The contribution of "mechanical" problems to in-stent restenosis: An intravascular ultrasonographic analysis of 1090 consecutive in-stent restenosis lesions.

OBJECTIVES: Serial intravascular ultrasonographic (IVUS) studies have shown that in-stent restenosis is the result of intimal hyperplasia (IH). However, routine preintervention IVUS imaging has suggested that many restenotic stents were inadequately deployed. The purpose of this IVUS study was to determine the incidence of mechanical problems contributing to in-stent restenosis (ISR). METHODS: Between April 1994 and June 2000, 1090 patients with ISR were treated at the Washington Hospital Center. All underwent preintervention IVUS imaging. IVUS measurements included proximal and distal reference lumen areas and diameters; stent, minimum lumen, and IH (stent minus lumen) areas; and IH burden (IH/stent area). RESULTS: In 49 ISR lesions (4.5%), there were morphologic findings that contributed to the restenosis. These were termed mechanical complications. Examples include (1) missing the lesion (eg, an aorto-ostial stenosis), (2) stent "crush," and (3) having the stent stripped off the balloon during the implantation procedure. Excluding mechanical complications, stent underexpansion was common. In 20% of the ISR cases the stents had a cross-sectional area (CSA) at the site of the lesion <80% of the average reference lumen area. Twenty percent of lesions had a minimum stent area <5.0 mm(2) and an additional 18% had a minimum stent area of 5.0 to 6.0 mm(2). Twenty-four percent of lesions had an IH burden <60%. CONCLUSION: Mechanical problems related to stent deployment procedures contribute to a significant minority of ISR lesions (approximately 25%).

Serial intravascular ultrasound assessment of the efficacy of intracoronary gamma-radiation therapy for preventing recurrence in very long, diffuse, in-stent restenosis lesions.

BACKGROUND: The efficacy of coronary gamma-irradiation in preventing recurrent in-stent restenosis (ISR) is well established. However, brachytherapy may be less effective in very long, diffuse ISR lesions. METHODS AND RESULTS: We used serial intravascular ultrasound (IVUS) to study patients with long, diffuse ISR lesions (length, 36 to 80 mm) who were enrolled in (1) Long WRIST (Washington Radiation In-Stent Restenosis Trial), a double-blind, placebo-controlled trial of intracoronary gamma-irradiation (15 Gy at 2 mm from the source) and (2) high-dose (HD) Long WRIST, a registry that used a dose prescription of 18 Gy at 2 mm from the source. IVUS was performed using automated pullback (0.5 mm/s). Stent, lumen, and intimal hyperplasia were measured at 2-mm intervals. Complete postintervention and follow-up IVUS imaging was available in 30 irradiated and 34 placebo patients from Long WRIST and in 25 patients from HD Long WRIST. Stent length was longer in HD Long WRIST than in placebo or treated patients in Long WRIST (P=0.0064 and P=0.0125, respectively). Otherwise, baseline measurements were similar. At follow-up, the minimum lumen area was largest in the HD Long WRIST patients (4.0+/-1.4 mm(2)); areas were 2.9+/-1.0 mm(2) in irradiated patients in Long WRIST and 1.9+/-1.1 mm(2) in placebo patients in Long WRIST (P<0.005 for all comparisons). CONCLUSIONS: - Serial IVUS analysis shows that gamma-irradiation reduces recurrent in-stent neointimal hyperplasia in long, diffuse ISR lesions; however, it is even more effective when given at a higher dose.

Serial intravascular ultrasound analysis of the impact of lesion length on the efficacy of intracoronary gamma-irradiation for preventing recurrent in-stent restenosis.

BACKGROUND: The relation between lesion length and effectiveness of brachytherapy is not well studied. METHODS AND RESULTS: We compared serial (postintervention and follow-up) intravascular ultrasound findings in 66 patients with native coronary artery in-stent restenosis (ISR) who were treated with (192)Ir (15 Gy delivered 2 mm away from the radiation source). Patients were enrolled in the Washington Radiation for In-Stent Restenosis Trial (WRIST; ISR length, 10 to 47 mm; n=36) or Long WRIST (ISR length, 36 to 80 mm; n=30). External elastic membrane, stent, lumen, and intimal hyperplasia (IH; stent minus lumen) areas and source-to-target (intravascular ultrasound catheter to external elastic membrane) distances were measured. Postintervention stent areas were larger in WRIST and smaller in Long WRIST patients (P:<0.0001). At follow-up, maximum IH area significantly increased in both WRIST and Long WRIST patients (P:<0.0001 for both), but this increase was greater in Long WRIST patients (P:=0.0006). Similarly, minimum lumen cross-sectional area significantly decreased in both WRIST and Long WRIST patients (P:<0.05 and P:<0.0001, respectively), but this decrease was more pronounced in Long WRIST patients (P:=0.0567). The maximum source-to-target distance was longer in Long WRIST than in WRIST, and it correlated directly with ISR length (r=0.547, P:<0.0001). Overall, the change in minimum lumen area and the change in maximum IH area correlated with the maximum source-to-target distance (r=0.352, P:=0.0038 and r=0.523, P:<0.0001 for WRIST and Long WRIST, respectively). The variability (maximum/minimum) in IH area at follow-up also correlated with the maximum source-to-target distance (r=0.378, P:<0.0001). CONCLUSIONS: Brachytherapy may be less effective in longer ISR lesions because of the greater variability and longer source-to-target distances in diffuse ISR.

Effect of preintervention plaque burden on subsequent intimal hyperplasia in stented coronary artery lesions.

We sought to determine if axial and circumferential distribution of plaque before stenting determines the axial and circumferential distribution of subsequent intimal hyperplasia (IH). We studied 22 patients with a single Palmaz-Schatz stent implanted in a native coronary artery, who underwent intravascular ultrasound (IVUS) imaging before intervention, after stenting, and at 6-month follow-up. For each lesion, 7 locations were analyzed: proximal and distal reference, proximal and distal edge of the stent, proximal and distal location within the body of the stent, and the articulation. Pre- and postintervention and follow-up image slices were precisely aligned and analyzed for pre- and postintervention plaque area and follow-up IH area and thickness. The location of maximal IH area was at or adjacent to the location of maximal preintervention plaque in 17 of 22 of the patients (77%). Similiarly, the circumferential distribution of IH at follow-up paralleled the eccentricity pattern of the native plaque burden in 69% (24 of 35 slices). Using multivariant analysis, the strongest predictor of IH was preintervention plaque area (p = 0.001). IH accumulates axially and circumferentially preferentially at the site of maximal preintervention plaque.

Acute and long-term results of an intravascular ultrasound-guided percutaneous transluminal coronary angioplasty/provisional stent implantation strategy.

Two hundred eighty-four consecutive patients with 438 native coronary artery stenoses were enrolled prospectively in a study of intravascular ultrasound (IVUS)-guided provisional percutaneous transluminal coronary angioplasty (PTCA): (1) IVUS-guided, aggressive lesion-site media-to-media balloon sizing, (2) IVUS assessment of residual lumen dimensions to identify optimal PTCA results (minimum lumen area > or =65% of the average of the proximal and distal reference lumen areas or > or =6.0 mm2 and no major dissection), and (3) liberal stent crossover. Overall, 206 stenoses in 134 patients were treated with PTCA alone. Reasons for crossover were flow-limiting or lumen compromising dissections in 28% of patients or a suboptimal IVUS minimum lumen area in 72% of patients. Sixty-three stenoses (27%) were treated with Gianturco-Roubin stents and 169 (73%) with Palmaz-Schatz stents. The clinical success rate and major in-hospital complication rates were similar in the optimal PTCA and stent crossover groups. At 1 year, 42 patients (15%) with 53 stenoses (12%) underwent revascularization: 8% of stenoses in the PTCA group and 16% in the stent crossover group. In approximately half of the patients treated using an IVUS guided aggressive PTCA strategy, stent implantation could be avoided without sacrificing an increase in acute complications or late clinical outcome. This provides an alternative strategy for interventionalists less inclined to use routine elective stenting.

Serial volumetric intravascular ultrasound assessment of arterial remodeling in left main coronary artery disease.

Serial volumetric intravascular ultrasound (IVUS) was used to study de novo, nontreated left main coronary arteries (LMCAs) in 31 patients. Using an automated contour detection algorithm, analysis of 7.2 +/- 2.5 mm long segments included arterial, lumen, and plaque volumes and plaque burden (plaque/arterial volumes). During follow-up (7.7 +/- 2.4 months), the percent change in lumen volume correlated with the percent change in arterial volume (r = 0.897, p <0.0001), but not with the percent change in plaque volume (r = 0.066, p = 0.7263). Percent changes in arterial volume correlated with percent changes in plaque + media volume (r = 0.448, p = 0.0115), indicating arterial remodeling. However, there was a spectrum of responses ranging from inadequate remodeling (decrease in lumen volume despite no increase or a decrease in plaque volume: i.e., arterial shrinkage) to overcompensation (an increase in lumen volume despite an increase in plaque volume). Serial volumetric IVUS (1) confirms the existence of both positive and negative remodeling in LMCA, and (2) shows that in moderate LMCA disease, luminal changes resulted primarily from positive versus negative remodeling, not plaque progression and/or regression.