Wim J. van der Giessen

Late Coronary Occlusion After Intracoronary Brachytherapy

BACKGROUND Intracoronary brachytherapy appears to be a promising technology to prevent restenosis. Presently, limited data are available regarding the late safety of this therapeutic modality. The aim of the study was to determine the incidence of late (>1 month) thrombosis after PTCA and radiotherapy. METHODS AND RESULTS From April 1997 to March 1999, we successfully treated 108 patients with PTCA followed by intracoronary beta-radiation. Ninety-one patients have completed at least 2 months of clinical follow-up. Of these patients, 6.6% (6 patients) presented with sudden thrombotic events confirmed by angiography 2 to 15 months after intervention (2 balloon angioplasty and 4 stent). Some factors (overlapping stents, unhealed dissection) may have triggered the thrombosis process, but the timing of the event is extremely unusual. Therefore, the effect of radiation on delaying the healing process and maintaining a thrombogenic coronary surface is proposed as the most plausible mechanism to explain such late events. CONCLUSIONS Late and sudden thrombosis after PTCA followed by intracoronary radiotherapy is a new phenomenon in interventional cardiology.

Inhibition of Restenosis With β-Emitting Radiotherapy Report of the Proliferation Reduction With Vascular Energy Trial (PREVENT)

BackgroundIntracoronary &ggr;- and &bgr;-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of &bgr;-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. Methods and ResultsA prospective, randomized, sham-controlled study of intracoronary radiotherapy with the &bgr;-emitting 32P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11±36% in radiotherapy patients versus 55±30% in controls (P <0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (≥50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%;P =0.012) and at target site plus adjacent segments (22% versus 50%;P =0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%;P <0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. Conclusions&bgr;-radiotherapy with a centered 32P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.

Optical coherence tomography patterns of stent restenosis

BACKGROUND Stent restenosis is an infrequent but poorly understood clinical problem in the drug-eluting stent era. The aim of the study was to evaluate the morphologic characteristics of stent restenosis by optical coherence tomography (OCT). METHODS Patients (n = 24, 25 vessels) presenting with angiographically documented stent restenosis were included. Quantitative OCT analysis consisted of lumen and stent area measurement and calculation of restenotic tissue area and burden. Qualitative restenotic tissue analysis included assessment of tissue structure, backscattering and symmetry, visible microvessels, lumen shape, and presence of intraluminal material. RESULTS By angiography, restenosis was classified as diffuse, focal, and at the margins in 9, 11, and 5 vessels, respectively. By OCT, restenotic tissue structure was layered in 52%, homogeneous in 28%, and heterogeneous in 20%. The predominant backscatter was high in 72%. Microvessels were visible in 12%. Lumen shape was irregular in 28% and there was intraluminal material in 20%. The mean restenotic tissue symmetry ratio was 0.58 +/- 0.19. Heterogeneous and low scattering restenotic tissue was more frequent in focal (45.5% and 54.5%, respectively) than in diffuse (0 and 11.1%) and margin restenosis (0 and 0%) (P = .005 for heterogeneous, P = .03 for low scattering). Restenosis patients with unstable angina symptoms presented more frequently irregular lumen shape (60 vs 6.7%, P = .007). Stents implanted </=12 months ago had more frequently restenotic tissue with layered appearance (84.6% vs 16.7%, P = .003). CONCLUSIONS We demonstrate the ability of OCT to identify differential patterns of restenotic tissue after stenting. This information could help in understanding the mechanism of stent restenosis.

Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation: long-term (up to 2 years) clinical, angiographic, and intravascular ultrasound follow-up

Background—Early results of sirolimus-eluting stent implantation showed a nearly complete abolition of neointimal hyperplasia. The question remains, however, whether the early promising results will still be evident at long-term follow-up. The objective of our study was to evaluate the efficiency of sirolimus-eluting stent implantation for up to 2 years of follow-up. Methods and Results—Fifteen patients with de novo coronary artery disease were treated with 18-mm sirolimus-eluting Bx-Velocity stents (Cordis) loaded with 140 &mgr;g sirolimus/cm2 metal surface area in a slow release formulation. Quantitative angiography (QCA) and intravascular ultrasound (IVUS) were performed according to standard protocol. Sirolimus-eluting stent implantation was successful in all 15 patients. During the in-hospital course, 1 patient died of cerebral hemorrhage after periprocedural administration of abciximab, and 1 patient underwent repeat stenting after 2 hours because of edge dissection that led to acute occlusion. Through 6 months and up to 2 years of follow-up, no additional events occurred. QCA analysis revealed no significant change in stent minimal lumen diameter or percent diameter stenosis, and 3-dimensional IVUS showed no significant deterioration in lumen volume. In 2 patients, additional stenting was performed because of significant lesion progression remote from the sirolimus-eluting stent. Conclusion—Sirolimus-eluting stents showed persistent inhibition of neointimal hyperplasia for up to 2 years of follow-up.

Strain distribution over plaques in human coronary arteries relates to shear stress

Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into four regions: upstream, throat, shoulder, and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat, and downstream region was 2.55+/-0.89, 2.07+/-0.98, 2.32+/-1.11, and 0.67+/-0.35 Pa, respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23+/-0.08% vs. 0.48+/-0.15%, 0.43+/-0.17%, and 0.47+/-0.12%, for the upstream, shoulder, and throat regions, respectively). Pooling all regions, dividing shear stress per plaque into tertiles, and computing average strain showed a positive correlation; for low, medium, and high shear stress, strain was 0.23+/-0.10%, 0.40+/-0.15%, and 0.60+/-0.18%, respectively. Low strain colocalizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with the highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture.

Long-term clinical outcome after stent implantation in saphenous vein grafts

OBJECTIVES We sought to determine the role of stent implantation in vein grafts by evaluating the long-term clinical outcome and estimated event-free survival at 5 years in 62 patients and by comparing our data with those of other treatment modalities previously reported. BACKGROUND Patients with recurrent angina after coronary artery bypass graft surgery pose a problem. Stent implantation has been advocated in an effort to avoid repeat operation and to address the limitations of balloon angioplasty. METHODS Patients undergoing stenting of a vein graft were entered into a dedicated data base. They were screened for death, infarction, bypass surgery and repeat angioplasty. Procedure-related events were included in the follow-up analysis. Survival and event-free survival curves were constructed by the Kaplan Meier method. RESULTS A total of 93 stents (84 Wallstent and 9 Palmaz-Shatz) were implanted in 62 patients. During the in-hospital period seven patients (11%) sustained a major cardiac event: two deaths (3%), two myocardial infarctions (3%) and three urgent bypass surgeries (5%). The clinical success rate, therefore, was 89%. During the follow-up period (median 2.5 years, range 0 to 5.9), another five patients (8%) died, 14 (23%) sustained a myocardial infarction, 12 (20%) underwent bypass surgery, and 14 (23%) underwent angioplasty. The estimated 5-year survival and event-free survival rates (free from infarction, repeat surgery and repeat angioplasty) were (mean +/- SD) 83 +/- 5% (95% confidence interval [CI] 73% to 93%) and 30 +/- 7% (95% CI 16% to 44%), respectively. CONCLUSIONS The in-hospital outcome of patients who underwent stent implantation in a vein graft is acceptable, but the long-term clinical outcome is poor. It is unlikely that mechanical intervention alone will provide a satisfactory or definite answer for the patient with graft sclerosis over the long term.

Electrocardiogram-Gated Intravascular Ultrasound Image Acquisition After Coronary Stent Deployment Facilitates On-Line Three-Dimensional Reconstruction and Automated Lumen Quantification ☆

OBJECTIVE This study evaluates the feasibility, reliability and reproducibility of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) image acquisition during automated transducer withdrawal and automated three-dimensional (3D) boundary detection for assessing on-line the result of coronary stenting. BACKGROUND Systolic-diastolic image artifacts frequently limit the clinical applicability of such automated analysis systems. METHODS In 30 patients, after successful angiography-guided implantation of 34 stents in 30 target lesions, we carried out IVUS examinations on-line with the use of ECG-gated automated 3D analyses and conventional manual analyses of two-dimensional images from continuous pullbacks. These on-line measurements were compared with off-line 3D reanalyses. The adequacy of stent deployment was determined by using ultrasound criteria for stent apposition, symmetry and expansion. RESULTS Gated image acquisition was successfully performed in all patients to allow on-line 3D analysis within 8.7 +/- 0.6 min (mean +/- SD). Measurements by on-line and off-line 3D analyses correlated closely (r > or = 0.95), and the minimal stent lumen differed only minimally (8.6 +/- 2.8 mm2 vs. 8.5 +/- 2.8 mm2, p = NS). The conventional analysis significantly overestimated the minimal stent lumen (9.0 +/- 2.7 mm2, p < 0.005) in comparison with results of both 3D analyses. Fourteen stents (41%) failed to meet the criteria by both 3D analyses, all of these not reaching optimal expansion, but only 7 (21%) were detected by conventional analysis (p < 0.02). Intraobserver and interobserver comparison of stent lumen measurements by the automated approach revealed minimal differences (0.0 +/- 0.2 mm2 and 0.0 +/- 0.3 mm2) and excellent correlations (r = 0.99 and 0.98, respectively). CONCLUSIONS ECG-gated image acquisition after coronary stent deployment is feasible, permits on-line automated 3D reconstruction and analysis and provides reliable and reproducible measurements; these factors facilitate detection of the minimal lumen site.

NIRS and IVUS for characterization of atherosclerosis in patients undergoing coronary angiography

OBJECTIVES The aim of this study was to compare the findings of near-infrared spectroscopy (NIRS), intravascular ultrasound (IVUS) virtual histology (VH), and grayscale IVUS obtained in matched coronary vessel segments of patients undergoing coronary angiography. BACKGROUND Intravascular ultrasound VH has been developed to add tissue characterization to the grayscale IVUS assessment of coronary plaques. Near-infrared spectroscopy is a new imaging technique able to identify lipid core-containing coronary plaques (LCP). METHODS We performed NIRS and IVUS-VH pullbacks in a consecutive series of 31 patients with a common region of interest (ROI) between 2 side branches. For each ROI, we analyzed the chemogram blocks by NIRS, plaque area and plaque burden by grayscale IVUS, and tissue types by IVUS-VH. The chemogram block is a summary metric of a 2-mm vertical slice of the chemogram. The value ranges from 0 to 1 according to the presence of lipids and represents the probability of LCP with a color scale from red (low probability) through orange and tan to yellow (high probability). RESULTS Plaque area (mm(2)) increases as percentage VH derived-necrotic core (NC) content (4.6 ± 2.7 vs. 7.4 ± 3.5 vs. 8.6 ± 3.4 vs. 7.9 ± 3.3, grouped in percentage NC quartiles, p<0.001) and chemogram block probability color bin thresholds increase (4.9 ± 3.8 red, 7.3 ± 3.6 orange, 8.1 ± 3.4 tan, and 8.7 ± 3.4 yellow, p<0.001). The correlation between the block chemogram detection of lipid core and percentage NC content by VH was weak (r=0.149). Correction for the presence of calcium does not improve this correlation. CONCLUSIONS Larger plaque area by grayscale IVUS was more often associated with either elevated percentage VH-NC or LCP by NIRS; however, the correlation between the detection of LCP by NIRS and necrotic core by VH is weak.

Intracoronary Heparin Delivery in Humans: Acute Feasibility and Long-term Results

BACKGROUND Inefficacy of systemic drug administration for restenosis prevention may partially relate to insufficient local drug concentration. This study aimed to evaluate the acute feasibility and long-term outcome of using an infusion-perfusion coil balloon, Dispatch. METHODS AND RESULTS In 22 patients after balloon angioplasty, the coil balloon was studied for (1) feasibility of local heparin delivery, (2) symptoms and signs of ischemia during prolonged deployment compared with angioplasty balloon occlusion, (3) coronary pressure and flow distal to the inflated device, and (4) long-term clinical and angiographic results. During prolonged intracoronary deployment of the coil balloon (29 +/- 8 minutes), 5 of 22 patients developed mild chest pain versus 20 of 22 during angioplasty (275 +/- 283 seconds). Neither hemodynamic nor vectorcardiographic signs of ischemia were detected, in contrast to angioplasty balloon occlusion. Baseline flow across the coil balloon was 44 +/- 31 mL/min, increasing by a factor of 1.8 +/- 0.7 during pharmacologically induced hyperemia. A mean volume of 14.2 +/- 6.1 mL containing 1416 +/- 608 IU of heparin was infused locally at a pressure of 122 +/- 54 mm Hg. At 7 +/- 1-month follow-up, 1 asymptomatic patient had died, and of the remaining 21, 17 (81%) were asymptomatic. Angiographic follow-up was obtained in 15 of 21 patients (71%), including all 4 symptomatic patients. Mean minimal luminal diameter after the procedure was 2.16 +/- 0.49 mm and at follow-up, 1.89 +/- 0.45 mm, which corresponds to a restenosis rate (diameter stenosis > or = 50%) of 7% (1/15). CONCLUSIONS Intracoronary use of the coil balloon after balloon angioplasty proved to be feasible and subjectively as well as objectively well tolerated during prolonged deployment by virtue of its perfusion properties. High volumes of heparin solution can be infused locally at very low pressure. No unfavorable clinical or angiographic long-term effects were observed.

Four-year follow-up of treatment with intramyocardial skeletal myoblasts injection in patients with ischaemic cardiomyopathy

AIMS Studies reporting improved left ventricular (LV) function of percutaneous skeletal myoblast (SkM) injection in patients with ischaemic cardiomyopathy had follow-up not exceeding 12 months, and did not include a control group. Our group has reported evidence for myoblast efficacy in the first five out of the 14 treated patients. The objective of the present evaluation was to assess if these effects were sustained at long-term follow-up. We compared function of patients treated with SkM 4 years earlier with a matched control group. Secondary endpoints included mortality, NYHA class, N-terminal pro-B-natriuretic peptide levels, incidence of arrhythmias, and quality of life. METHODS AND RESULTS Fourteen patients with ischaemic cardiomyopathy who underwent SkM injection were compared with 28 non-randomized control patients matched for age, sex, location, and extent of myocardial infarction. Contrast echocardiography and tissue Doppler imaging (TDI) was performed to compare global and regional LV function. At 4-year follow-up, three patients (21%) had died in the treated group and 11 patients (39%) in the control group (P = 0.8). In the survivors, LV ejection fraction (EF) was 35 +/- 10% and 37 +/- 9% in the SkM group and 36 +/- 8% and 36 +/- 6% in the controls at baseline and 4 years follow-up, respectively (P = 0.96 between groups at follow-up). TDI-derived systolic velocity in the injected sites was 5.4 +/- 1.8 cm/s in the SkM group when compared with 5.1 +/- 1.6 cm/s in corresponding sites in the control group (P = 0.47). None of the secondary endpoints showed a difference between the groups. However, in the patients fitted with an internal cardioverter defibrillator, more arrhythmias leading to interventions occurred in the treated group than in the control group, 87% and 13%, respectively (P = 0.015). CONCLUSION Percutaneous intramyocardial SkM injection in ischaemic cardiomyopathy has no sustained positive effect on resting global or regional LV function, respectively, at 4-year follow-up. Moreover, the procedure may induce a higher risk of developing serious arrhythmias, but larger patient series are required before more precise characterization of the safety and efficacy profile of the procedure is possible.