Biomedical subjects

Paul Wexberg

Publications and source records attributed to Paul Wexberg.

13 recordsLinked to original sources

PubMed2004

Vascular remodeling in atherosclerotic femoral arteries: three-dimensional US analysis.

PURPOSE: To investigate the various modes of vascular remodeling of atherosclerotic femoral arteries and determine the associations between type of arterial remodeling and clinical data (age, sex, and medical history) and inflammatory parameters. MATERIALS AND METHODS: Intravascular ultrasonography (US) of the femoral arteries was performed in 50 patients with clinical symptoms of peripheral vascular disease. To determine the arterial remodeling mode (expansive remodeling [ER], involving compensatory enlargement of the artery, or constrictive remodeling [CR], involving vessel constriction during progression of atherosclerosis), the cross-sectional areas (CSAs) of the external elastic membrane (EEM), lumen, and plaque-plus-media were measured every 0.1 mm by using three-dimensional reconstruction. Clinical, laboratory, and intravascular US data were compared in the different remodeling groups (dominant ER, dominant CR, or mixed remodeling) by using analysis of variance supplemented by Tukey-Kramer tests. Multivariate analysis was performed to test independent variables predicting dominant ER. RESULTS: Intravascular US revealed the parallel existence of ER and CR in all patients: Increases and decreases in EEM in response to plaque growth could be observed within the same artery. ER dominated in 13 (26%) patients, and CR dominated in 11 (22%) patients: At least 80% of EEM CSAs were higher or lower than the mean of the EEM CSAs of the segments proximal and distal to the lesion. Patients with dominant ER had higher levels of serum C-reactive protein (CRP) compared with levels in patients with dominant CR and patients with mixed remodeling (1.62 mg/dL +/- 2.05 [standard deviation] vs 0.19 mg/dL +/- 0.33 and 0.21 mg/dL +/- 0.39, respectively, P < .005). Multivariate analysis revealed high CRP level to be a significant independent predictor for dominant ER (P < .01). CONCLUSION: The parallel existence of ER and CR was found in all patients with peripheral atherosclerosis, with a dominance of vessel expansion in 26% of patients. Higher plasma CRP level was associated with dominant ER.

Aged↗

PubMed2004

Adventitial response to intravascular brachytherapy in a rabbit model of restenosis.

BACKGROUND: The incidence of late major adverse cardiac events (MACE) after coronary brachytherapy is higher than in controls. Because expansive remodeling has been shown to correlate with poor clinical outcome after vascular interventions, we studied adventitial changes after intravascular irradiation in a rabbit model. METHODS: Twenty normolipidemic rabbits underwent balloon injury in both external iliac arteries. One artery was assigned for subsequent irradiation with a 90Y source (15 Gy or 30 Gy at 0.5 mm in the vessel wall). After four weeks morphometric measurements were made and cell density and collagen amount determined. Staining for Ki67 identified proliferating cells; apoptotic cells were identified by TUNEL staining. Proliferative and apoptotic indices were calculated as the number of respective positive cells/total cell count x100. RESULTS: The neointimal area decreased to 0.27 +/- 0.3 mm2 after irradiation compared with 0.55 +/- 0.2 mm2 in controls (p=0.007), whereas adventitial area increased from 0.62 +/- 0.3 mm2 to 0.87 +/- 0.3 mm2 (p=0.02). Irradiation reduced both the proliferative (0.95 +/- 2.6 vs. 3.73 +/- 4.7, p=0.026) and apoptotic (0.006 +/- 0.02 vs. 0.107 +/- 0.2, p=0.03) indices in the neointima, but not in the other arterial-wall layers. Collagen amount and arterial remodeling did not differ between the groups. There was no difference between 15 and 30 Gy in any of the parameters, although adventitial thickening was more pronounced in the high-dose group. CONCLUSIONS: In normolipidemic rabbits, intravascular beta-irradiation after balloon angioplasty is associated with an increase in neoadventitia and a reduction of neointima. It is conceivable that this phenomenon may contribute to the increased incidence of late MACE after vascular brachytherapy.

Angioplasty, Balloon↗

PubMed2004

Short- and long-term clinical outcome after various stent implantation: overview of the results of uni- and multicenter stent registries.

The present study reports the results of the short- and long-term outcomes of prospective uni- and multicenter stent registries: Palmaz-Schatz (n = 140 patients), Ave-Micro and GFX (n = 280), Multilink Duet (n = 340), Multilink Tetra (n = 192), and Carbo (n = 140) Stent Registries, as well as the predictors and angiographic cutoff points predicting major adverse cardiac events (MACE) after different stent implantations. Significant decrease in subacute stent thrombosis (from 2.9% to 0) and MACE (from 35% to 8.3%) occurred as the improved stents, optimized stent implantation technique, and new postintervention drug therapy were introduced. The changes of angiographic cutoff values (postintervention minimal lumen diameter and preintervention reference diameter: from 2.9 and 3.1 mm for Palmaz-Schatz to 2.5 and 2.8 mm for Multilink Duet, Multilink Tetra, and Carbo stents) and clinical and angiographic factors predicting MACE indicated the change of traditional restenosis paradigm and that progress in clinical practice might be able to counterbalance unfavorable lesion and intervention-related characteristics.

Coronary Angiography↗

PubMed2004

Quality assurance in intracoronary brachytherapy. Recommendations for determining the planning target length to avoid geographic miss.

BACKGROUND AND PURPOSE: A new method of assessing geographic miss (GM) in endovascular brachytherapy (EVBT) is applied to evaluate the quality of intracoronary brachytherapy treatments, retrospectively. Based on the Vienna experience, recommendations for adequate safety margins are derived to avoid GM. PATIENTS AND METHODS: Evaluation is done on 136 vessels of 128 consecutive patients treated between October 1999 and July 2001. The quality of EVBT is assessed using the concept and terminology of the EVA GEC ESTRO task group. Evaluation of GM and/or safety margin is performed by comparing the outermost interventions with the reference isodose length (RIL) of the applied delivering devices on recorded compact disk (CD) angiograms. The RIL is defined as the length of the vessel segment, which receives at least 90% of the reference dose at the reference depth (=1 mm within the vessel). GM is defined as injured vessel segments, which receive a dose lower than 90% of reference dose. Measurements of intervention length (IL) and active source length (ASL) are performed with respect to anatomical landmarks within the vessel in the region of interest (e.g. stent edges), and by using the nominal length of the devices (balloons, sources) as a reference scale. The edges of RIL are determined by subtracting the length of the dose-fall-off zone (specific to the applied delivery devices: (192)Ir 4.5 mm, (90)Sr 2.5 mm, (32)P 2.0 mm) from the edges of ASL. RESULTS: The described method to assess GM is applicable to 128 vessels (94%). GM is found in 23% of proximal edges and 20% of distal edges. 95% of all GM are observed if the total margin (proximal+distal margin) between RIL and IL is shorter than 10.5 mm. CONCLUSIONS: GM in intracoronary brachytherapy can be widely avoided by adding an appropriate safety margin to the IL (5-6 mm each edge in this study) in order to determine the necessary RIL for a treatment.

Brachytherapy↗

PubMed2004

Estimation of doses to personnel and patients during endovascular brachytherapy applications.

In the last few years coronary endovascular brachytherapy using gamma- and beta-emitting radionuclides has been established as a standard treatment procedure to prevent restenosis after percutaneous coronary interventions. Direct measurements and calculations were made to determine personnel doses and organ doses of patients due to gamma rays of 192Ir and beta rays of 90Sr/90Y and 32P sources. In general, our results show that the dose levels are low compared with the X-ray exposure from angiography. The dose rate from bremsstrahlung at 1 m distance from a device containing a 90Sr/90Y source of 2.3 GBq is 4 micro Sv h(-1). The skin dose from beta rays during source transfer into and from the patient was estimated with the directional dose equivalent H'(0.07) of 10 micro Sv at 1 m distance from the catheter. By maintaining safe distances, the dose levels can be kept well within annual dose limits.

Beta Particles↗

PubMed2003

Effects of radial stretch on target lesion revascularization after percutaneous coronary intervention: an intravascular ultrasound study.

OBJECTIVE: To analyze possible associations between radial stretch during coronary angioplasty and the incidence of target lesion revascularization (TLR). PATIENTS AND METHODS: Intravascular ultrasound images were obtained before and after revascularization in 182 native coronary lesions. The quantitative intravascular ultrasound parameters (external elastic membrane cross-sectional area [EEM-A], lumen areas [LA], plaque area [PA], calculated as EEM-A-LA, and changes between pre- and postinterventional LA [DLA], EEM-A [DEEM-A] and PA [DPA]) were correlated with the incidence of TLR. RESULTS: TLR was performed in 60 (33%) patients, while 122 (67%) patients remained event free. Postinterventional PA remained significantly larger in the TLR group than in the event-free group (9.2 +/- 3.3 mm2 versus 7.9 +/- 3.3 mm2; P=0.02). The radial stretch during intervention, expressed as DEEM-A, and the balloon to artery ratio was significantly larger in the TLR group (DEEM-A: 1.9 +/- 2.1 mm2 versus 1.3 +/- 2.0 mm2; P=0.03; balloon to artery ratio: 1.3 +/- 0.2 versus 1.0 +/- 0.5; P=0.04). Multivariate analysis revealed DEEM-A (P=0.01), DPA (P=0.03), diabetes (P=0.001, odds ratio 5.2, 95% CI 4.9 to 6.5) and adaptive remodelling (P<0.001, odds ratio 4.1, 95% CI 3.5 to 6.4) as independent predictors for TLR. CONCLUSION: Whereas patients in whom lumen gain is achieved primarily by plaque reduction with less wall stretch tend to remain event free, patients with significant radial stretch (ie, less reduction of the PA, but a radial outward shift of the plaque mass) experience a higher incidence of TLR.

Aged↗

PubMed2003

Inhibition of interleukin-1beta convertase is associated with decrease of neointimal hyperplasia after coronary artery stenting in pigs.

Inhibition of IL-1beta convertase has been shown to decrease inflammation and apoptosis, which are features of the neointimal development after vascular interventions. The aim of our study was to reduce neointimal proliferation after stenting of the porcine coronary artery, using the irreversible IL-1beta convertase and caspase-1 inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethyl-ketone (Ac-YVAD-cmk). Before coronary stent implantation, 8 pigs received an intracoronary infusion of 50 mg Ac-YVAD-cmk into the left coronary artery (group 1, n = 8), while 8 animals served as untreated controls (group 2). After 4 weeks, coronary angiography and intracoronary ultrasound (IVUS) with 3D measurements were performed. IVUS revealed a smaller in-stent intimal volume (27.3 +/- 11.6 vs. 75.8 +/- 18.4 mm3, p < 0.005) and a decreased maximal percentage area stenosis (36.1 +/- 8.5 vs. 69.0 +/- 8.2%, p < 0.001) in group 1 vs. group 2. A smaller maximal neointimal thickness (0.63 +/- 0.28 vs. 1.75 +/- 0.94 mm, p < 0.005) and a decreased maximal neointimal area (2.14 +/- 1.29 vs. 5.03 +/- 1.92 mm2, p < 0.005), assessed by computerized planimetry, were found in group 1 vs. group 2. Lower apoptotic indices of the neointimal cells were observed in the treated animals (3.0 vs. 13.4% of total intimal cells, p < 0.05). The coronary arterial tissue IL-1beta level was significantly decreased in the animals treated with Ac-YVAD-cmk (0.254 +/- 0.162 vs. 0.463 +/- 0.307 pg/mg protein, p < 0.05), and exhibited a positive linear correlation (r = 0.581, p = 0.013) with the in-stent plaque volume. In conclusion, intracoronary administration of Ac-YVAD-cmk before coronary artery stenting results in significantly decreased neointimal hyperplasia due to the inhibition of local IL-1beta production and decreased neointimal apoptosis.

Amino Acid Chloromethyl Ketones↗

PubMed2002

Geographical miss during intracoronary irradiation: impact on restenosis and determination of required safety margin length.

OBJECTIVE: The goal of this study was to evaluate the incidence and effects of underdosage of injured segments during intracoronary irradiation and to define the minimal length of safety margin required to avoid mismatched source placement. BACKGROUND: Underdosage of injured segments due to misplacement of active source has been suggested as the underlying mechanism for the occurrence of edge restenosis. METHODS: Baseline angiograms of 112 vessels in 109 patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation ((192)Ir: Checkmate, Cordis, Miami, Florida; (32)P: Gallileo, Guidant, Houston, Texas; (90)Sr/Y: Beta-Cath, Novoste, Norcross, Georgia) were analyzed. The distances between the outermost injury and outermost end of "reference isodose length" (RIL), defined as a segment with >/=90% of reference dose at 1 mm vessel wall depth, were measured. "Safety margin" was defined as the distance between the outermost injury and outermost end of the RIL, "geographical miss" (GM) as a complete injured segment not being covered by the RIL, and "restenosis" as the percent diameter stenosis >50%. RESULTS: Baseline angiographic analysis was performed for 224 edges in 112 vessels. Geographical miss was found in 46 (20.6%) edges. The incidence of target lesion restenosis within the 78 vessels with available follow-up was 43.3% for patients with GM versus 14.9% for patients with no GM (p = 0.005). Analysis of various injured segments exposed highest restenosis rates in injured segments with negligible irradiation (27.8%) in comparison with injured segments with dose fall-off (16.7%) or injured segments with full-dose irradiation (7.7%) (p = 0.006). Receiver operating curve analysis revealed a safety margin of 10 mm required per vessel (i.e., 5-mm safety margin/edge) to achieve 95% specificity of GM. CONCLUSIONS: Geographical miss is associated with a higher incidence of restenosis at the corresponding edges. Restenosis was more pronounced in injured segments with negligible irradiation than in injured segments at the dose fall-off zones. We recommend a safety margin of 10 mm per vessel to minimize GM.

Beta Particles↗

PubMed2002

Vascular morphometric changes after radioactive stent implantation: a dose-response analysis.

OBJECTIVES: The goal of this study was to evaluate the dose-dependency of morphometric changes in the coronary arterial wall after radioactive stenting. BACKGROUND: Radioactive stents have been found to reduce intrastent intimal hyperplasia (IIH) but lead to a characteristic type of restenosis occurring predominantly at the stent edges. METHODS: Fifteen patients underwent intravascular ultrasound (IVUS) examination after implantation of a P-32 radioactive stent and at the six-month follow-up. The post-stent IVUS measurements on seven predefined locations of each lesion were subjected to a computer algorithm for the development of dose-volume histograms (DVH). Thus, we derived the radiation doses delivered to at least 10% and 90% of the adventitia (DV10, DV90). The IIH and vascular remodeling at follow-up were correlated with the doses in each segment. RESULTS: The IIH was most pronounced at the stent edges and lowest in the stent-body, whereas we detected a significant expansive remodeling within the stent body. The delivered doses correlated with a decreased IIH (r = 0.52, p < 0.001 for DV10 and r = 0.62, p < 0.001 for DV90) and with expansive remodeling (r = 0.48, p = 0.009 for DV10 and r = 0.50, p = 0.006 for DV90). A DV10 >90 Gy or a DV90 >15 Gy reduced IIH and induced expansive remodeling. Plaque growth was not reduced by radioactive stents. CONCLUSIONS: The DVH analysis reveals a dose-dependent increase of external elastic lamina area behind radioactive stents, whereas plaque growth is not reduced but inverted into an outward direction from the stent. A DV10 >90 Gy or a DV90 >15 Gy results in a beneficial long-term outcome after radioactive stenting.

Arteries↗

PubMed2002

Determination and application of the reference isodose length (RIL) for commercial endovascular brachytherapy devices.

BACKGROUND AND PURPOSE: During the last years endovascular brachytherapy has been established as a new field in radiotherapy. In a recent recommendation of the EndoVAscular, Groupe Européen de Curiethérapie, European Society for Therapeutic Radiation Oncology, Working Group the reference isodose length (RIL) has been introduced as a central parameter for treatment planning. It is defined as the vessel length at the reference depth enclosed by the 90% isodose. The dose is normalized to 100% at the reference depth (i.e. lumen radius plus 1 mm into the vessel wall) at the central plane. In order to avoid a geographic miss the clinical target length has to be encompassed by the RIL. MATERIAL AND METHODS: RILs are determined by Monte Carlo calculations and GafChromic film dosimetry for three endovascular brachytherapy devices currently in clinical use (192Ir seed ribbon, 32P wire source, 90Sr seed train). For all measurements, phantoms and devices the sensitive layer of GafChromic film is located in a plane at 2+/-0.1 mm parallel to the axis of the source delivery catheter. The EGSnrc code system is applied to calculate the dose profile at 2 and 3 mm distance from the source axis. RESULTS: For the ten seed 192Ir source calculated RIL at 2 mm radial distance is 30.2 mm whereas the measured RIL is 33.5 mm. In case of a 20 mm 32P wire source with two steps the calculated RIL of 36.6 mm shows excellent agreement compared with the measured value of 36.2 mm. The calculated RIL of a 40 mm 90Sr seed train was 35.8 mm compared to a measured value of 34.8 mm. CONCLUSION: As a compromise between calculated and measured RIL values at 2 and 3 mm radial distances we propose to use a RIL of 30 mm for the 192Ir ten seed ribbon, 36 mm for the32P wire source with two steps and 35 mm for the 40 mm 90Sr seed train. These parameter values can be used to define the maximum intervention length for endovascular sources.

Beta Particles↗

PubMed2002

Case-based distance measurements for the selection of controls in case-matched studies: application in coronary interventions.

In case-based studies, controls are retrospectively assigned to patients in order to permit a statistical evaluation of the study results through a comparison of the main outcome measures for the patient and retrieved control groups. Inappropriate selection of the controls by using false retrieval parameters or a false algorithm might lead to an incorrect data analysis and a false interpretation of the results. The main hypothesis of the presented study was that, if the matching baseline parameters were at least nearly perfectly selected, then the outcomes of the matched pairs should be similar, or no significant differences in study outcome should be observed between the patients and the matched controls. In the present study, the case-based domain was created from 1566 patients who had undergone intracoronary stent implantation. Uni- and multivariate logistic regression analysis determined nine significant predictors (matching variables) for the occurrence of major adverse cardiac events. An additional 425 consecutive patients undergoing intracoronary stent implantation were then matched with all the potential controls from the database by calculating the individual distance between the patient and the matched control on the basis of the elaborated retrieval algorithm. To test the matching hypothesis, different distance measurements, and an altered outcome and retrieval process were examined. With "flexible" distance measurements, the mean distance between the patients and the first matched controls was 1.31. The major adverse cardiac events were compared in the patient and matched control groups. The best sensitivity and specificity values of the matching system could be achieved in matched pairs with the distance < or =3.00 (95.1% of all patients). On the further stepwise exclusion of the matched pairs exhibiting a distance greater than 2 and 1, then the number of "matchable" controls and the specificity of our matching concept decreased considerably. When the short- or mid-term outcome was compared by using the long-term follow-up matching parameters, no correlation could be found between the treated subjects and controls, indicating that for the other study, main measures of other appropriate parameters must be selected, and demonstrating the importance of the outcome-oriented selection of the retrieval parameters. Furthermore, the outcome measures of the patients and randomly (non-systematically) selected controls did not correlate, revealing the impossibility of drawing correct study conclusions from a non-matched, randomly assigned pairs. In conclusion, the sensitivity and specificity of the matching program, and the study conclusions depend on the appropriately predefined matching parameters and retrieval algorithm.

Algorithms↗

PubMed2002

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1.

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.

Adult↗

PubMed2002

Mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients.

BACKGROUND: Diabetic patients show an increased incidence of restenosis after coronary angioplasty than non-diabetic patients. This may be because of differences in the mechanism of lumen gain during coronary revascularization in this population cohort. DESIGN: This study analyses the mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients with intravascular ultrasound (IVUS). METHODS: IVUS images were obtained prior to and after revascularization in 26 diabetic and 97 non-diabetic patients. The external elastic membrane cross-sectional area (EEM) and lumen cross-sectional area (LA) were measured. Plaque area (PA) was calculated as EEM minus LA. Differences between pre- and post-LA (deltaLA), EEM (deltaEEM) and PA (deltaPA) were calculated. RESULTS: Pre-interventional PA (diabetic patients: 12.4 +/- 4.4 mm2 compared with non-diabetic patients: 10.7 +/- 3.6 mm2, = 0.04) and pre-interventional EEM (15.5 +/- 4.4 mm2 compared with 13.6 +/- 3.7 mm2 respectively, P = 0.02) were larger in the diabetic group. Postinterventional PA (10.2 +/- 3.2 mm2 compared with 8.0 +/- 3.4 mm2, P = 0.004) was also larger and postinterventional LA (6.3 +/- 2.2 mm2 compared with 7.4 +/- 2.4 mm2 = 0.04), deltaEEM (0.9 +/- 1.8 mm2 compared with 1.8 +/- 1.8 mm2 P = 0.04) and deltaLA (3.1 +/- 1.6 mm2 compared with 4.2 +/- 2.2 mm2, P = 0.03) were smaller in the diabetic group. The diabetic group exhibited longer lesion lengths (P = 0.04) and a higher inflation pressure was used during revascularization in this patient cohort (P = 0.02). CONCLUSION: Diabetic patients have less reduction of PA during revascularization and because the vessel wall cannot be stretched outwards despite higher inflation pressure, postinterventional LA remains smaller than in the non-diabetic population cohort. This might be a rudiment for consideration of different treatment strategies such as cutting balloon or atherectomy prior to stenting in this population group in order to achieve better procedural outcome.

Aged↗