilling ultrasound criteria for optimal stent deployment, resulting in a low.incidence of stent thrombosis.* Other investigators who adopted the strategy of post-stent deployment high-pressure dilation reported similar stent thrombosis rates with20, 37, 46 Although acute out IVUS g~idance.~, clinical results were similar, however, it was not known if angiography-guided stent deployment would result in late outcomes and restenosis rates similar to IVUS-guided stent deployment. ANGIOGRAPHY VERSUS INTRAVASCULAR ULTRASOUND TRIALS AVID

In AVID, a multicenter, randomized trial, patient outcome after IVUS-directed stent placement is compared to stent placement directed by angiography alone. Inclusion criteria for study entry are elective placement of single or multiple stents in a vein graft, internal mammary artery graft, or native vessel with a reference vessel 2.5 mm or greater by visual estimate of angiography . Exclusion criteria are similar to those used in the NoWar study. Target enrollment in the AVID study is 800 patients with clinical follow-up. After an optimal angiographic result is obtained (
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dissection is detected. In the ultrasound-directed group, patients who fulfill IVUS criteria (see Table 1) are discharged on aspirin and ticlopidine. Patients who fail ultrasound criteria on initial evaluation are treated with larger balloons or placement of additional stents in an attempt to meet previously established criteria for apposition, lack of dissection, and residual stenosis. Endpoints for the AVID study include acute stent dimensions, short-term clinical events including stent thrombosis within 30 days, and target lesion revascularization at 6 and 12 months. Interim results have been reported on 270 patient^.^^,^^ In the angiography group, 2.6% of patients crossed over to further therapy because of a significant dissection detected by IVUS. In the ultrasound group, 33% of patients required additional therapy to fulfill IVUS criteria, although an adequate angiographic result had been obtained. For those patients in the ultrasound group who underwent further therapy, an increase in luminal diameter of 0.59 mm and an increase in cross-sectional area of 32% were noted. No patient experienced a complication as a result of further therapy directed by ultrasound findings. Although all patients in the angiography group fulfilled angiographic criteria for optimal stent placement (loo/, residual stenosis by visual estimate), 29% failed to meet ultrasound criteria for complete expansion (290% of the distal reference vessel lumen crosssectional area) when core laboratory analysis was performed. This comparison underscores the relative insensitivity of angiography in evaluating lumen dimensions after stent placement when compared to IVUS.49,50 At 30-day follow-up, 1.8% of patients in the angiography group and 1.9% in the ultrasound group experienced acute in-hosp'ital stent thrombosis. The incidence of myocardial infarction, repeat angioplasty, bypass surgery, and death at 30 days was similar in both groups. Thus, to date, IVUS-directed stent implantation has improved acute stent dimensions without an increase in complications but has not influenced the 30-day clinical event rate. Assessment of the major clinical endpoint of the AVID study, target lesion revascularization or in-stent restenosis at 6 and 12 months, is pending. OPTICUS

The OPTICUS study is a multicenter, randomized trial scheduled to begin enrollment

in late 1996. This study will test the hypothesis that IVUS guidance during stent deployment may decrease the rate of target lesion revascularization at 6 months. It will prospectively compare ultrasound-guided versus angiography-guided stent placement restenosis rates. In this study, one or two 8-, 14-, or 18mm Palmaz-Schatz stents will be deployed. Target enrollment in this study is 500 patients and will include angiographic and IVUS follow-up at 6 months. Ultrasound criteria for optimal stent placement in this study are complete apposition of the stent over its entire length, an in-stent luminal area of the proximal stent segment 90% or greater of the proximal reference lumen area, and a minimal in-stent luminal area of 90% or greater of the average reference lumen area or 100% of the lumen area of the reference segment with the lowest lumen area (a sliding scale has also been proposed for larger vessels) (H Mudra: personal communication). Primary endpoints for the OPTICUS study are angiographically determined percent diameter stenosis and stent minimal luminal diameter at 6 months. Secondary endpoints include stent thrombosis, angiographically defined procedure success rate, bleeding complications, and procedure cost. It is anticipated that these two large-scale, multicenter, randomized studies (AVID and OPTICUS) will determine the value and establish the appropriate role of IVUS-directed coronary stent placement. OTHER INTRAVASCULAR ULTRASOUND STENT TRIALS STRUT

The STRUT (Stent Treatment Region assessed by Ultrasound Tomography) registry is a multicenter, prospective, nonrandomized, observational study15,32 (P Fitzgerald: personal communication). In this study, IVUS is used to assess the results of stent implantation after high-pressure balloon inflations in a procedure guided by angiography alone. Preliminary results from the STRUT registry include a 14% incidence of incomplete stent apposition and an 18% incidence of stent margin superficial dissection, or pockef flaps. Neither incomplete apposition nor angiographically occult stent margin flaps, however, were associated with an adverse outcome or an increase in the incidence of stent

ULTRASOUND-GUIDED STENT PLACEMENT

thrombosis. The rate of incomplete stent expansion after high-pressure balloon inflation was 48% when the stent was required to reach 90% of distal reference vessel lumen cross-sectional area. When the criteria were relaxed to 80% and 70% of the distal reference vessel lumen, the incidence of incomplete expansion was 18% and 6%. CRUISE

The CRUISE study (Can Routine Ultrasound Impact Stent Expansion) is a substudy of STARS (Stent Antithrombotic Regimen Study), a multicenter, prospective, randomized trial of reduced anticoagulation after Palmaz-Schatz coronary stent placement. CRUISE includes those patients enrolled in either the NUS-guided or NUS-documented portions of STARS. The purpose of CRUISE is to assess the impact of I W S on acute procedural outcome, 30-day clinical endpoints including stent thrombosis, and the rate of target lesion revascularization at 9 months. Enrollment in this study began in late 1995, and preliminary results are pending. OSTI

The purpose of the OSTI (Optimal STent Implptation) trial was to determine the relationship between implantation pressure and stent expansion. Sequential noncompliant balloon expansions were performed at 12, 15, and 18 atm with ultrasound assessment after each step. At 12 atm, 39% of stents placed were 90% or greater of the mean reference vessel (proximal + distal/2) cross-sectional area. At 15 and 18 atm, the number that fulfilled NUS criteria (290% of the mean reference vessel lumen cross-sectional area) rose to 42% and 659'0% (G Stone: personal communication). Further investigations are in progress using an expanded protocol. The relationship between stent implantation pressures and extent of expansion as assessed by IVUS has also been examined by other investigators? 24, 6o with similar results. POST

The POST (Predictors Of Stent Thrombosis) registry is a retrospective multicenter analysis

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of IVUS parameters that may be predictive of stent thrombosis. The difficulty in evaluating stent thrombosis in a prospective fashion is the low event rate (0.2% to 1.0%) with current techniques and antiplatelet medications. To collect 100 cases of stent thrombosis after an IWS-guided procedure in a prospective fashion would require a patient enrollment of prohibitive size (10,000 to 50,000). Case collection in the POST study began in mid-1996, and results are pending (P Yock: personal communication). RAVES

The RAVES (Reduced Anticoagulation in saphenous VEin graft Stent) trial is a multicenter study designed to evaluate the feasibility and safety of NUS-guided stent placement in vein grafts. Patients who fulfill ultrasound criteria for expansion, symmetry, and apposition (see Table 1) using adjunct high-pressure balloon dilatations are treated with reduced anticoagulation (specifically,aspirin and ticlopidine).62Using the strategy of IVUS-guided optimal stent expansion in a saphenous vein graft followed by reduced anticoagulation, there were no untoward clinical events including stent thrombosis in the early phase of the RAVES trial. Final results are pending. FUTURE DEVELOPMENTS IN INTRAVASCULAR ULTRASOUND

Several new applications of I W S during stent placement appear promising for the future. Combined IVUS-balloon catheters have been used for stent d e p l ~ y m e n t These . ~ ~ devices allow for ultrasound imaging during and after stent deployment to assess the results of stent placement without the need for catheter exchange. Imaging elements have also been placed within the central lumen of larger balloons to obtain IVUS images during stent d e p l ~ y m e n t . ~ ~ Interest in three-dimensional ultrasound imaging after stent placement has grown with improvements in image quality and speed of reconstruction. An automatic mechanical pullback device is used to withdraw the imaging catheter at a known and constant speed. Sequential two-dimensional tomographic images are then reconstructed by computer algorithm into an image that may

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be viewed in a three-dimensional format (Fig. 5). Increased echogenicity of a metallic stent, finite length, and reasonably straight course are well suited for three-dimensional reconstruction. Several investigators have demonstrated the feasibility of on-line and off-line three-dimensional image reconstruction after coronary stent placement.18,35, 43, 59 With further improvements in technology, electrocardiogram gating, and accuracy of spacial reconstruction, three-dimensional imaging may become the preferred method of assessing the results of endovascular stent placement. Superficial coronary calcium has been associated with incomplete stent expansion as assessed by either angiography or ultrasound. IVUS, however, has been demonstrated to detect target lesion calcium significantly more 58 Thereoften than standard angi~graphy.~~, fore, IVUS may be valuable to detect coronary calcium and guide rotational atherectomy before stent placement (Fig. 6). Clinical trials are in progress to assess the effect of IVUSdirected rotational atherectomy before stent placement on acute procedural results and long-term patient outcome. IVUS has also been used in a randomized clinical trial of catheter-based intraluminal radiation therapy to reduce intimal proliferation after stent placement.55,56 After reexpansion of a previously placed stent or stent placement in a restenotic lesion, IVUS is used to measure lumen and vessel dimensions, which are then used to determine radiation dosage via catheter well times.

Figure 5. Three-dimensional reconstruction of PalrnazSchatz coronary stent performed in vitro after placement in saphenous vein bypass graft.

SUMMARY

IVUS imaging has dramatically increased understanding of the process of coronary stent placement. Preintervention or diagnostic I W S has been shown to be of value before stent placement to assess lesion severity and length as well as the degree and location of calcification. Before stent placement, ultrasound dimensions may also be used to select the appropriate type and size of device. Although studies are in progress to define the role of prestent ultrasound imaging, much interest centers around the use of IVUS to detect significant superficial coronary calcium and direct rotational atherectomy before stent placement. Clinical trials have demonstrated the feasibility and safety of IVUS-guided coronary stent placement without postprocedure warfarin anticoagulation. Although it has been established subsequently that reduced anticoagulation may be administered to low-risk patients without IVUS guidance, three important points have been established by these trials. First, IVUS is superior to angiography for assessment of adequate stent expansion and apposition. As noted in several studies, angiography frequently overestimates lumen dimensions after stent placement. Second, IVUS-guided stent implantation yields larger acute stent dimensions. Third, IVUS-guided therapy in the form of additional stent placement or use of a larger balloon does not increase stent procedure complication rates when appropriate criteria for optimal stent placement are used. A randomized clinical trial (AVID) of angiography-directed versus IVUS-directed coronary stent placement is in progress (with a second soon to begin enrollment). In this trial, ultrasound guidance has been shown to improve acute procedural results, providing larger lumen dimensions without an increase in complication rates. IVUS guidance, however, does not appear to affect the incidence of stent thrombosis within 30 days in the present era of high-pressure balloon inflations and aggressive antiplatelet therapy. Results concerning the effect of ultrasound-guided therapy on long-term target lesion revascularization rates are pending. TO date, IVUS imaging has greatly contributed to advancements in coronary stent placement techniques. The future of NUS-guided coronary stent placement will, of course, de-

ULTRASOUND-GUIDED STENT PLACEMENT

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Figure 6. Coronary stent placement after intravascular ultrasound-directed rotational atherectomy. A, An intermediate lesion is noted in the distal portion of a right coronary artery. B, Ultrasound imaging reveals dense circumferential superficial calcium and an 80% cross-sectional area stenosis compared to the distal reference vessel. C,After sequential rotational atherectomy with 1.5- and 2.0rnm burrs, improvement in the angiographic appearance is noted. D,lntravascular ultrasound shows a significant reduction in lesion calcium. €, After placement of two Palrnaz-Schatz coronary stents, postdilated with a 3.5-mm balloon at 18 atm, an excellent angiographic result is obtained. F,A final stent diameter of 3.3 mm is measured by intravascular ultrasound.

pend on the results of several ongoing clinical trials. References 1. Allen KM, Undemir C, Shaknovich A, et al: Is there need for intravascular ultrasound after high-pressure dilatations of Palmaz-Schatz stents [abstr]. J Am Coll Cardiol27138A, 1996 2. Baim DS, Levine MJ, Leon MB, et a1 Management of restenosis within the Palmaz-Schatz coronary stent (The U.S. Multicenter Experience). J Am Coll Cardiol 71:36&366, 1993 3. Barragan P, Silvestri M, Sainsous J, et al: Prevention of subacute occlusion after coronary stenting with ticlopidine regimen without intravascular ultrasound guided stenting [abstr]. J Am Coll Cardiol 95:182A, 1995 4. Blasini R, Mudra H, Schiihlen H, et a1 Intravascular ultrasound guided optimized emergency coronary Palmaz Schatz stent placement without post procedural systemic anticoagulation [abstr]. J Am Coll Cardiol 26:197A, 1995 5. Caputo RP, Ho KKL, Lopez JJ, et al: Quantitative angiographic comparison of Palmaz-Schatz stent implantation with and without intravascular ultrasound [abstr]. Circulation 921-545, 1996

6. Caputo RP, Lopez JJ, Ho KKL, et al: Intravascular ultrasound analysis of routine high pressure balloon post-dilatation after Palmaz-Schatz stent deployment [abstr]. J Am Coll Cardiol 26:49A, 1995 7. Carrozza JP, Kuntz RE, Levine MJ, et al: Angiographic and clinical outcomes of intracoronary stenting: Immediate and long-term results from a large single-center experience. J Am Coll Cardiol 20328337, 1992 8. Colombo A, Hall P, Nakamura S, et al: Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 91: 16761688,1995 9. Colombo A, Itoh A, Hall P, et al: Results of intravascular ultrasound guided Palmaz-Schatz coronary stenting in a patient cohort equivalent to the BENES TENT study [abstr]. J Am Coll Cardiol27224A, 1996 10. Deaner ANS, Cubukcu AA, Rees M R Assessment of coronary stent by intravascular ultrasound. Int J Cardiol36:124-126, 1992 11. de Jaegere P, Mudra H, Almagor Y, et al: In-hospital and 1-month clinical results of an international study testing the concept of W S guided optimized stent expansion alleviating the need of systemic anticoagulation [abstr]. J Am Coll Cardiol 27137A, 1996 12. Ellis SG, Savage M, Fischman D, et a1 Restenosis after placement of Palmaz-Schatz stents in native coronary arteries: Initial results of a multicenter experience. Circulation 8618361844, 1992

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Address reprint requests to Robert J. Russo, MD, PhD Division of Cardiovascular Diseases, SW206 Scripps Clinic and Research Foundation 10666 North Torrey Pines Road La Jolla, CA 92037