Three-dimensional intravascular ultrasound assessment of noninjured edges of beta-irradiated coronary segments.

BACKGROUND: The "edge effect," late lumen loss at the margins of the treated segment, has become an important issue in the field of coronary brachytherapy. The aim of the present study was to assess the edge effect in noninjured margins adjacent to the irradiated segments after catheter-based intracoronary beta-irradiation. METHODS AND RESULTS: Fifty-three vessels were assessed by means of 3-dimensional intravascular ultrasound after the procedure and at 6- to 8-month follow-up. Fourteen vessels (placebo group) did not receive radiation (sham source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5 mm in length) were identified as noninjured, whereas 18 noninjured edges were selected in the placebo group. We compared the volumetric intravascular ultrasound measurements of the noninjured edges of the irradiated vessels with the fully irradiated nonstented segments (IRS, n=27) (26-mm segments received the prescribed 100% isodose) and the noninjured edges of the vessels of the placebo patients. The lumen decreased (6 mm(3)) in the noninjured edges of the irradiated vessels at follow-up (P:=0. 001). We observed a similar increase in plaque volume in all segments: noninjured edges of the irradiated group (19.6%), noninjured edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume increased in the IRS in the 3 groups. No edge segment was subject to repeat revascularization. CONCLUSIONS: The edge effect occurs in the noninjured margins of radiation source train in both irradiated and placebo patients. Thus, low-dose radiation may not play an important role in this phenomenon, whereas nonmeasurable device injury may be considered a plausible alternative explanation.

Positive geometric vascular remodeling is seen after catheter-based radiation followed by conventional stent implantation but not after radioactive stent implantation.

BACKGROUND: Recent 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 RESULTS: We 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 mm(3)) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm(3)) compared with low-activity radioactive stent implantation (NIH 21.2 mm(3)) and conventional stent implantation (NIH 20.8 mm(3)) (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. CONCLUSIONS: Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting.

Angiographical follow-up after radioactive "Cold Ends" stent implantation: a multicenter trial.

BACKGROUND: Radioactive stents with an activity of 0.75 to 12 microCi have shown >40% edge restenosis due to neointimal hyperplasia and negative remodeling. This trial evaluated whether radioactive Cold Ends stents might resolve edge restenosis by preventing remodeling at the injured extremities. METHODS AND RESULTS: The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends) Cold Ends stents had an activity of 3 to 12 microCi at implantation. Forty-three stents were implanted in 43 patients with de novo native coronary artery disease. Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis rate of 22% was observed with a shift of the restenosis, usually occurring at the stent edges of radioactive stents, into the Cold Ends stents. The most severe restenosis occurred at the transition zone from radioactive to nonradioactive segments, a region located in dose fall-off. CONCLUSION: Cold Ends stents did not resolve edge restenosis.

Radioactive stents delay but do not prevent in-stent neointimal hyperplasia.

BACKGROUND: Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. Beta-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 (32)P radioactive stents with an initial activity of 6 to 12 microCi 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 mm(3) at 6 months to 27.75+/-11. 99 mm(3) 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 microCi is not favorable when compared with conventional stenting.

Geographic miss: a cause of treatment failure in radio-oncology applied to intracoronary radiation therapy.

BACKGROUND: A recognized limitation of endovascular beta-radiation therapy is the development of new stenosis at the edges of the irradiated area. The combination of injury and low-dose radiation may be the precursor of this phenomenon. We translated the radio-oncological concept of "geographic miss" to define cases in which the radiation source did not fully cover the injured area. The aims of the study were to determine the incidence and causes of geographic miss and evaluate the impact of this inadequate treatment on the outcome of patients treated with intracoronary beta-radiation. METHODS AND RESULTS: We analyzed 50 consecutive patients treated with beta-radiation after percutaneous coronary intervention. The prescribed dose ranged between 12 and 20 Gy at 2 mm from the source axis. By means of quantitative coronary angiography, the irradiated segment (IRS) and both edges were studied before and after intervention and at 6-month follow-up. Edges that were injured during the procedure constituted the geographic miss edges. Twenty-two edges were injured during the intervention, mainly because of procedural complications that extended the treatment beyond the margins of the IRS. Late loss was significantly higher in geographic miss edges than in IRSs and uninjured edges (0.84+/-0.6 versus 0.15+/-0.4 and 0.09+/-0.4 mm, respectively; P<0.0001). Similarly, restenosis rate was significantly higher in the injured edges (10% within IRS, 40.9% in geographic miss edges, and 1.9% in uninjured edges; P<0.001). CONCLUSIONS: These data support the hypothesis that the combination of injury and low-dose beta-radiation induces deleterious outcome.

Sustained suppression of neointimal proliferation by sirolimus-eluting stents: one-year angiographic and intravascular ultrasound follow-up.

BACKGROUND: We have previously reported a virtual absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting stents. The aim of the present investigation was to determine whether these results are sustained over a period of 1 year. METHODS AND RESULTS: Forty-five patients with de novo coronary disease were successfully treated with the implantation of a single sirolimus-eluting Bx VELOCITY stent in São Paulo, Brazil (n=30, 15 fast release [group I, GI] and 15 slow release [GII]) and Rotterdam, The Netherlands (15 slow release, GIII). Angiographic and volumetric intravascular ultrasound (IVUS) follow-up was obtained at 4 and 12 months (GI and GII) and 6 months (GIII). In-stent minimal lumen diameter and percent diameter stenosis remained essentially unchanged in all groups (at 12 months, GI and GII; at 6 months, GIII). Follow-up in-lesion minimal lumen diameter was 2.28 mm (GIII), 2.32 mm (GI), and 2.48 mm (GII). No patient approached the >/=50% diameter stenosis at 1 year by angiography or IVUS assessment, and no edge restenosis was observed. Neointimal hyperplasia, as detected by IVUS, was virtually absent at 6 months (2+/-5% obstruction volume, GIII) and at 12 months (GI=2+/-5% and GII=2+/-3%). CONCLUSIONS: This study demonstrates a sustained suppression of neointimal proliferation by sirolimus-eluting Bx VELOCITY stents 1 year after implantation.

Methodological and clinical implications of the relocation of the minimal luminal diameter after intracoronary radiation therapy. Dose Finding Study Group.

OBJECTIVES: The aims of the study were to determine the incidence of relocation of the minimal luminal diameter (MLD) after beta-radiation therapy following balloon angioplasty (BA) and to describe a new methodological approach to define the effect of brachytherapy on treated coronary stenoses. BACKGROUND: Luminal diameter of coronary lesions may increase over time following angioplasty and irradiation. As a result, the MLD at follow-up may be relocated from its location preintervention, which may induce misleading results when a restricted definition of the target segment by quantitative coronary angiography (QCA) is performed. METHODS: Patients treated with BA followed by intracoronary brachytherapy according to the Dose-Finding Study constituted the study population. A historical cohort of patients treated with BA was used as control group. To be included in the analysis, an accurate angiographic documentation of all instrumentations during the procedure was mandatory. In the irradiated patients, four regions were defined by QCA: vessel segment (VS), target segment (TS), injured segment (INS), and irradiated segment (IRS). RESULTS: Sixty-five patients from the Dose-Finding Study and 179 control patients were included. At follow-up, MLD was relocated more often in the radiation group (78.5% vs. 26.3%; p < 0.0001). The rate of >50% diameter stenosis differed among the four predefined regions: 3.1% in the TS; 7.7% in the INS; 9.2% in the IRS and 13.8% in the VS. CONCLUSIONS: Relocation of the MLD is commonly demonstrated after BA and brachytherapy, and it should be taken into account during the analysis of the results of radiation clinical trials.

Geographical miss during catheter-based intracoronary beta-radiation: incidence and implications in the BRIE study. Beta-Radiation In Europe.

OBJECTIVES: We sought to determine the incidence and causes of geographical miss (GM) and to evaluate its impact on edge restenosis after intracoronary beta-radiation therapy. BACKGROUND: Edge restenosis is a limitation of intracoronary beta-radiation therapy. Geographical miss is the situation in which the radiation source does not fully cover the injured segment and may lead to edge restenosis. METHODS: We analyzed 175 vessels treated according to the Beta-Radiation In Europe (BRIE) study protocol. The effective irradiated segment (EIRS) and both edges were studied with quantitative coronary angiography. The edges of the EIRS that were injured constituted the GM edges. Restenosis was defined as diameter stenosis >50% at follow-up. Geographical miss was determined by simultaneous electrocardiographic-matched, side-by-side projection of the source and balloons deflated at the injury site, in identical angiographic projections surrounded by contrast. RESULTS: Geographical miss affected 41.2% of the edges and increased edge restenosis significantly compared with non-GM edges (16.3% vs. 4.3%, respectively, p = 0.004). Restenosis was increased both in the proximal (p = 0.05) and distal (p = 0.02) GM edges compared with noninjured edges. Geographical miss associated with stent injury significantly increased edge restenosis (p = 0.006), whereas GM related to balloon injury did not significantly increase edge restenosis (p = 0.35). The restenosis in the EIRS was similar between vessels with and without GM (24.3% and 21.6%, respectively, p = 0.8). CONCLUSIONS: Geographical miss is strongly associated with restenosis at the edges of the EIRS. This effect is more prominent when caused by stenting. Geographical miss does not increase restenosis in the EIRS.

Angiographic and clinical outcome of mild to moderate nonocclusive unstented coronary artery dissection and the influence on coronary flow velocity reserve. The Debate I Study Group.

Limited data are available regarding the angiographic healing rate and physiologic impact of coronary artery dissections. Therefore, we studied the impact of coronary dissections on coronary flow velocity and outcome as well as their healing rate at 6-month follow-up balloon angioplasty. Of 297 patients who underwent balloon angioplasty, 225 underwent intracoronary Doppler measurements and 184 had Doppler and angiographic assessment at 6-month follow-up. Dissections were scored by an independent core lab (Cardialysis BV) and divided in 4 groups: mild (types A to B), moderate (type C), severe (D to F), and patients without dissections. Severe dissections (types D to F) were excluded from the analysis. Clinical, angiographic, and Doppler data were compared among the remaining 3 patient groups. From the 67 dissections detected after balloon angioplasty, only 3 (4.5%) remained unhealed at follow-up. Immediately after balloon angioplasty, the moderate dissection group was associated with a lower coronary flow velocity reserve than the patients with mild (2.16 +/- 0.60 vs 2.82 +/- 1.00, p = 0.037) or no dissections (2.16 +/- 0.60 vs 2.71 +/- 0.88, p = 0.046), respectively. In addition, higher recurrence of angina at 30 days was observed in the moderate group rather than in the mild group (5 [50%] vs 8 [16%], p = 0.0160) and in the patients without dissections (11 [12%], p = 0.007). After standard balloon angioplasty, the occurrence of unhealed dissections is a rare phenomenon. An impaired coronary flow reserve was observed after the development of nonocclusive type C dissections, which was associated with a worse short-term outcome.

Three-dimensional intravascular ultrasonic volumetric quantification of stent recoil and neointimal formation of two new generation tubular stents.

Currently, several different designs of coronary stents are available. However, only a few of the new generation stents have been investigated in large randomized trials. Mechanical behavior of first-generation stents (Palmaz-Schatz, Gianturco-Roubin) may not be applied to the new designs. We investigated the chronic mechanical behavior (recoil) of 2 stents recently approved by the Food and Drug Administration (MULTILINK and NIR). Forty-eight patients with single-stent implantation (23 MULTILINK and 25 NIR) were assessed by means of volumetric 3-dimensional intravascular ultrasound analysis after the procedure and at 6-month follow-up. In addition, volumetric assessment of neointimal formation was performed. No significant chronic stent recoil was detected in both groups (delta MULTILINK stent volume: +5.6+/-41 mm3 [p = NS] and delta NIR stent volume + 2.1+/-26 mm3 [p = NS]). A similar degree of neointimal formation at 6 months was observed between the 2 stents (MULTILINK 46+/-31.9 mm3 vs NIR 39.9+/-27.6 mm3, p = NS). In conclusion, these 2 second-generation tubular stents did not show chronic recoil and appeared to promote similar proliferative response after implantation in human coronary arteries.

The effect of 32P beta-radiotherapy on both vessel remodeling and neointimal hyperplasia after coronary balloon angioplasty and stenting: a three-dimensional intravascular ultrasound investigation.

Intracoronary radiation is a promising therapy to decrease restenosis after percutaneous intervention. The aim of this pilot study was to determine the mechanism of intracoronary beta-radiation after balloon angioplasty and stenting in a double-blind placebo-controlled randomized fashion. Twenty-six patients were randomized to either placebo (n = 6) or 3 doses (28, 35 and 42 Gy) of beta-radiation (n = 20) using the Guidant brachytherapy system (27 mm long 32P source wire). Of these, 21 patients underwent post-procedure and 6-month follow-up three-dimensional intravascular ultrasound (IVUS) assessment. Volumetric quantification was performed by means of a semi-automated contour detection system after an ECG-gated motorized pullback IVUS imaging and three-dimensional reconstruction. We compared the volumetric changes (Delta) of total vessel volume (TVV), plaque volume (PV) and lumen volume (LV) after 6 months between placebo (dummy wire) and irradiated patients. In addition, the volume of neointimal hyperplasia was quantified within the stented segments. There was an opposite behavior of TVV and LV change between placebo (DeltaTVV = -24 mm3 and DeltaLV = -42 mm3) and irradiated (DeltaTVV = +18 mm3 and (DeltaLV = +5 mm3) patients. The mean neointimal formation within the stented segment in the irradiated patients (n = 7) was 1.9 mm3 (1.5%). Our results suggest that beta-radiation affects vessel remodeling after percutaneous intervention and inhibit neointimal formation in stented patients.

Late stent malapposition occurring after intracoronary beta-irradiation detected by intravascular ultrasound.

We report a case of late stent malapposition occurring 6 months after intracoronary beta-irradiation detected by three-dimensional intravascular ultrasound, in spite of good apposition immediately after the procedure. Volumetric quantification revealed that stent volume remained unchanged, whereas total vessel volume increased by 13% after 6 months within the stent area. The increase of the vessel volume took place mainly in the proximal part of the stent, where the malapposition was located.

Compassionate use of intracoronary beta-irradiation for treatment of recurrent in-stent restenosis.

Recurrent in-stent restenosis after balloon angioplasty poses a serious management problem. Previously g-radiation has been shown to be effective in patients with in-stent restenosis. The aim of the study was to determine the feasibility and safety of b-radiation in patients with recurrent in-stent restenosis. From May 1997 to December 1998, 18 patients were treated with balloon angioplasty (n = 8) or laser (n = 10), followed by intracoronary b-radiation at a prescribed dose of 16 Gray at 2 mm from the source, for reference diameters by quantitative coronary angiography < 3.25 mm or 20 Gray for reference diameters > or =3.25 mm. Vessels treated were as follows: left anterior descending: (n = 5); circumflex: (n = 4); right coronary artery: (n = 6); saphenous vein graft: (n = 3). Average recurrence rate was 2.4 +/- 0.7 and the restenotic length was 16 +/- 7 mm. b-radiation was successfully delivered in all patients. Two patients presented complications related to laser debulking: a non-Q wave myocardial infarction in one and a re-angioplasty due to uncovered distal dissection in another. Geographical miss, defined as an area which has been injured but not covered by the radiation source, was demonstrated in 8 patients. Seventeen patients (94%) completed the 6-month angiographic follow-up. Restenosis (> 50% Diameter Stenosis) was observed in 9 patients (53%), leading to target lesion revascularization in 8 patients (47%). Six of the 9 restenoses were located in areas with geographical miss. Intracoronary b-radiation for recurrent in-stent restenosis appears to be a safe and feasible management strategy. However, the mismatch between injured and irradiated area may lead to failure of this therapy.

Long-term outcome of percutaneous transluminal coronary angioplasty and coronary bypass surgery for multivessel coronary artery disease.

We studied the short- and long-term outcomes of 97 patients treated with percutaneous transluminal coronary angioplasty (PTCA) and 72 patients treated with coronary artery bypass graft surgery (CABG) for multivessel coronary artery disease in a single hospital in 1989. Patients treated with CABG had a higher angina class, a higher incidence of diabetes mellitus and a greater extent of the disease. Complete revascularization was achieved in 61 patients (85%) with CABG and in 45 patients (46%) with PTCA (p < 0.001). Initial success of PTCA and CABG was obtained in 95% and 94% of the patients with PTCA and CABG, respectively. Actuarial survival rates at 5 years were similar (96% in the PTCA group; 94% in the CABG group). Fewer patients suffered from cardiac death or myocardial infarction in the CABG group than in the PTCA group, but this difference was not significant. The rate of survival free from death, myocardial infarction, CABG and repeat PTCA, was significantly higher in the CABG group than in the PTCA group (85% vs 48%; p < 0.001). These results suggest that CABG provides a favorable long-term outcome in patients with multivessel coronary artery disease and that PTCA provides a similar outcome in these patients when applied to suitable lesions, although more patients who undergo PTCA require repeat procedures.

Coronary stent implantation in a septal perforator artery: case report and review of the literature.

Septal perforator arteries play an important role in the blood supply of the anterior interventricular septum. Their intramyocardial course makes them inaccessible for coronary bypass revascularization. Although modern catheter-based techniques might be superior to coronary bypass grafting in offering the most complete revascularization in selected patient populations, a systematic review of the literature revealed a paucity of data regarding the outcome of these patients. The present report describes coronary stent implantation in a dominant septal perforator artery and the analysis of the anatomic relationship between the stent and the intraventricular septum using a new imaging technique, catheter-based intracardiac ultrasound.

Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation.

BACKGROUND: Cilostazol is an antiplatelet agent that increases the intracellular concentration of cyclic adenosine monophosphate by inhibiting phosphodiesterase III; it has been shown to reduce neointimal hyperplasia in animal balloon injury models. METHODS: One hundred thirty patients who underwent elective stenting (Palmaz-Schatz stent) were randomly assigned to cilostazol treatment 200 mg/d (n = 65) or to ticlopidine treatment 200 mg/d (n = 65). Angiographic follow-up was performed at 6 months, and clinical follow-up was continued up to 1 year. RESULTS: One sudden death and one myocardial infarction resulting from subacute occlusion were observed in the ticlopidine group. Drug adverse effects were observed in 3 patients in the cilostazol group, as opposed to 6 patients in the ticlopidine group. In the intention-to-treat analysis, 56 patients (61 lesions) in the cilostazol group and 58 patients (58 lesions) in the ticlopidine group were assessed with quantitative coronary angiography. Late loss in the cilostazol group was smaller (0.58+/-0.52 mm vs. 1.09+/-0.65 mm, P<.0001) than in the ticlopidine group. The restenosis rate was lower in the cilostazol group than in the ticlopidine group (16% vs. 33%, P = .044). The target vessel revascularization rate at 1 year was 23% in the cilostazol group and 42% in the ticlopidine group (P =.03). CONCLUSIONS: The results of this study suggest that cilostazol may be a safe medication that is effective in preventing restenosis after stent implantation.

Mid-term follow-up of coronary artery aneurysm after directional coronary atherectomy.

Coronary artery aneurysm (CAA) occurs in 6-12% of lesions after directional coronary atherectomy (DCA). The prognosis and the optimal treatment for DCA-related CAAs have not been well known. Therefore, we reviewed the clinical course of 214 consecutive patients with DCA-related CAAs who underwent DCA in our hospital. Follow-up coronary angiography 6 months after DCA was completed in 193 patients (212 lesions) and 14 lesions with CAAs (14 patients) were detected. We evaluated these 14 lesions by repeat coronary angiography at an average of 32 months after DCA in comparison with the adjacent reference vessel. Twelve of the 14 patients have been uneventful but 2 suffered from de novo angina due to new stenotic lesion unrelated to the DCA procedures. We compared the preprocedural angiographic characteristics and periprocedural parameters between the 14 lesions with CAAs[CAA(+)group] and the 198 without CAAs [CAA(-)group], but found no significant differences. Histological examination of specimens retrieved during atherectomy demonstrated that subintimal resection was more frequent in the CAA(+)group(57%) than the CAA(-)group(31%). The diameter of the aneurysm divided by the reference diameter was significantly larger at 6 months immediately after DCA(1.71 +/- 0.21 vs 1.31 +/- 0.18, p < 0.05) but did not change subsequently (1.68 +/- 0.23). Our retrospective analysis revealed a good mid-term (an average of 32 months) prognosis for CAAs found by routine follow-up coronary angiography and also demonstrated that the depth of resection was significantly associated with aneurysm formation.

Retrospective analysis of cerebral complications after coronary artery bypass grafting in elderly patients.

The present study retrospectively investigated cerebral complications of coronary artery bypass grafting in 205 consecutive patients aged 70 years or older, who underwent elective cardiopulmonary bypass from 1990 to 1997. Computed tomography of the brain and chest was done before surgery. Ten patients had so-called 'aortic no-touch surgery' and suffered no cerebral complications; the other 195 patients had conventional surgery. Adverse cerebral events occurred in 8.7%, including cerebral infarction (4.1%), diffuse encephalopathy (1.0%), convulsions (1.0%), transient disturbance of consciousness (1.0%), and severe loss of volition (1.5%). Multivariate analysis showed that only the detection of calcification of the ascending aorta was significantly associated with cerebral complications (p = 0.029). Total clamping tended to be superior to partial clamping for prevention of cerebrovascular accidents. The mortality rate was 7.3%. In-hospital death was related to age (p = 0.0062), cerebral complications (p = 0.0032), and a low left-ventricular function (p = 0.018). Therefore, chest computed tomography to assess the ascending aorta should be performed preoperatively. Modified techniques like aortic no-touch surgery or other therapies combined with coronary intervention may be needed in elderly patients with severe calcification of the ascending aorta.