Comparison of Immediate and Intermediate-Term Results of Intravascular Ultrasound Versus Angiography-Guided Palmaz-Schatz Stent Implantation in Matched Lesions

Background Intravascular ultrasound (IVUS) provides more precise information than angiography about vascular dimensions. This information is used by some centers to optimize intracoronary stent implantation. There are no direct comparisons of the effects on restenosis of optimal IVUS-guided versus angiography-directed high-pressure stenting. Methods and Results Lesions of patients who had a 6-month angiographic follow-up study were eligible for matching. From 445 consecutive lesions treated by Palmaz-Schatz (P-S) stenting guided by IVUS (IVUS group) in Milan, 173 lesions were individually matched with 173 of 476 consecutive lesions treated by P-S stenting directed by angiography (Angio group) in Hamburg. Lesions were selected by a computerized program according to baseline clinical, angiographic, and procedural variables. Immediate and 6-month angiographic results were retrospectively compared, distinguishing an “early phase” from a “late phase.” This distinction was based on the more aggressive dilation strategy with larger balloons and more demanding IVUS criteria for optimal stent expansion used in Milan in the early phase. In both phases, a larger minimum lumen diameter (MLD) immediately after stenting and after 6 months was achieved in the IVUS group than in the Angio group. In the early phase, the dichotomous restenosis rate was lower in the IVUS group than in the Angio group (9.2% versus 22.3%; P =.04). In the late phase, there was no difference in restenosis between the groups (22.7% versus 23.7%; P =1.0). Conclusions In matched lesions treated with high-pressure stenting, IVUS guidance achieved a larger MLD than angiographic guidance. However, in the IVUS group, the restenosis rate was lower only in the early phase, when balloons larger than currently used were selected to maximize the stent lumen area. dextran (dextran 40, given at a dose of 100 mL/h for 2 hours before stenting and at a dose of 50 mL/h during and after the procedure, for a total volume of 1 L). A bolus of 10 000 U heparin was given after sheath insertion, with a repeat bolus of 5000 U given as needed to maintain the activated clotting time >250 seconds in Milan or hourly in the event of a prolonged procedure in Hamburg. Only P-S tubular slotted stents (Johnson & Johnson Interventional Systems) were implanted in the patients who entered this study: the standard 15-mm PS153 stent with a central linear articulation, a disarticulated 7-mm PS153 stent, a 14-mm PS154 stent, a 10-mm PS104 stent, an 18-mm PS204 stent with multiple spiral bridges, a 10-mm biliary stent, and a 20-mm renal stent. For calculating the number of stents per lesion, the short stents (<10 mm) were counted as half stents. Biliary stents were counted as one stent each. All other stents were counted as one stent. Indications for stenting and their definitions were as previously reported. and intraobserver variability. The diameters of the proximal and distal lumen reference segments were averaged to obtain a mean reference diameter. MLD and % DS were measured in the baseline, posttreatment, and follow-up angiograms. Lesion length was measured on the baseline angiogram as the distance between the proximal and distal shoulders of the lesion, detected as the point at which the lumen becomes compromised by 50%. Lesions were characterized according to the modified American College of Cardiology/American Heart Association score. Thrombus was defined as a filling defect seen in multiple projections surrounded by contrast in the absence of calcification. ⇑ , the was slight and did not into a lower restenosis rate (22.7% versus 23.7%; P =1.0). Our findings confirm the importance of the immediate result in determining the late result, by Kuntz et but deviate from the model of restenosis proposed by these authors in that the higher acute gain observed in the IVUS group versus the Angio group was not associated with a greater late loss, which was similar (1.0 to 1.1 mm) in the two groups in both phases. Coronary artery stenting prevents negative remodeling; thus, late loss within a stent results almost exclusively from intimal hyperplasia, as recently demonstrated by a serial IVUS study. The present study demonstrates that in the IVUS group, the more aggressive balloon dilation strategy used in the early phase, which possibly increased vessel wall injury, was not accompanied by a greater hyperplastic response. A possible mechanism for this result could be that after stenting, the extent of subsequent intimal hyperplasia is more dependent on plaque mass before intervention, as we clear selection bias was introduced, including only the patients who had a follow-up angiographic study. However, the results observed in this selected population are likely to reflect the results of the overall population. The patients were selected by a computerized procedure from a larger patient cohort, which can be considered representative of the initial cohorts. In fact, in both centers after stenting, all patients were scheduled for a coronary angiography at 6 months, and a similar percentage of patients (61.4% of the Milan population versus 71.9% of the Hamburg population) had an angiographic follow-up. The rest did not undergo a repeat angiographic study, mostly because they were asymptomatic and refused the study.


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In this page In a new window Download as PowerPoint Slide CSA equal to or greater than the distal reference lumen CSA. In this phase, IVUS-guided stent optimization was generally performed with noncompliant balloons inflated at high pressure. The balloons were selected with a calculated nominal CSA 25% to 30% larger than distal lumen CSA, based on the observation that the ratio of the final stent CSA to the calculated nominal balloon CSA was 0.75 to 0.80 in the early phase. The rapid change in the final balloon-to-artery ratio over time in Milan, reflecting the change in IVUS-guided balloon selection compared with Hamburg (angiography-guided), is shown in Fig 1⇓. The third IVUS criterion for optimal stent expansion was that the nonstented adjacent inflow and outflow segments should not reveal evidence of a significant lesion, defined as plaque area >60% of the total vessel lumen.

Figure 1.
Smoothed curve plot (moving average of 7 data points) of ratio of nominal diameter of final balloon selected to angiographic reference vessel diameter in Milan and Hamburg over time. In Hamburg, dilation strategy did not change over this time period. In Milan, when target for defining IVUS success was achievement of 60% of average of proximal and distal total vessel CSA, postdilations were performed with balloons angiographically oversized (early phase). From September 1993, IVUS criterion for optimal stent expansion was rapidly altered (late phase). Goal was to achieve stent CSA equal to or greater than distal lumen CSA. In this phase, use of smaller balloons inflated at higher pressure resulted in significantly lower balloon-to-artery ratio than in early phase.

Angiographic Analysis
Both in Milan and in Hamburg, coronary angiograms were analyzed by experienced technicians not involved in the stenting procedure. Angiographic measurements of baseline, final, and follow-up angiograms were performed in a single matched view (working projection) at end diastole. The lesions were measured with a digital electronic caliper (Brown and Sharp) from an optically magnified image. The guiding catheter was used as the scaling device for calibration. Previous studies have shown that digital calipers correlate closely with computer-assisted methods, with a low interobserver and intraobserver variability.
The diameters of the proximal and distal lumen reference segments were averaged to obtain a mean reference diameter. MLD and % DS were measured in the baseline, posttreatment, and follow-up angiograms. Lesion length was measured on the baseline angiogram as the distance between the proximal and distal shoulders of the lesion, detected as the point at which the lumen becomes compromised by 50%. Lesions were characterized according to the modified American College of Cardiology/American Heart Association score.
Thrombus was defined as a filling defect seen in multiple projections surrounded by contrast in the absence of calcification.

Patient, Baseline Angiographic, and Procedural Characteristics
The baseline clinical characteristics of the patients in the IVUS (173 lesions in 158 patients) and Angio (173 lesions in 154 patients) groups are shown in Table 1⇓. In the Angio group, compared with the IVUS group, left ventricular ejection fraction was higher, the number of patients with two-vessel disease was lower, there were more patients with three-vessel disease and hypercholesterolemia, and fewer patients were current smokers. Sex, previous angioplasty at the same site, diabetes, and unstable angina were not different between the two groups. Matching for angiographic and procedural variables resulted in two groups of lesions with superimposable baseline angiographic and procedural characteristics. In the Angio group, however, the percentage of calcific lesions identified by angiography was lower than that in the IVUS group (Table 2⇓). Furthermore, in the Angio group, the percentage of lesions in which a half stent per lesion was deployed was higher, with a lower percentage of lesions in which one and two stents per lesion were implanted (Table 3⇓). Consequently, in the Angio group, the mean total number of stents per lesion was slightly lower (1.05±0.46 versus 1.17±0.44, P=.014).

Baseline Clinical Characteristics
Ta ble 2.

Clinical Events
As shown in Table 4⇓, no stent thrombosis occurred in either group. Moreover, the percentages of patients who had MI and CABG during hospitalization and after discharge were not statistically different between the groups. The percentage of patients who needed a repeat percutaneous intervention during follow-up was lower in the IVUS group than in the Angio group (5.1% versus 11.7%; P=.05). However, the percentage of patients who needed a repeat revascularization (CABG+PTCA) was not significantly different between the groups (7% versus 11.7%; P=.17). Table 5⇓ summarizes the quantitative angiographic results of the matched lesions in the IVUS and Angio groups during the early phase and the late phase. Reference vessel diameter, MLD, and %DS immediately before stenting were similar in the IVUS and Angio groups, indicating that the matching process was adequate.

Comparison of Quantitative Angiographic Results of the Matched Lesions in the Early Phase and Late Phase
As illustrated in Fig 2⇓, IVUS-guided stent deployment produced a significantly greater acute gain than angiography-guided stenting in both the early phase and the late phase. A similar late loss of 1.0 to 1.1 mm was observed at 6-month follow-up angiography in the two groups in both phases. This resulted in a higher net gain and a lower loss index in the IVUS group than in the Angio group, with a statistically significant difference in the early phase, which translated into a lower dichotomous restenosis rate (9.2% versus 22.3%; P=.04). In the late phase, there was no difference in restenosis between the groups (22.7% versus 23.7%; P=1.0). Furthermore, in the early phase, the balloons used to optimize stent expansion were larger in the IVUS group than in the Angio group, with a higher balloon-to-artery ratio (Fig 1⇑). In the late phase, although the size of the final balloon was greater in the IVUS group than in the Angio group, the balloon-to-artery ratio was not different between the groups. In addition, in the early phase, the maximal balloon inflation pressure was lower in the IVUS group than in the Angio group. Finally, lesions were slightly longer in the IVUS group than in the Angio group. However, the calculated total length of the stented lesion was not different between the groups.  have recently reported, with the preintervention plaque area measured by IVUS, than on the greater final strain (overstretch) applied to the vessel wall by a larger balloon correctly sized to the media-to-media vessel dimensions.
Late loss (and restenosis) has been reported to be influenced by some clinical, angiographic, and procedural factors. The effects of these factors in our study were well balanced in the two groups; in particular, the higher percentages of patients with hypercholesterolemia and three-vessel disease in the Angio group were counterbalanced by the lower percentage of patients currently smoking, by the slightly shorter lesion length, and by the lower percentage of calcific lesions. Furthermore, the differences in the type and number of stents per lesion were negligible. In fact, in Milan, two disarticulated 7-mm-long PS153 stents, instead of one standard 15-mm-long PS153 stent, were implanted in 53% of the lesions in which only disarticulated PS153 stents were implanted. This result is also inferable by the fact that, although the percentage of half stents implanted was higher in the IVUS than in the Angio group (46.2% versus 28.1%), the percentage of lesions in which only a half stent was implanted was lower in the IVUS group (6.9% versus 20.2%). Finally, although the mean number of stents per lesion was higher in the IVUS than in the Angio group (1.17 versus 1.05), the majority of patients had one stent per lesion, and the calculated stented lesion length was equal in both groups in both phases (Table 5⇑). Other established risk factors for restenosis (diabetes, unstable angina, and chronic total occlusion) were not different between the groups.
After stenting, the inhibition of intimal hyperplasia would be the ideal therapy to reduce restenosis. The results of the present study indicate that restenosis can also be reduced mechanically by trying to achieve as large an MLD as possible and that IVUS is better than angiography guidance to achieve this goal, because angiography may underestimate the extent of atherosclerotic disease in coronary arteries that undergo compensatory enlargement, thus leading to underestimation of the size of the final balloon that can be selected to safely expand the stent and maximize the stent lumen CSA. The use of IVUS guidance allows one to better oversize the balloon (by angiography) and to obtain a larger final MLD that would not be achieved by inflating a smaller balloon at higher pressure.

IVUS-Guided Stent Optimization
In the early phase, IVUS-guided stent optimization was performed with larger balloons than in the late phase, and with this strategy, a greater increase in the stent CSA was obtained after stent optimization (51±36% versus 28±35%; P=.002). Although there was no difference in the angiographic reference vessel diameter, the vessel CSA measured at the distal reference site by IVUS was significantly smaller in the lesions treated during the late phase as a result of a lower percentage of plaque area. However, this finding cannot by itself explain the lower increase in CSA achieved in the late phase, which probably would have been greater if the final balloons selected had been larger and sized to the IVUS average distal vessel diameter.

IVUS Guidance Permits the Use of Balloons Traditionally Considered Oversized
In the IVUS group, in the 76 matched lesions treated in the early phase, there were no more complications or vessel ruptures, compared with the 97 lesions treated in the late phase and with the lesions in the Angio group, suggesting that in the presence of arterial remodeling identified by IVUS, target lesions can safely accommodate larger balloons. This hypothesis is supported by the favorable results of the CLOUT trial, in which oversized balloons were safely used in 73% of the lesions in which IVUS identified the presence of arterial remodeling and the absence of heavy calcification.