Alexander J Wardeh

Geometric Vascular Remodeling After Balloon Angioplasty and β-Radiation Therapy: A Three-Dimensional Intravascular Ultrasound Study

BACKGROUND Endovascular radiation appears to inhibit intimal thickening after overstretching balloon injury in animal models. The effect of brachytherapy on vascular remodeling is unknown. The aim of the study was to determine the evolution of coronary vessel dimensions after intracoronary irradiation after successful balloon angioplasty in humans. METHODS AND RESULTS Twenty-one consecutive patients treated with balloon angioplasty and beta-radiation according to the Beta Energy Restenosis Trial-1.5 were included in the study. Volumetric assessment of the irradiated segment and both edges was performed after brachytherapy and at 6-month follow-up. Intravascular ultrasound images were acquired by means of ECG-triggered pullback, and 3-D reconstruction was performed by automated edge detection, allowing the calculation of lumen, plaque, and external elastic membrane (EEM) volumes. In the irradiated segments, mean EEM and plaque volumes increased significantly (451+/-128 to 490.9+/-159 mm(3) and 201.2+/-59 to 241.7+/-74 mm(3); P=0.01 and P=0.001, respectively), whereas luminal volume remained unchanged (250.8+/-91 to 249.2+/-102 mm(3); P=NS). The edges demonstrated an increase in mean plaque volume (26.8+/-12 to 32. 6+/-10 mm(3), P=0.0001) and no net change in mean EEM volume (71. 4+/-24 to 70.9+/-24 mm(3), P=NS), resulting in a decrease in mean luminal volume (44.6+/-16 to 38.3+/-16 mm(3), P=0.01). CONCLUSIONS A different pattern of remodeling is observed in coronary segments treated with beta-radiation after successful balloon angioplasty. In the irradiated segments, the adaptive increase of EEM volume appears to be the major contributor to the luminal volume at follow-up. Conversely, both edges showed an increase in plaque volume without a net change in EEM volume.

Radioactive Stents Delay but Do Not Prevent In-Stent Neointimal Hyperplasia

Background—Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. &bgr;-Particle–emitting radioactive stents decrease in-stent neointimal hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of 32P radioactive stents with an initial activity of 6 to 12 &mgr;Ci using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS). Methods and Results—Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (−0.43±0.56 mm;P =0.028) and in the mean lumen diameter in the stent (−0.55±0.63 mm;P =0.001); a significant increase in in-stent neointimal hyperplasia by IVUS (18.16±12.59 mm3 at 6 months to 27.75±11.99 mm3 at 1 year;P =0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free. Conclusions—Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 &mgr;Ci is not favorable when compared with conventional stenting.

Remodeling of Atherosclerotic Coronary Arteries Varies in Relation to Location and Composition of Plaque

The aim of this study was to determine the contribution of morphologic characteristics and location of plaque in remodeling of atherosclerotic coronary arteries. Consecutive intravascular ultrasound studies performed in native coronary arteries before an intervention were included in the study. Total vessel, lumen and plaque + media areas were measured at target lesion, and distal and proximal references. Remodeling index was calculated as target total vessel area/proximal reference total vessel area, and categorized into 3 groups based on relative total vessel-area ratio: (1) > 1.1 (group A, adequate remodeling); (2) 0.9 to 1.1 (group B, failure of compensatory enlargement); and (3) <0.9 (group C, coronary shrinkage). Eighty-nine narrowings were assessed in 80 intravascular ultrasound studies. Thirty-eight lesions (43%) were defined as soft and 51 (57%) as hard. Soft plaques were more prevalent in group A than in groups B and C (p = 0.001). Conversely, the arc of calcium was larger in group C lesions (p = 0.005). At distal segments, group A lesions were more prevalent than those in groups B and C, whereas at proximal segments group C lesions were more prevalent (p = 0.007). Multivariate analysis identified the arc of calcium and the location of plaque at distal segments as independent predictors of compensatory enlargement (odds ratio 0.94, 95% confidence interval 0.90 to 0.99; odds ratio 4.6; 95% confidence interval 1.4 to 15.7, respectively), whereas hard plaques were an independent predictor of coronary shrinkage (odds ratio 4.6; 95% confidence interval 1.7 to 12.5). In conclusion, composition and location of plaque appeared to be major determinants of vessel remodeling during the process of atherosclerosis.

Positive Geometric Vascular Remodeling Is Seen After Catheter-Based Radiation Followed by Conventional Stent Implantation but Not After Radioactive Stent Implantation

BackgroundRecent reports demonstrate that intracoronary radiation affects not only neointimal formation but also vascular remodeling. Radioactive stents and catheter-based techniques deliver radiation in different ways, suggesting that different patterns of remodeling after each technique may be expected. Methods and ResultsWe analyzed remodeling in 18 patients after conventional stent implantation, 16 patients after low-activity radioactive stent implantation, 16 patients after higher activity radioactive stent implantation, and, finally, 17 patients who underwent catheter-based radiation followed by conventional stent implantation. Intravascular ultrasound with 3D reconstruction was used after stent implantation and at the 6-month follow-up to assess remodeling within the stent margins and at its edges. Preprocedural characteristics were similar between groups. In-stent neointimal hyperplasia (NIH) was inhibited by high-activity radioactive stent implantation (NIH 9.0 mm3) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm3) compared with low-activity radioactive stent implantation (NIH 21.2 mm3) and conventional stent implantation (NIH 20.8 mm3) (P =0.008). No difference in plaque or total vessel volume was seen behind the stent in the conventional, low-activity, or high-activity stent implantation groups. However, significant increases in plaque behind the stent (15%) and in total vessel volume (8%) were seen in the group that underwent catheter-based radiation followed by conventional stent implantation. All 4 groups demonstrated significant late lumen loss at the stent edges; however, edge restenosis was seen only in the group subjected to high-activity stent implantation and appeared to be due to an increase in plaque and, to a lesser degree, to negative remodeling. ConclusionsDistinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting.

β-Particle–Emitting Radioactive Stent Implantation A Safety and Feasibility Study

Background—This study represents the Heart Center Rotterdam’s contribution to the Isostents for Restenosis Intervention Study, a nonrandomized multicenter trial evaluating the safety and feasibility of the radioactive Isostent in patients with single coronary artery disease. Restenosis after stent implantation is primarily caused by neointimal hyperplasia. In animal studies, b-particle‐ emitting radioactive stents decrease neointimal hyperplasia by inhibiting smooth muscle cell proliferation. Methods and Results—The radioisotope 32 P, a b-particle emitter with a half-life of 14.3 days, was directly embedded into the Isostent. The calculated range of radioactivity was 0.75 to 1.5 mCi. Quantitative coronary angiography measurements were performed before and after the procedure and at 6-month follow-up. A total of 31 radioactive stents were used in 26 patients; 30 (97%) were successfully implanted, and 1 was embolized. Treated lesions were in the left anterior descending coronary artery (n512), the right coronary artery (n58), or the left circumflex coronary artery (n56). Five patients received additional, nonradioactive stents. Treated lesion lengths were 13 64 mm, with a reference diameter of 2.9360.47 mm. Minimum lumen diameter increased from 0.8760.28 mm preprocedure to 2.8460.35 mm postprocedure. No in-hospital adverse cardiac events occurred. All patients received aspirin indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%) returned for 6-month angiographic follow-up; 17% of them had in-stent restenosis, and 13% had repeat revascularization. No restenosis was observed at the stent edges. Minimum lumen diameter at follow-up averaged 1.8560.69 mm, which resulted in a late loss of 0.9960.59 mm and a late loss index of 0.5360.35. No other major cardiac events occurred during the 6-month follow-up. Conclusions—The use of radioactive stents with an activity of 0.75 to 1.5 mCi is safe and feasible. (Circulation. 1999;100:1684-1689.)

Outcome from balloon induced coronary artery dissection after intracoronary beta radiation

OBJECTIVE To evaluate the healing of balloon induced coronary artery dissection in individuals who have received β radiation treatment and to propose a new intravascular ultrasound (IVUS) dissection score to facilitate the comparison of dissection through time. DESIGN Retrospective study. SETTING Tertiary referral centre. PATIENTS 31 patients with stable angina pectoris, enrolled in the beta energy restenosis trial (BERT-1.5), were included. After excluding those who underwent stent implantation, the evaluable population was 22 patients. INTERVENTIONS Balloon angioplasty and intracoronary radiation followed by quantitative coronary angiography (QCA) and IVUS. Repeat QCA and IVUS were performed at six month follow up. MAIN OUTCOME MEASURES QCA and IVUS evidence of healing of dissection. Dissection classification for angiography was by the National Heart Lung Blood Institute scale. IVUS proven dissection was defined as partial or complete. The following IVUS defined characteristics of dissection were described in the affected coronary segments: length, depth, arc circumference, presence of flap, and dissection score. Dissection was defined as healed when all features of dissection had resolved. The calculated dose of radiation received by the dissected area in those with healed versus non-healed dissection was also compared. RESULTS Angiography (type A = 5, B = 7, C = 4) and IVUS proven (partial = 12, complete = 4) dissections were seen in 16 patients following intervention. At six month follow up, six and eight unhealed dissections were seen by angiography (A = 2, B = 4) and IVUS (partial = 7, complete = 1), respectively. The mean IVUS dissection score was 5.2 (range 3–8) following the procedure, and 4.6 (range 3–7) at follow up. No correlation was found between the dose prescribed in the treated area and the presence of unhealed dissection. No change in anginal status was seen despite the presence of unhealed dissection. CONCLUSION β radiation appears to alter the normal healing process, resulting in unhealed dissection in certain individuals. In view of the delayed and abnormal healing observed, long term follow up is indicated given the possible late adverse effects of radiation. Although in this cohort no increase in cardiac events following coronary dissections was seen, larger populations are needed to confirm this phenomenon. Stenting of all coronary dissections may be warranted in patients scheduled for brachytherapy after balloon angioplasty.

Endovascular brachytherapy in coronary arteries: the Rotterdam experience

Purpose: The use of endovascular coronary brachytherapy to prevent restenosis following percutaneous transluminal coronary angioplasty (PTCA) began in April 1997 at the Department of Interventional Cardiology of the Thoraxcenter at the University Hospital of Rotterdam. This article reviews the more than 250 patients that have been treated so far.Methods and Materials: The Beta-Cath System (Novoste), a manual, hydraulic afterloader with 12 90Sr seeds, was used in the Beta Energy Restenosis Trial (BERT-1.5, n=31), for compassionate use (n=25), in the Beta-Cath System trial (n=27) and in the Beta Radiation in Europe (BRIE, n=14). Since the Beta-Cath System has been commercialized in Europe, 57 patients have been treated and registered in RENO (Registry Novoste). In the Proliferation Reduction with Vascular Energy Trial (PREVENT), 37 patients were randomized using the Guidant-Nucletron remote control afterloader with a 32P source wire and a centering catheter. Radioactive 32P coated stents have been implanted in 102 patients. In the Isostent Restenosis Intervention Study 1 (IRIS 1), 26 patients received a stent with an activity of 0.75-1.5 µCi, and in the IRIS 2 (European 32P dose response trial), 40 patients were treated with an activity of 6-12 µCi. In two consecutive pilot trials, radioactive stents with non-radioactive ends (cold-end stents) and with ends containing higher levels of activity (hot-end stents) were implanted in 21 and 17 patients, respectively.Results: In the BERT-1.5 trial, the radiation dose, prescribed at 2 mm from the source train (non-centered), was 12 Gy (10 patients), 14 Gy (10 patients) and 16 Gy (11 patients). At 6-month follow-up, 8 out of 28 (29%) patients developed restenosis. The target lesion revascularization rate (TLR) was 7 out of 30 (23%) at 6 months and 8 out of 30 (27%) at 1 year. Two patients presented with late thrombosis in the first year. For compassionate use patients, a restenosis rate (RR) of 53% was observed. In the PREVENT trial, 34 of 37 patients underwent an angiographic 6-month follow-up. The doses prescribed at 0.5 mm depth into the vessel wall were 0 Gy (8), 28 Gy (9), 35 Gy (11) and 42 Gy (8). TLR was 14% in the irradiated patients and 25% in the placebo group. One patient developed late thrombosis. In the IRIS 1 trial, 23 patients showed an RR of 17% (in-stent). In the IRIS 2 trial, in-stent restenosis was not seen in 36 patients at 6-month follow-up. However, a high RR (44%) was observed at the stent edges.Conclusions: The integration of vascular brachytherapy in the catheterization laboratory is feasible and the different treatment techniques that are used are safe. Problems, such as edge restenosis and late thrombotic occlusion, have been identified as limiting factors of this technique. Solutions have been suggested and will be tested in future trials.

Six-month outcome after excimer laser coronary angioplasty for diffuse in-stent restenosis in native coronary arteries.

This study evaluated the intermediate-term follow-up after excimer laser coronary angioplasty (ELCA) and adjunctive percutaneous transluminal coronary angioplasty (PTCA) in patients with diffuse in-stent restenosis (lesion length >10 mm). Clinical and angiographic follow-up were performed at 6 months. Quantitative coronary angiography performed at 3 stages-during stent implantation, before and after ELCA + PTCA, and at follow-up-included measurements of the minimum lumen diameter (MLD) and percent diameter stenosis (DS). Sixteen consecutive patients were included. The (median + range) stent length was 36 mm (range 15 to 105), with a restenotic lesion length of 32 mm (range 10 to 90). After ELCA + PTCA, the MLD increased from 0.60 +/- 0.41 to 2.28 +/- 0.50 mm, whereas the DS decreased from 76 +/- 16% to 22 +/- 8%. Despite adjunctive high-pressure PTCA, the MLD after ELCA + PTCA remained smaller than the MLD after initial stent implantation, (2.28 +/- 0. 50 mm vs 2.67 +/- 0.32 mm, p = 0.014). Adverse events included ELCA-related acute coronary occlusion in 4 patients and a per-procedural intracerebral hematoma in 1. At 6 months, there was recurrence of angina in all patients. Angiographic follow-up was completed in 13 patients (87%), showing a reocclusion in 6 (46%), a >50% DS in 6 (MLD 1.03 +/- 0.87 mm, DS 68 +/- 24%), and a distal de novo lesion in 1. Despite satisfactory acute angiographic results, the recurrence of significant restenosis in all patients suggests that ELCA + PTCA is not a suitable stand-alone therapy for diffuse in-stent restenosis of long stented segments.

Volume coronary angiography using targeted scans (VCATS): a new strategy in MR coronary angiography.

The aim of this study was to explore the clinical possibilities of a new strategy for magnetic resonance imaging of the coronary arteries. Thirteen patients were studied by volume coronary angiography using targeted scans (VCATS) to visualize the major coronary arteries in a series of breath-holds. The proximal coronary arteries were clearly seen in 92% and the mid segments in 50–70% of the patients. VCATS was able to visualize a total vessel length of the left main (LM) (mean: 9.4 ± 3.4 mm), of the left anterior descending (LAD) 69 ± 20 mm, of the right coronary artery (RCA) 90 ± 33 mm and of the left circumflex (LCX) 41 ± 18 mm. There was a reasonable correlation between the VCATS and conventional coronary angiography (CAG) for vessel diameter (r = 0.71), with a slight overestimation of 0.7 mm by VCATS. There were nine significant stenoses present of which six were correctly detected, three were missed and one false positive was present. VCATS is fast strategy for visualizing the major coronary artery branches and has the potential to detect significant stenoses in these branches.

Low rates of clinical restenosis with the new flexible stainless steel tube intracoronary stent: the R Stent. A six-month safety and feasibility study

BACKGROUND: Coronary stents have been used with increasing frequency and in increasingly complex coronary lesions for the treatment of symptomatic coronary artery disease. A new stainless steel coronary stent, the R Stent, has been designed to provide maximum flexibility for tracking and high radial strength postdeployment. AIMS: To assess the safety and feasibility of the R Stent in patients with coronary artery disease. Specific objectives were to assess the R Stents deployment success, angiographic and procedural success (< 20% residual stenosis and TIMI 3 flow), safety (absence of complications), 30-day and six-month clinical follow-up. METHODS: Between April 1998 and January 1999, stent deployment was attempted in 36 lesions in 30 patients with stable (43%) or unstable (57%) angina pectoris and 29/36 of the lesions were anatomically complex. Treated lesions were in the LAD ( n = 15), RCA ( n = 13) or LCX ( n = 8). RESULTS: Stent deployment was achieved in 97% with one crossing failure in a patient with a long, calcified, proximal LAD lesion. After the procedure, patients were scheduled for one- and six-month clinical follow-up. One patient experienced a non-Q-wave myocardial infarction in hospital. At one month, there were no additional complications. Only one patient experienced recurrence of angina (CCS class 2) within the 30 days. At six-month follow-up, one sudden death had occurred. Three (10%) patients had anginal complaints, one of them received target lesion repeat PTCA. All other patients (87%) were event- and angina-free. CONCLUSION: This first clinical experience with the R Stent shows acceptable feasibility and safety with good long-term clinical results. (Int J Cardiovasc Intervent 2000; 3: 91-95)