Local vessel injury following percutaneous coronary intervention does not promote early mobilisation of endothelial progenitor cells in the absence of myocardial necrosis.

BACKGROUND/OBJECTIVES: Endothelial progenitor cells (EPCs) are circulating mononuclear cells that are released from the bone marrow in response to injury and participate in vascular repair. Some previous studies have suggested an early mobilisation of EPCs following percutaneous coronary intervention (PCI) that could modulate the subsequent risk of restenosis or stent thrombosis. However, those studies did not discriminate between vascular injury caused by PCI and any associated myocardial injury. Myocardial injury alone can influence EPC mobilisation in a non-specific manner, and could therefore confound any association with risk. We investigated the effect of local endothelial trauma following PCI on EPC mobilisation in the absence of myocyte necrosis. DESIGN: We quantified circulating EPCs from 20 patients immediately before, 6 hours and 24 hours following elective PCI in patients without a 24-hour troponin rise. Absolute counts of EPCs expressing combinations of CD45, CD34, CD133 and kinase domain receptor (KDR) were recorded using flow cytometry. RESULTS: There was a fall of 7-15% in EPC numbers between baseline and 6 hours post procedure and a subsequent rise (5-18%) from 6 hours to 24 hours. At 24 hours EPC levels were similar to baseline. CONCLUSIONS: The specific localised vascular injury induced by PCI did not lead to early mobilisation of EPCs. However, the fall in EPCs 6 hours after PCI was significant and its relation to early post-PCI complications such as stent thrombosis requires further exploration.

Serial intravascular ultrasound assessment of the efficacy of intracoronary gamma radiation for preventing recurrent in-stent restenosis.

Intracoronary stents reduce restenosis compared with balloon angioplasty. However, a major limitation of stenting is in-stent restenosis, which occurs in 10% to 40% of the patients depending upon risk factors. Serial intravascular ultrasound studies have shown that in-stent restenosis is primarily due to neointimal hyperplasia. Treatment of in-stent restenosis is challenging and recurrence rates are high regardless of interventional technique used. Several randomized clinical trials with intracoronary ionizing radiation using both beta (b) and gamma (g) emitters following primary catheter-based intervention have demonstrated a significant reduction in recurrence. The majority of these studies have used both serial angiographic and serial intravascular ultrasound endpoints to assess the efficacy of intracoronary radiation to prevent recurrence after the treatment of in-stent restenosis. As different mechanism of postradiation restenosis may operate in the original lesion segment, the ballooned segment and the actual irradiated segment, these imaging techniques have also helped to document any long-term affects of radiation including aneurysm formation, edge effects, geographical miss, and the presence or absence of remodeling. The angiographic results have correlated well with intravascular ultrasound results after radiation therapy and at follow-up. Thus, a combination of both serial intravascular ultrasound and careful angiography, which documents balloon, stent, and radiation source positioning, can fully assess the effectiveness of this modality of treatment.

Comparative efficacy of gamma-irradiation for treatment of in-stent restenosis in saphenous vein graft versus native coronary artery in-stent restenosis: An intravascular ultrasound study.

BACKGROUND: We used serial volumetric (post-irradiation and follow-up) intravascular ultrasound (IVUS) to compare the effectiveness of gamma-irradiation ((192)Ir) in saphenous vein graft (SVG) versus native coronary artery in-stent restenosis (ISR). METHODS AND RESULTS: The study population consisted of 47 patients with native coronary artery ISR from WRIST (Washington Radiation for In-Stent Restenosis Trial) and 31 patients with SVG ISR (12 from the WRIST and 19 from SVGWRIST). After irradiation and at 6-month follow-up, stent, lumen, and intimal hyperplasia (IH, stent minus lumen) areas were measured every 1 mm. ISR length was similar in the 2 groups (29+/-12 versus 29+/-14 mm, P=0.9). Post-intervention measurements of stent (280+/-154 versus 324+/-270 mm(3), P=0.4), lumen (184+/-91 versus 214+/-172 mm(3), P=0.3), and IH (96+/-77 versus 109+/-119 mm(3), P=0.5) volumes were similar in the 2 groups. The post-intervention minimum lumen cross sectional areas tended to be smaller in native artery ISR lesions (4.7+/-1.7 versus 5.4+/-1.6 mm(2), P=0.11). During follow-up, there was a slight increase in IH volume (9+/-38 mm(3)) in native artery ISR lesions and a slight decrease in IH volume in SVG ISR lesions (-9+/-32 mm(3), P=0.0463). There was also a slight decrease in minimum lumen area in the native artery ISR lesions versus a slight increase in minimum lumen area in the SVG ISR lesions (-0.8+/-1.7 versus 0.2+/-1.1, P=0.0087). As a result, the follow-up minimum lumen area in native artery lesions was smaller than in SVG ISR lesions (4.1+/-2.1 mm(2) versus 5.6+/-2.2 mm(2), P=0.0067). CONCLUSION: gamma-Irradiation with (192)Ir brachytherapy appears to be as effective in SVGs as it is in native artery ISR lesions.

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%).

An intravascular ultrasound classification of angiographic coronary artery aneurysms.

The purpose of this study was to use intravascular ultrasound (IVUS) to clarify the morphology of coronary aneurysms diagnosed by angiography. Seventy-seven consecutive patients with an aneurysmal dilatation in a native coronary artery diagnosed by angiography (defined as a lesion lumen diameter 25% larger than reference) were evaluated by IVUS. IVUS true aneurysms were defined as having an intact vessel wall and a maximum lumen area 50% larger than proximal reference. IVUS pseudoaneurysms had a loss of vessel wall integrity and damage to adventitia or perivascular tissue. Complex plaques were lesions with ruptured plaque or spontaneous or unhealed dissection. Aneurysmal dilatation and reference segments were assessed using standard IVUS quantitative techniques. Twenty-one lesions (27%) were classified as true aneurysms, 3 (4%) were classified as pseudoaneurysms, 12 (16%) were complex plaques, and the other 41 (53%) were normal arterial segments adjacent to > or =1 stenosis. The maximum lumen area within the aneurysmal segment was largest for pseudoaneurysm (35.1 +/- 10.4 mm(2)), 22.1 +/- 9.9 mm(2) for true aneurysm, and similar for complex plaques (11.2 +/- 3.5 mm(2)) and normal segments with adjacent stenoses (13.8 +/- 6.4 mm(2)): analysis of variance, p <0.0001. Only one third of angiographically diagnosed aneurysms had the IVUS appearance of a true or pseudoaneurysm. Instead, most angiographically diagnosed aneurysms had the morphology of complex plaques or normal segments with adjacent stenoses.

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 edge recurrence after intracoronary gamma radiation treatment of native artery in-stent restenosis lesions.

In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients were first treated with conventional techniques and then randomized to either gamma-irradiation ((192)Ir) or placebo (dummy seeds). In the (192)Ir group with native coronary in-stent restenosis, we identified 8 patients with edge recurrence and compared them with 21 patients with no recurrence. Serial (postirradiation and follow-up) intravascular ultrasound analysis was performed according to conventional methods. When compared with nonrecurring lesions, lesions with distal edge recurrence had (1) greater decrease in mean distal lumen cross-sectional area (-3.0 +/- 1.2 vs -0.7 +/- 1.0 mm(2), p = 0.0002), (2) no change in mean distal external elastic membrane cross-sectional area versus an increase in mean distal cross-sectional area of 1.0 +/- 0.9 mm(2) in nonrecurring lesions (p = 0.0047), and (3) a greater increase in mean distal plaque + media cross-sectional area (2.9 +/- 1.2 mm vs 1.7 +/- 0.6 mm(2), p = 0.0103). Within the stented segment, the nonrecurring lesions had no decrease in mean lumen and no increase in mean intimal hyperplasia cross-sectional area. Conversely, lesions with distal edge recurrence had a significant decrease in mean intrastent lumen cross-sectional area (-1.7 +/- 1.7 mm(2)) and a significant increase in mean intrastent intimal hyperplasia cross-sectional area (1.6 +/- 1.6 mm(2)). Lesions with distal edge recurrence also had a greater decrease in mean proximal lumen cross-sectional area (-1.7 +/- 1.3 vs -0.3 +/- 0.8 mm(2), p = 0.0213), with a trend toward a greater increase in mean proximal plaque + media cross-sectional area. Thus, edge recurrence after (192)Ir treatment of in-stent restenosis is the result of neointimal hyperplasia (part of generalized treatment failure) and the absence of radiation-induced positive remodeling.

Influence of gender on early and one-year clinical outcomes after saphenous vein graft stenting.

Compared with men, women may have a worse prognosis after native coronary revascularization. However, the influence of gender on clinical outcomes after saphenous vein graft (SVG) stenting is unknown. The purpose of this study was to compare early and 1-year clinical outcomes between men and women after stent implantation in SVG. A total of 1,199 consecutive patients with 1,858 SVG lesions were studied. Procedural success, in-hospital events, and late clinical outcomes were compared between men (n = 951) and women (n = 248). Overall procedural success was similar between men and women (97% vs 96%, p = NS). However, in-hospital (3.2% vs 1.6%, p = 0.07) and 30-day cumulative (4.4% vs 1.9%, p = 0.02) mortality rates were higher in women than in men. In addition, women had a higher incidence of vascular complications (12% vs 7.3%, p = 0.006) and postprocedural acute renal failure (8.1% vs 4%, p = 0.02). At 1-year follow-up, mortality was 13% in women and 11% in men (p = NS) and target lesion revascularization was 18% versus 23%, respectively (p = NS). By multivariate regression analysis, independent correlates of in-hospital mortality were female gender (odds ratio [OR] 3.6, confidence interval [CI] 1.0 to 12.5, p = 0.05) and left ventricular ejection fraction (OR 0.9, CI 0.9 to 1.0, p = 0.01). Female gender was found to predict 30-day mortality (OR 2.5, CI 1.1 to 5.5, p = 0.02). The sole predictor of 1-year mortality was diabetes mellitus (OR 1.6, CI 1.1 to 2.3, p = 0.01). This study shows that women compared with men treated with stent implantation in SVG lesions have (1) a trend toward higher in-hospital mortality, (2) higher risk of 30-day mortality, (3) increased incidence of vascular complications and postprocedure acute renal failure, and (4) similar 1-year clinical outcome.

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.

Influence of diabetes mellitus on early and late clinical outcomes in saphenous vein graft stenting.

OBJECTIVES: The purpose of this study was to compare early and late clinical outcomes in diabetic and nondiabetic patients after stent implantation in saphenous vein grafts (SVG). BACKGROUND: Patients with diabetes mellitus have less favorable acute and long-term outcomes after stent implantation in native coronary arteries. The impact of diabetes on SVG stenting, however, is not known. METHODS: We studied 908 consecutive patients (1,366 SVG lesions) treated with Palmaz-Schatz stents. In-hospital and late clinical outcomes (death, Q-wave myocardial infarction and repeat revascularization rates at one year) were compared between diabetic (n = 290) and nondiabetic (n = 618) patients. RESULTS: In-hospital mortality was significantly higher in diabetic as compared with nondiabetic patients (2.2% vs. 0.3%, p = 0.003). At one-year follow-up, target lesion revascularization (TLR) was 16.6% in diabetic and 12.3% in nondiabetic patients (p = 0.03). Overall cardiac event-free survival (freedom from death, Q-wave myocardial infarction and any coronary revascularization procedure) at one year was significantly lower in the diabetic (68%) compared with the nondiabetic patients (79%, p = 0.0003). By Cox regression analysis, diabetes mellitus was an independent predictor of both TLR (relative risk: 1.23; confidence interval: 0.96 to 1.58; p = 0.004) and late cardiac events (relative risk: 1.40; confidence interval: 1.05 to 1.86; p = 0.02). CONCLUSIONS: Patients with diabetes undergoing stent implantation in SVG have: 1) higher in-hospital and late mortality, 2) higher one-year TLR rates, and 3) significantly lower one-year cardiac event-free survival. Thus, diabetic patients have less favorable acute and late clinical outcomes after stent implantation in SVG lesions.

Assessing a strategy of initial stand-alone extractional atherectomy followed by staged stent placement in degenerated saphenous vein graft lesions.

To assess whether a staged strategy (initial stand alone transluminal extraction atherectomy and coumadin therapy followed by stenting six weeks later) could reduce ischemic complications in degenerated saphenous vein graft (SVG) interventions, we studied 72 patients undergoing percutaneous interventions of degenerated SVG. Patients were divided into two groups; 28 were treated with a staged strategy (group I) and 44 with similar lesion characteristics were treated with a definitive initial procedure with transluminal extraction atherectomy +/- adjunctive balloon angioplasty and stenting (group II). Procedural success, major in-hospital complications (death, Q-wave myocardial infarction, and emergent coronary bypass surgery), and incidence of distal embolization were compared between the 2 groups. Procedural success was lower (92% vs 100%, p = 0.14) and major in-hospital complications were higher (0% vs 11%, p = 0.14) in group II. Distal embolization occurred in 11% of the patients in group I compared with 23% of the patients in group II (p = 0.19). At 6 week follow-up (group I), 9 patients (33%) had negative symptoms, 11 (41%) underwent stent implantation, 3 (11%) did not require any further therapy (without significant stenosis), and 4 (14%) had total occlusions. We therefore conclude that this staged strategy in degenerated SVG appears to reduce distal embolization but most importantly avoids major in-hospital complications, including any deaths either at the time of initial procedure or during the 6-week follow-up period.

Mechanism of lumen enlargement during intracoronary stent implantation: an intravascular ultrasound study.

BACKGROUND: Intravascular ultrasound analysis has assessed mechanisms of lumen enlargement after nonstent interventions, but not after stenting. METHODS AND RESULTS: Preintervention and postintervention intravascular ultrasound was used to study 25 de novo native coronary lesions treated with single MultiLink stents without preatheroablation. External elastic membrane, lumen, and plaque and media (P&M) areas were measured every 1 mm to include the lesion and reference segments that were 5 mm proximal and distal to it. Lesion mean lumen area increased from 4.0+/-1.0 mm(2) before the intervention to 8.8+/-2.0 mm(2) after the intervention (P<0.0001) as a result of an increase in mean external elastic membrane area (14. 2+/-2.7 to 16.1+/-3.0 mm(2), P<0.0001) and a decrease in mean P&M area (10.2+/-2.2 to 7.2+/-1.8 mm(2), P<0.0001). The decrease in lesion P&M was accompanied by an increase in both proximal reference mean P&M (7.0+/-1.9 to 8.4+/-2.0 mm(2), P<0.0001) and distal reference mean P&M (5.8+/-2.1 to 7.2+/-2.1 mm(2), P<0.0001). Volumetric analysis showed an axial redistribution of plaque away from the center of the lesion toward the reference segments to increase the plaque burden in both the proximal and distal reference segments. Total (lesion plus reference) mean P&M decreased from 8. 6+/-2.1 to 7.5+/-1.8 mm(2) (P<0.0001). CONCLUSIONS: The mechanisms of lumen enlargement after stenting involved (1) significant axial redistribution of plaque from the lesion into the reference segments, (2) vessel expansion, and (3) either plaque embolization or compression.

Safety of intracoronary gamma-radiation on uninjured reference segments during the first 6 months after treatment of in-stent restenosis: a serial intravascular ultrasound study.

BACKGROUND: The effects of endovascular irradiation on uninjured reference segments during the treatment of in-stent restenosis are unknown. METHODS AND RESULTS: In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized (blinded) to receive either gamma-irradiation ((192)Ir) or a placebo (dummy seeds). We identified all patients in whom the active (n=19) or dummy seeds (n=19) extended >10 mm proximal and distal to the in-stent restenosis lesion. Serial (postirradiation and follow-up) external elastic membrane (EEM), lumen, and plaque and media (EEM-lumen) areas were measured (using intravascular ultrasound) every 1 mm over 5-mm-long reference segments that were 6 to 10 mm proximal and distal to the in-stent restenosis lesion. During follow-up, a similar small increase occurred in the plaque and media area in the proximal and distal reference segments in both (192)Ir and placebo patients. However, in the (192)Ir patients, an increase in both proximal and distal EEM area occurred; as a result, no change in lumen area occurred. Conversely, in the placebo patients, the proximal reference EEM area decreased, and no change occurred in the distal reference EEM area; this contributed to a decrease in lumen area. CONCLUSIONS: There was no evidence of a deleterious effect of gamma-irradiation on angiographically normal uninjured reference segments in the first 6 months after the treatment of in-stent restenosis.

Comparison of debulking followed by stenting versus stenting alone for saphenous vein graft aortoostial lesions: immediate and one-year clinical outcomes.

OBJECTIVES: We compared in-hospital and one-year clinical outcomes in patients undergoing debulking followed by stent implantation versus stenting alone for saphenous vein graft (SVG) aortoostial lesions. BACKGROUND: Stent implantation in SVG aortoostial lesions may improve procedural and late clinical outcomes. However, the impact of debulking before stenting in this complex lesion subset is unknown. METHODS: We studied 320 consecutive patients (340 SVG aortoostial lesions) treated with Palmaz-Schatz stents. Debulking with excimer laser or atherectomy was performed in 133 patients (139 lesions) before stenting (group I), while 187 patients (201 lesions) underwent stent implantation without debulking (group II). Procedural success and late clinical outcomes were compared between the groups. RESULTS: Overall procedural success (97.6%) was similar between the groups. Procedural complications were also similar (2.2% for group I and 2.6% for group II). At one-year follow-up, target lesion revascularization (TLR) was 19.4% for group I and 18.2% for group II (p = 0.47). There was no difference in cumulative death or Q wave myocardial infarction between the groups. Overall cardiac event-free survival was similar (69% for group I and 68% for group II). By Cox regression analysis, the independent predictors of late cardiac events were final lumen cross-sectional area (CSA) by intravascular ultrasound (IVUS) (p = 0.001) and restenotic lesions (p = 0.01). Similarly, final IVUS lumen CSA (p = 0.0001) and restenotic lesions (p = 0.006) were found to predict TLR at one year. CONCLUSIONS: These results suggest that, in most patients with SVG aortoostial lesions, debulking before stent implantation may not be necessary.

Severe spasm of the free radial artery graft in a patient undergoing high-risk angioplasty under percutaneous cardiopulmonary support.

This report illustrates a case of percutaneous intervention in a very high-risk patient who already had three previous bypass operations and was not a suitable candidate for further surgical revascularization. Since intra-aortic balloon pump insertion was contraindicated due to the origin of a radial graft from the descending aorta, percutaneous cardiopulmonary support (CPS) was used to perform the procedure. Thus, CPS proved useful in providing adequate hemodynamic support and allowed us to use adequate amount of antispastic drugs to relieve any spasm during the procedure. This case also highlights the need to use antispastic drugs before performing percutaneous interventions on arterial conduits, particularly radial artery grafts which are prone to vasospasm. Since the use of the radial artery for bypass surgery has recently been revived with considerable interest, perhaps more percutaneous interventional procedures may be performed in the future on arterial graft stenosis. We therefore recommend the routine use of vasorelaxant drugs in percutaneous interventions involving arterial grafts.