12 research outputs found
Clinical evaluation of radioactive stents
Restenosis, the major problem after stent implantation, is caused by in-stent neointimal
hyperplasia. A number of metbods and techniques have been studied during the last
ten years to address tbis issue, but in-stent restenosis has remained at a rate of 15-25%
in most of tbe clinical trials. Several experimental and clinical trials showed that
brachytherapy, following a balloon angioplasty or stent implantation, reduced restenosis
by inhibiting neointimal hype
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
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
Preserved endothelium-dependent vasodilation in coronary segments previously treated with balloon angioplasty and intracoronary irradiation
BACKGROUND: Abnormal endothelium-dependent coronary vasomotion has been
reported after balloon angioplasty (BA), as well as after intracoronary
radiation. However, the long-term effect on coronary vasomotion is not
known. The aim of this study was to evaluate the long-term vasomotion of
coronary segments treated with BA and brachytherapy. METHODS AND RESULTS:
Patients with single de novo lesions treated either with BA followed by
intracoronary beta-irradiation (according to the Beta Energy Restenosis
Trial-1.5) or with BA alone were eligible. Of these groups, those patients
in stable condition who returned for 6-month angiographic follow-up formed
the study population (n=19, irradiated group and n=11, control group).
Endothelium-dependent coronary vasomotion was assessed by selective
infusion of serial doses of acetylcholine (ACh) proximally to the treated
area. Mean luminal diameter was calculated by quantitative coronary
angiography both in the treated area and in distal segments. Endothelial
dysfunction was defined as a vasoconstriction after the maximal dose of
ACh (10(-6) mol/L). Seventeen irradiated segments (89.5%) demonstrated
normal endothelial function. In contrast, 10 distal nonirradiated segments
(53%) and 5 control segments (45%) demonstrated endothelium-dependent
vasoconstriction (-19+/-17% and -9.0+/-5%, respectively). Mean percentage
of change in mean luminal diameter after ACh was significantly higher in
irradiated segments (P=0.01). CONCLUSIONS: Endothelium-dependent
vasomotion of coronary segments treated with BA followed by beta-radiation
is restored in the majority of stabl
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 beta 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 disse
The temporal pattern of immune and inflammatory proteins prior to a recurrent coronary event in post-acute coronary syndrome patients
Purpose: We assessed the temporal pattern of 29 immune and inflammatory proteins in post-acute
coronary syndrome (ACS) patients, prior to the development of recurrent ACS.
Methods: High-frequency blood sampling was performed in 844 patients admitted for ACS during
one-year follow-up. We conducted a case-control study on the 45 patients who experienced reACS
(cases) and two matched event-free patients (controls) per case. Olink Proteomics’ immunoassay was
used to obtain serum levels of the 29 proteins, expressed in an arbitrary unit on the log2-scale
(Normalized Protein eXpression, NPX). Linear mixed-effects models were applied to examine the temporal pattern of the proteins, and to illustrate differences between cases and controls.
Results: Mean age was 66 ± 12 years and 80% were men. Cases and controls had similar baseline clinical
characteristics. During the first 30 days, and after multiple testing correction, cases had significantly higher
serum levels of CXCL1 (difference of 1.00 NPX, p ¼ 0.002), CD84 (difference of 0.64 NPX, p ¼ 0.002) and
TNFRSF10A (difference of 0.41 NPX, p < 0.001) than controls. After 30 days, serum levels of all 29 proteins
were similar in cases and controls. In particular, no increase was observed prior to reACS.
Conclusions: Among 29 immune and inflammatory proteins, CXCL1, CD84 and TNFRSF10A were associated with early reACS after initial ACS-admission
The temporal pattern of immune and inflammatory proteins prior to a recurrent coronary event in post-acute coronary syndrome patients
Purpose: We assessed the temporal pattern of 29 immune and inflammatory proteins in post-acute coronary syndrome (ACS) patients, prior to the development of recurrent ACS. Methods: High-frequency blood sampling was performed in 844 patients admitted for ACS during one-year follow-up. We conducted a case-control study on the 45 patients who experienced reACS (cases) and two matched event-free patients (controls) per case. Olink Proteomics’ immunoassay was used to obtain serum levels of the 29 proteins, expressed in an arbitrary unit on the log2-scale (Normalized Protein eXpression, NPX). Linear mixed-effects models were applied to examine the temporal pattern of the proteins, and to illustrate differences between cases and controls. Results: Mean age was 66 ± 12 years and 80% were men. Cases and controls had similar baseline clinical characteristics. During the first 30 days, and after multiple testing correction, cases had significantly higher serum levels of CXCL1 (difference of 1.00 NPX, p = 0.002), CD84 (difference of 0.64 NPX, p = 0.002) and TNFRSF10A (difference of 0.41 NPX, p < 0.001) than controls. After 30 days, serum levels of all 29 proteins were similar in cases and controls. In particular, no increase was observed prior to reACS. Conclusions: Among 29 immune and inflammatory proteins, CXCL1, CD84 and TNFRSF10A were associated with early reACS after initial ACS-admission
Cohort profile of BIOMArCS: The BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands
__Purpose:__ Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'.
__Participants:__ BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor.
__Methods and analysis:__ We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-Term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for nonfatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS
Geometric vascular remodeling after balloon angioplasty and beta-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
beta-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, beta-particle-emitting radioactive stents
decrease neointimal hyperplasia by inhibiting smooth muscle cell
proliferation. METHODS AND RESULTS: The radioisotope (32)P, a
beta-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
microCi. 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 (n=12), the right coronary artery (n=8), or the
left circumflex coronary artery (n=6). Five patients received additional,
nonradioactive stents. Treated lesion lengths were 13+/-4 mm, with a
reference diameter of 2.93+/-0. 47 mm. Minimum lumen diameter increased
from 0.87+/-0.28 mm preprocedure to 2.84+/-0.35 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
1.85+/-0.69 mm, which resulted in a late loss of 0.99+/-0. 59 mm and a
late loss index of 0.53+/-0.35. 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 microCi is safe and feasible