Giessen, W.J. van der

Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes (Article)

2012-01-01T00:00:00Z

Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated coronary artery disease (CAD) development is difficult in patients. Therefore, we investigated coronary conduit and small artery function in a preatherosclerotic DM porcine model with type 2 characteristics. Streptozotocin-induced DM pigs on a saturated fat/cholesterol (SFC) diet (SFC + DM) were compared with control pigs on SFC and standard (control) diets. SFC + DM pigs showed DM-associated metabolic alterations and early atherosclerosis development in the aorta. Endothelium-dependent vasodilation to bradykinin (BK), with or without blockade of nitric oxide (NO) synthase, endothelium-independent vasodilation to an exogenous NO-donor (S-nitroso-N-acetylpenicillamine), and vasoconstriction to endothelin (ET)-1 with blockade of receptor subtypes, were assessed in vitro. Small coronary arteries, but not conduit vessels, showed functional alterations including impaired BK-induced vasodilatation due to loss of NO (P < 0.01 vs. SFC and control) and reduced vasoconstriction to ET-1 (P < 0.01 vs. SFC and control), due to a decreased ETa receptor dominance. Other vasomotor responses were unaltered. In conclusion, this model demonstrates specific coronary microvascular alterations with regard to NO and ET-1 systems in the process of early atherosclerosis in DM. In particular, the altered ET-1 system correlated with hyperglycemia in atherogenic conditions, emphasizing the importance of this system in DM-associated CAD development.

A proinflammatory monocyte response is associated with myocardial injury and impaired functional outcome in patients with ST-segment elevation myocardial infarction: Monocytes and myocardial infarction (Article)

2012-01-01T00:00:00Z

Background: In patients with ST-segment elevation myocardial infarction (STEMI), the importance of a well-balanced inflammatory reaction has been recognized for years. Monocytes play essential roles in regulating inflammation. Hence, we investigated the association between inflammatory characteristics of monocytes and myocardial injury and functional outcome in patients with STEMI. Methods: Using flow cytometry, the levels of classical (CD14++CD62L+) and nonclassical (CD14+CD62L-) monocytes were analyzed in peripheral blood in 58 patients with STEMI at a median of 5 days (4-6 days) after primary percutaneous coronary intervention. In addition, the monocytic expression of several surface molecules and formation of monocyte-platelet complexes were measured. All patients underwent cardiovascular magnetic resonance imaging at baseline and 4-month follow-up. Results: At baseline, patients with high levels of classical monocytes had impaired left ventricular (LV) ejection fraction (P =.002), larger infarct size (P =.001), and, often, presence of microvascular obstruction (P =.003). At follow-up, high levels of classical monocytes were negatively associated with the regional systolic LV function independent of the transmural extent of infarction. In contrast, positive associations for the levels of nonclassical monocytes were observed. Finally, up-regulation of macrophage 1 by blood monocytes and increased formation of monocyte-platelet complexes were associated with enhanced myocardial injury at baseline and impaired LV function at follow-up. Conclusions: This study shows an association between a proinflammatory monocyte response, characterized by high levels of classical monocytes, and severe myocardial injury and poor functional outcome after STEMI. Future studies are required to investigate the biologic nature of this association and therapeutic implications.

Long-term tissue coverage of a biodegradable polylactide polymer-coated biolimus-eluting stent: Comparative sequential assessment with optical coherence tomography until complete resorption of the polymer (Article)

2011-11-01T00:00:00Z

Background: Biolimus-eluting stents (BESs) with a biodegradable polymer in abluminal coating achieve more complete coverage at 9 months compared with sirolimus-eluting stents (SESs) with a durable polymer, as assessed by optical coherence tomography (OCT). Whether this advantage persists or augments after complete resorption of the polymer (>12 months) is unknown. Methods: The LEADERS trial compared the performance of BES with that of SES. Patients were randomly allocated to a sequential angiographic follow-up, including OCT in selected sites, at 9 and 24 months. Struts coverage was compared using Bayesian hierarchical models as the primary outcome for the OCT substudy. Results: Fifty-six patients (26 BES, 30 SES) were enrolled in the OCT substudy. Twenty-one patients (10 BES, 11 SES) agreed to perform a second OCT follow-up at 24 months. Eleven lesions and 12 stents were analyzed sequentially in the BES group (2,455 struts at 9 months, 2,131 struts at 24 months) and 11 lesions and 18 stents in the SES group (3,421 struts at 9 months, 4,170 struts at 24 months). The previously reported advantage of BES over SES in terms of better strut coverage at 9 months was followed by improvement in coverage of the SES, resulting in identical coverage in both BES and SES at 24 months: 1.5% versus 1.8% uncovered struts, difference -0.2%, 95% credibility interval, -3.2% to 2.6%, P =.84. Conclusions: More complete strut coverage of BES as compared with SES at 9 months was followed by improvement of coverage in SES between 9 and 24 months and a similar long-term coverage in both stent types at 24 months.

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: An optical coherence tomography substudy from the RESOLUTE All Comers trial (Article)

2011-10-01T00:00:00Z

Aim s To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an 'all-comers population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. Methods and resultsPatients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8, P 0.378), and 216 and 161 malapposed struts (1.8 and 1.4, P 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 m in ZES and 142 ± 113 m in EES (P 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7) or other areasvolumetric parameters were found between ZES and EES, respectively.ConclusionNo significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Evaluating the 'all-comers' design: A comparison of participants in two 'all-comers' PCI trials with non-participants (Article)

2011-09-01T00:00:00Z

Aims We aimed to asses the generalizability of two 'all-comers' randomized clinical trials (AC-RCTs) in patients undergoing percutaneous coronary intervention (PCI). Methods and resultsRecently two large AC-RCTs comparing drug-eluting stents were performed in our institution (LEADERS and RESOLUTE-III). During the inclusion period of these trials 1242 consecutive PCI patients were treated of whom 579 (48) were actually included. The most important reasons for non-participation were inability to provide informed consent (33.5), refused to participate (19), or patient met one of the other exclusion criteria (26.9). Trial participants more frequently had stable angina (42.5 vs. 34.4) and less frequently acute myocardial infarction as indication for PCI (31.4 vs. 42.4) than non-participants. Hypertension (52.8 vs. 49.1) and hypercholesterolaemia (56.3 vs. 49.1) were seen more frequently in trial participants; heart failure was less common (2.1 vs. 4.4). A significant difference in 30-day mortality was observed between AC-RCT participants and non-participants [0.7 vs. 4.5 events; adjusted hazard ratio (aHR) 0.18 and 95 confidence interval (CI) 0.060.52]. One-year mortality was also lower (3.1 vs. 6.9 events; aHR: 0.51 and 95 CI: 0.290.91, but 1-year mortality in 48 h survivors was similar (3.1 vs. 4.2 events; aHR: 0.74 and 95 CI: 0.411.34). Conclusion Applying the all-comers design did not result in inclusion of all consecutive patients, as only half of the target population was enrolled. It should be noted, however, that this design included more patients than observed in classical RCTs. AC-RCT participants and non-participants were different in terms of baseline characteristics and outcome.

Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs (Article)

2011-07-14T00:00:00Z

Background: Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet.Methods: Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study.Results: Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p < 0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p < 0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p < 0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p < 0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p < 0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R2= 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p < 0.05) in UF (571 ± 95) pigs.Conclusion: Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs.

Randomized comparison of the magnetic navigation system vs. standard wires in the treatment of bifurcations (Article)

2011-06-01T00:00:00Z

AimsRandomly compare the magnetic navigation system (MNS) to standard guidewire techniques in managing bifurcating lesions.Methods and resultsThirty-one consecutive patients with bifurcating lesions were randomized to cross the bifurcating vessels prior to treatment and thereafter the struts of deployed stents with either magnetic or standard guidewires. Crossing success, crossing/fluoroscopy times, and contrast media usage were directly compared. Similar times were noted in both the magnetic wire crossings (median, IQR; 68 s, 45138 s vs. 59 s, 32133 s) and fluoroscopic times (median, IQR; 62 s, 44135 s vs. 55 s, 27133 s) when compared with standard conventional wires passage through the deployed struts. The MNS successful crossings were 30/31 (96.8) compared with 28/31 (90.0) observed with the standard wires. Two previously failed standard wire cases were successfully crossed with magnetic guidewires.ConclusionIn contemporary stented bifurcations, the MNS achieved equivalent crossing/fluoroscopy times through deployed stents struts and may be useful in salvaging failed standard wire cases.

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

2011-06-01T00:00:00Z

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 (mm2) 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.

Value of the SYNTAX score in patients treated by primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: The MI SYNTAXscore study (Article)

2011-04-01T00:00:00Z

Aims: The aims of this study were to evaluate the SYNTAX score (SXscore) calculated at 2 stages during a primary percutaneous intervention (PPCI), that is, SXscore I (diagnostic) and SXscore II (postwiring), and assess its additional value to standard clinical risk scores in acute myocardial infarction. Methods and Results: SXscores I and II were applied to 736 consecutive acute ST-elevation myocardial infarction patients referred for PPCI between November 2006 and February 2008. SXscore changed significantly before (I: 16, interquartile range 9.5-23) and after wiring (II: 11, interquartile range 6-19), P < .001. Kaplan-Meier methods were used to compare the primary end point major adverse coronary events (MACE; composite of repeat MI, target vessel revascularization [TVR], and mortality) and secondary end point mortality at 1.5 years in tertiles of SXscore I and SXscore II. Major adverse coronary event was highest in the higher SXscore I tertile (11% vs 15% vs 23%, log-rank <0.01), driven primarily by increased rate of mortality (9% vs 11% vs 17%, log-rank 0.02). Major adverse coronary event was also highest in SXscore II tertile, by a combination of increased mortality and also TVR (TVR rate 2% vs 3% vs 9%, log-rank <0.01). Predictive Cox regression models for mortality and MACE were significantly and similarly improved by the addition of either SXscore I or SXscore II (hazard ratio 1.63, 95% CI 1.18-2.26, P < .01 for MACE) with respective c indices of 0.61 and 0.63 for MACE and 0.60 and 0.61 for mortality. Conclusions: SXscore during PPCI is a useful tool that provides additional risk stratification to known risk factors of long-term mortality and MACE in patients with ST-elevation myocardial infarction.

Late outcome after intracoronary beta radiation brachytherapy: A matched-propensity controlled ten-year follow-up study (Article)

2011-01-01T00:00:00Z

Aims: Increased major adverse cardiac events (MACE) beyond six months after intracoronary β radiation brachytherapy (IRBT) are a major concern. The aim of this study was to evaluate the 10-year clinical outcome after IRBT. Methods and results: From 1997 to 2002, 301 consecutive patients treated with IRBT were included prospectively, whereafter 602 control patients treated with conventional percutaneous coronary intervention (PCI) were matched by propensity score methodology. MACE was defined as all-cause death, any myocardial infarction or any revascularisation. Median follow-up duration was 9.7 years. Mortality rates in both groups were similar. Cumulative 5-month, 2-, and 10- year MACE-free survival rates of IRBT patients were 89%, 56% and 29%, respectively, while those of the control patients were 90%, 76% and 52%, respectively (p<0.001). The difference in the MACE rate was mainly driven by target vessel revascularisation (TVR) (p<0.001). Furthermore, two or more repeat TVRs were needed in 12% of IRBT patients and in only 6% of control patients (p<0.01). Adjusted hazard ratios for IRBT-associated all-cause mortality and MACE were 1.0 (95% CI 0.7-1.5) and 1.8 (95% CI 1.5-2.2), respectively. Conclusion: IRBT was associated with increased MACE between five months and two years of follow-up, mainly driven by repeat revascularisations. Similar event rate after two years indicate that there were no very late adverse effects related to IRBT.

Intracoronary optical coherence tomography and histology at 1 month and 2, 3, and 4 years after implantation of everolimus-eluting bioresorbable vascular scaffolds in a porcine coronary artery model: An attempt to decipher the human optical coherence tomography images in the ABSORB trial (Article)

2010-11-30T00:00:00Z

Background-: With the use of optical coherence tomography (OCT), alterations of the reflectance characteristics of everolimus-eluting bioresorbable vascular scaffold (BVS) struts have been reported in humans. In the absence of histology, the interpretation of the appearances of the struts by OCT remains speculative. We therefore report OCT findings with corresponding histology in the porcine coronary artery model immediately after and at 28 days and 2, 3, and 4 years after BVS implantation. Methods and results-: Thirty-five polymeric BVS (3.0×12.0 mm) were singly implanted in the main coronary arteries of 17 pigs that underwent OCT and were then euthanized immediately (n=2), at 28 days (n=2), at 2 years (n=3), at 3 years (n=5), or at 4 years (n=5) after implantation. All BVS-implanted arteries in these animals were evaluated by histology except for 5 arteries examined at 2 years with gel permeation chromatography to assess the biodegradation of the polymeric device. Fourteen arteries with BVS from an additional 6 pigs were examined by gel permeation chromatography at 1 (n=1), 1.5 (n=2), and 3 (n=2) years. Corresponding OCT and histology images were selected with the distal and proximal radiopaque markers used as landmarks. At 28 days, by OCT, 82% of struts showed sharply defined, bright reflection borders, best described as a box-shaped appearance. Histologically, all struts appeared intact with no evidence of resorption. At 2 years, by OCT, 60±20 struts were discernible per BVS with 80.4% of the strut sites as a box-shaped appearance. Despite their defined appearance by OCT, by histology, these structures appeared to be composed of proteoglycan, with polymeric material being at such low level as to be no longer quantifiable by chromatography. At 3 years, by OCT, recognizable struts decreased to 28±9 struts per BVS: 43.7% showed dissolved black box; 34.8%, dissolved bright box; 16.1%, open box; and 5.4%, preserved box appearance. Histology shows that connective tissue cells within a proteoglycan-rich matrix replaced the areas previously occupied by the polymeric struts and coalesced into the arterial wall. At 4 years, by OCT, 10±6 struts were recognizable as either dissolved black or dissolved bright box. In histology, these struts are minimally discernible as foci of low-cellular-density connective tissue. Relative to the prediction of histological type by OCT appearance, the preserved box appearance of OCT corresponds well with 2-year histology (86.4%), whereas the dissolved bright and black box appearances correspond to 3-year histology (88.0% and 90.7%, respectively). Struts indiscernible by OCT correspond to the integrated strut footprints seen at 4 years (100%). Conclusions-: Struts that are still discernible by OCT at 2 years are compatible with largely bioresorbed struts, as demonstrated by histological and gel permeation chromatography analysis. At 3 and 4 years, both OCT and histology confirm complete integration of the struts into the arterial wall.

The unrestricted use of sirolimus- and paclitaxel-eluting stents results in better clinical outcomes during 6-year follow-up than bare-metal stents: An analysis of the RESEARCH (Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital) and T-SEARCH (TaxusStent Evaluated at Rotterdam Cardiology Hospital) registries (Article)

2010-10-01T00:00:00Z

Objectives The aim of this study was to assess the 6-year clinical outcome after unrestricted use of sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) as compared with bare-metal stents (BMS) in consecutive de novo patients undergoing percutaneous coronary intervention (PCI). Background SES and PES have been shown to significantly decrease target vessel revascularization (TVR) rates compared with BMS in "real-world" registries. However, possible higher rates of very-late stent thrombosis and a restenosis "catch-up" trend might jeopardize the benefit. Methods Three PCI cohorts, each with exclusive use of 1 stent type (BMS = 450; SES = 508; PES = 576), were systematically followed for the occurrence of major adverse cardiac events (MACE). Results Very-late stent thrombosis was more common in SES and PES patients than BMS patients (2.4% vs. 0.9% vs. 0.4%, respectively; p = 0.02); however, there were no significant differences between the stent types for all-cause mortality and all-cause mortality/myocardial infarction at 6-year follow-up. Sixty-nine SES patients (Kaplan-Meier estimate 14%) and 72 PES patients (14%) had a TVR, as compared with 79 BMS patients (18%; log-rank p = 0.02), which maintained significance after adjustment for (potential) confounders. Multivariate analysis showed that DES implantation is associated with lower incidence of TVR and MACE than BMS implantation (hazard ratio: 0.65, 95% confidence interval: 0.49 to 0.86; p = 0.003; hazard ratio: 0.79, 95% confidence interval: 0.65 to 0.97; p = 0.02, respectively). Incidence of MACE was also lower in SES and PES patients (30% and 30%, respectively) than in BMS patients (34%); however, significance was borderline. Conclusions The unrestricted use of both DES resulted in a sustained advantage in decreasing TVR and, to a lesser extent, MACE compared with BMS at 6 years. The SES and PES are equally safe and effective in the treatment of coronary lesions.

Specific coronary drug-eluting stents interfere with distal microvascular function after single stent implantation in pigs (Article)

2010-07-01T00:00:00Z

Objectives The aim of this study was to compare the effects of single drug-eluting stents (DES) on porcine coronary function distal to the stent in vivo and in vitro. Background The mechanism of endothelial dysfunction occurring in human coronary conduit arteries up to 9 months after DES implantation is unknown. Methods A sirolimus-eluting stent (SES), paclitaxel-eluting stent (PES), and a bare-metal stent (BMS) were implanted in the 3 coronary arteries of 11 pigs. After 5 weeks, in vivo responses in distal coronary flow to different doses of bradykinin (BK) and nitrates were measured. In vitro, vasodilation to BK and nitrates, as well as vasoconstriction to endothelin (ET)-1 were assessed in both distal coronary conduit and small arteries. In addition, contributions of nitric oxide (NO) and endotheliumderived hyperpolarizing factors (EDHFs) and cyclic guanosine monophosphate (cGMP) responses to BK-stimulation were determined in vitro. Results Both DES did not alter in vivo distal vasomotion. In vitro distal conduit and small arterial responses to BK were also unaltered; DES did not alter the BK-induced increase in cGMP. However, after NO synthase blockade, PES showed a reduced BK-response in distal small arteries as compared with BMS and SES (p < 0.05). The ET-1-induced vasoconstriction and vascular smooth muscle cell function were unaltered. Conclusions In this study of single stenting in healthy porcine coronaries for 5 weeks, SES did not affect distal coronary vascular function, whereas PES altered distal endothelial function of small arteries under conditions of reduced NO bioavailability. Therefore, specifically the EDH-component of microvascular function seems affected by PES.

Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs (Article)

2010-03-01T00:00:00Z

Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18° C or 37° C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 ± 1% at baseline vs. -3 ± 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 ± 5%) and stroke volume (12 ± 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 ± 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 ± 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine ± inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37° C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis. Copyright

Complete percutaneous revascularization for multivessel disease in patients with impaired left ventricular function: Pre- and post-procedural evaluation by cardiac magnetic resonance imaging (Article)

2010-03-01T00:00:00Z

Objectives: The aim of this study was to investigate the effect of complete, incomplete, and unsuccessful revascularization by percutaneous coronary intervention (PCI) on left ventricular ejection fraction (EF) in patients with multivessel disease and impaired left ventricular function and assess the diagnostic accuracy of cardiac magnetic resonance imaging (MRI) for improvement in EF. Background: The effect of PCI for multivessel coronary artery disease on long-term myocardial function and the predictive value of cardiac MRI on global function are incompletely investigated. Methods: Cardiac MRI was performed in patients with multivessel disease before and 6 months after complete revascularization (n = 34) or incomplete revascularization (n = 22) or in patients without successful revascularization (n = 15). For the prediction of recovery of EF, wall thickening was quantified on cine images at rest and during 5- and 10-μg/kg/min dobutamine. The transmural extent of infarction was quantified on delayed enhancement cardiac MRI. Results: The EF improved significantly after complete revascularization (46 ± 12% to 51 ± 13%; p < 0.0001) but did not change after incomplete (49 ± 11% to 49 ± 10%; p = 0.88) or unsuccessful revascularization (49 ± 13% to 47 ± 13%; p = 0.11). Sensitivity, specificity, positive and negative predictive value for the prediction of improvement in EF of >4% after PCI were 100%, 75%, 74%, and 100%, respectively, for dobutamine-cardiac MRI and 70%, 77%, 70%, and 77%, respectively, for delayed enhancement-cardiac MRI. Conclusions: Complete revascularization for multivessel coronary artery disease improves EF, whereas EF did not change in patients after incomplete or unsuccessful revascularization. Improvement in EF can be predicted by performing cardiac MRI before PCI.

An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: A LEADERS trial sub-study (Article)

2010-01-01T00:00:00Z

AimsIncomplete endothelialization has been found to be associated with late stent thrombosis, a rare but devastating phenomenon, more frequent after drug-eluting stent implantation. Optical coherence tomography (OCT) has 10 times greater resolution than intravascular ultrasound and thus appears to be a valuable modality for the assessment of stent strut coverage. The LEADERS trial was a multi-centre, randomized comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer. This study sought to evaluate tissue coverage and apposition of stents using OCT in a group of patients from the randomized LEADERS trial.Methods and resultsFifty-six consecutive patients underwent OCT during angiographic follow-up at 9 months. OCT images were acquired using a non-occlusive technique at a pullback speed of 3 mm/s. Data were analysed using a Bayesian hierarchical random-effects model, which accounted for the correlation of lesion characteristics within patients and implicitly assigned analytical weights to each lesion depending on the number of struts observed per lesion. Primary outcome was the difference in percentage of uncovered struts between BESs and SESs. Twenty patients were included in the analysis in the BES group (29 lesions with 4592 struts) and 26 patients in the SES group (35 lesions with 6476 struts). A total of 83 struts were uncovered in the BES group and 407 out of 6476 struts were uncovered in the SES group [weighted difference-1.4, 95 confidence interval (CI)-3.7 to 0.0, P = 0.04]. Results were similar after adjustment for pre-procedure lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap. There were three lesions in the BES group and 15 lesions in the SES group that had ≥5 of all struts uncovered (difference-33.1, 95 CI-61.7 to-10.3, P < 0.01).ConclusionStrut coverage at an average follow-up of 9 months appears to be more complete in patients allocated to BESs when compared with SESs. The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determined. © Published on behalf of the European Society of Cardiology. All rights reserved.

Optical coherence tomography patterns of stent restenosis (Article)

2009-08-01T00:00:00Z

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.

Quinaprilat-eluting stents do not attenuate intimal thickening following stenting in porcine coronary arteries (Article)

2009-07-01T00:00:00Z

Objective: Vascular injury increases angiotensin-converting enzyme (ACE) activity in the vessel wall, and experimental evidence suggests that high-dose oral ACE inhibition reduces intimal hyperplasia following balloon angioplasty. Local drug delivery can achieve high local concentrations which may be especially efficacious in inhibiting tissue growth following stent implantation. The aim of this study was to evaluate the angiographic and histomorphologic effects of quinaprilat-eluting stents in normal porcine coronary arteries. Methods: Ten pigs received phosphorylcholine-coated stents in each of the three major coronary arteries: one loaded with 780 μg quinaprilat, one with the solvent and one non-loaded control. Quantitative angiography was performed before and after stenting and at 4 weeks follow-up. At this time point the stented arteries were also analyzed using histology and morphometry. Results: Repeated measures ANOVA yielded significantly smaller angiographic lumen in both quinaprilat and solvent groups: 2.62 ± 0.31 and 2.65 ± 0.31 mm, respectively versus control: 2.70 ± 0.32 mm at follow-up, p < 0.05. Histology confirmed this finding with an increment in intimal area (2.5 ± 0.86 mm2) and thickness (0.57 ± 0.29 mm) in the quinaprilat group; versus solvent (1.98 ± 0.57 mm20.4 ± 0.26 mm) and controls (1.92 ± 0.50 mm2and 0.41 ± 0.18 mm). Conclusion: Quinaprilat-eluting stents do not attenuate neointimal thickening following implantation in normal porcine coronary arteries, but rather show a tendency towards the opposite.

MAHOROBA, first-in-man study: 6-month results of a biodegradable polymer sustained release tacrolimus-eluting stent in de novo coronary stenoses (Article)

2009-06-01T00:00:00Z

AimsTo report the 4-month angiographic and 6-month clinical follow-up in first-in-man study using the tacrolimus-eluting bioabsorbable polymer-coated cobalt-chromium MAHOROBA™ stent.Methods and resultsA total of 47 patients with either stable angina or unstable angina, or silent myocardial ischaemia, based on a de novo coronary stenosis that could be covered by a single 18 mm stent in a native coronary artery with a diameter between 3.0 and 3.5 mm were enrolled at three sites. The primary endpoint was in-stent late loss at 4 months. The secondary endpoints include volume obstruction of the stents assessed by intravascular ultrasound (IVUS) at 4 months and major adverse cardiac events (MACE) at 6 months. Forty-seven patients were enrolled. Procedural success was achieved in 97.9. At 4-month follow-up, in-stent late loss was 0.99 ± 0.46 mm, whereas in-stent volume obstruction in IVUS was 34.8 ± 15.8. At 6 months, there were no deaths, but 2 patients suffered from a myocardial infarction and 11 patients required ischaemia-driven repeat revascularization. The composite MACE rate was 23.4.ConclusionThis tacrolimus-eluting stent failed to prevent neointimal hyperplasia, despite the theoretical advantages of the tacrolimus, which has less inhibitory effects on endothelial cells than smooth muscle cells.

Intravascular ultrasound and 3D angle measurements of coronary bifurcations (Article)

2009-06-01T00:00:00Z

Objective: To standardize the intravascular ultrasound (IVUS) analysis of coronary bifurcations. Background: Percutaneous treatment of bifurcation lesions is difficult particularly at the side branch ostium. Imaging techniques may improve our understanding of treatment options. There is no established IVUS methodology to assess the bifurcation. The present study aims to develop standards for bifurcation imaging. Methods: Quantitative IVUS analysis and 3D bifurcation angle measurements were performed in 34 patients who were selected from the Washington Hospital Center Database. Patients were included if both left anterior descending (LAD) and first diagonal (DX) pullbacks in the same procedure were done. Angiograms were available in 27 patients to measure the 3D bifurcation angle using specialized software. Pullbacks were analyzed proximal and distal to the bifurcation, and at the bifurcation. Results: ProxLADversus ProxLAD(DX)were similar for vessel area (15.5 ± 4.6 mm2vs. 15.9 ± 4.0 mm2, P 5 0.19), lumen area (8.3 ± 3.6 mm2vs. 8.6 ± 3.3 mm2, P = 0.25), and plaque area (7.2 ± 2.0 mm2vs. 7.3 ± 1.9 mm2, P = 0.55). However, BifurcationLADwas larger than BifurcationDXfor vessel area (17.3 ± 4.0 mm2vs. 16.6 ± 3.9 mm2, P = 0.0083). The 3D angiographic bifurcation angle was 50° ± 13° (range of 26°-84°), and did not affect the IVUS measurements. IVUS analysis showed that bifurcation lesions did obey Murray's Law, as ProxLADlumen area measured 36.7 ± 25.1 mm3versus DistLAD/DistDXmeasured 38.0 ± 29.1 mm3, P = 0.56. Conclusions: Two IVUS pullbacks should be performed for a complete assessment of the bifurcation and comparison with Murray's Law. The proposed IVUS analysis was not influenced by the bifurcation angle.

Lowering the Dose of Sirolimus, Released From a Nonpolymeric Hydroxyapatite Coated Coronary Stent, Reduces Signs of Delayed Healing (Article)

2009-04-01T00:00:00Z

Objectives: The aim of this study was to compare efficacy of low- and high-dose sirolimus release (25, 40, or 100 μg) from hydroxyapatite (HAp) with Cypher (Cordis, Johnson & Johnson, Warren, New Jersey) (111 μg sirolimus) in porcine coronary arteries. Background: Polymer-based sirolimus-eluting stents such as Cypher interfere with vascular healing, probably due to the permanent presence of the polymer coating and the high sirolimus dose. The use of low-dose sirolimus and inert nonpolymeric but biodegradable coatings such as HAp might be more appropriate. Methods: Stents (n = 68) were implanted, guided by quantitative coronary angiography. All swine received clopidogrel and acetylsalicylic acid during 28 days follow-up. Safety of the coating in absence of drugs was studied by comparing HAp with and without a lipid-based release regulating layer (HApR) with bare-metal stents. Efficacy was studied by comparing the release of 25, 40, and 100 μg sirolimus with Cypher. Results: The safety study (without drug) revealed no differences in neointimal thickening in response to HAp and HApR with complete healing in all groups. Dose response analysis showed that neointimal thickening was similar in all groups regardless of sirolimus dose, with a normal appearance of the endothelium. There was, however, a dose-dependent increase in fibrinoid (p = 0.028), considered to be a marker of delayed healing. The Cypher stent induced the highest amount of fibrinoid. Conclusions: Reducing the dose of sirolimus eluting from a biocompatible HAp coated stent reduces signs of delayed vascular healing, without affecting neointimal hyperplasia.

Late stent thrombosis, endothelialisation and drug-eluting stents (Article)

2009-04-01T00:00:00Z

Drug-eluting stents (DES) significantly reduce the risk of restenosis after percutaneous coronary revascularisation, but an increased risk of late stent thrombosis (LST) has been put forward as a major safety concern. Meta-analysis of clinical trials, however, does not support this caveat. Even so, many interventional cardiologists think that LST is associated with DES and related to delayed endothelialisation. This hypothesis is based on autopsy studies and clinical intracoronary angioscopy. In autopsy studies, differences between endothelialisation of DES and baremetal stents (BMS) have been reported. Most preclinical studies, however, have failed to show any significant differences in endothelialisation between DES and BMS. Our own studies, using the porcine coronary artery model, also suggest that DES show no differences in re-endothelialisation. However, DES do delay vascular healing and induce endothelial dysfunction. This paper will review clinical and animal studies which consider re-endothelialisation and LST.

Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: The problem of treatment selection bias (Article)

2009-03-01T00:00:00Z

AimsIn several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial.Methods and resultsThe study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95 confidence interval (CI) 0.37-0.96] and 0.46 (95 CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95 CI 0.70-1.74) for death and 1.27 (95 CI 0.88-1.85) for death or spontaneous MI.ConclusionThe ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies.

Stem cell therapy for chronic heart failure (Article)

2009-01-01T00:00:00Z

Endothelial dysfunction after drug eluting stent implantation. (Article)

2009-01-01T00:00:00Z

Endothelial dysfunction has been implicated in the pathological process of coronary artery disease as well as an adverse event after coronary drug eluting stent (DES) implantation. In this review, an overview will be given of the evidence to date regarding the effects of coronary DES on endothelial function obtained from both clinical and experimental studies. Stenting in general and DES seem to impair several aspects of endothelial function: provision of a permeable barrier function; modulation of adhesion, thrombosis and inflammation; and regulation of vascular tone. However, new insights show that the effects of DES can extend beyond the stent and peri-stent area: the vascular bed distal to the stent, starting with the distal conduit vessels up to the distal microvasculature, might be at risk. In addition, insight into the mechanism of DES induced endothelial dysfunction has been gained. To finalize this review, clinical complications and solutions of DES associated endothelial dysfunction will be discussed.

A randomized comparison of the magnetic navigation system versus conventional percutaneous coronary intervention (Article)

2008-11-15T00:00:00Z

Objective: A randomized comparison of the magnetic navigation system (MNS) to conventional guidewire techniques in percutaneous coronary interventions. Background: The MNS precisely directs a magnetized guidewire in vivo through two permanent external magnets. Methods: A total of 111 consecutive patients were enrolled. Crossing success, crossing-/fluoroscopy times, and contrast usage were directly compared. Lesions were classified according to the AHA/ACC criteria. Three tertiles of vessel/lesion complexity [low (<5), medium (6-10) and high (>10)] were defined using 3D reconstructions and angiographic information. Results: The crossing success for magnetic and the conventional wires were 93.3and 95.6%, respectively. Crossing and fluoroscopy times were longer with the magnetic wires (72.9 ± 50.3 sec vs. 58.1 ± 47.2 sec, P < 0.001 and 66.2 ± 44.1 sec vs. 55.2 ± 44.4 sec, P 5 0.03, respectively). In vessels with low and medium complexity the magnetic wires had significantly longer times (P < 0.001) but for those with high scores (>10) a trend towards shorter times was observed. The MNS resulted in a small but significant reduction in contrast usage (2.3 ± 3.5 ml vs. 4.5 ± 4.4 ml, P < 0.001). Moreover by superimposing a virtual roadmap of the vessel on the live fluoroscopy image 48% of the lesions were crossed without requiring contrast agents with the MNS. Conclusion: The MNS has comparable crossing success to conventional PCI. It is relatively slower but there is a trend to support a potential advantage in more complex vessels. By simultaneously employing a virtual roadmap there is a small but significant reduction in contrast usage.

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

2008-10-01T00:00:00Z

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. Copyright

Accurate Automatic Papillary Muscle Identification for Quantitative Left Ventricle Mass Measurements in Cardiac Magnetic Resonance Imaging (Article)

2008-10-01T00:00:00Z

Rationale and Objectives: We sought to evaluate the automatic detection of the papillary muscle and to determine its influence on quantitative left ventricular (LV) mass assessment. Materials and Methods: Twenty-eight Yorkshire-Landrace swine and 10 volunteers underwent cardiac magnetic resonance imaging (CMR) of the left ventricle. The variability in measurements of LV papillary muscles traced automatically and manually were compared to intra- and interobserver variabilities. CMR-derived LV mass with the papillary muscle included or excluded from LV mass measurements was compared to true mass at autopsy of the Yorkshire-Landrace swine. Results: Automatic LV papillary muscle mass from all subjects correlated well with manually derived LV papillary muscle mass measurements (r = 0.84) with no significant bias between both measurements (mean difference ± SD, 0.0 ± 1.5 g; P = .98). The variability in results related to the contour detection method used was not statistically significant different compared to intra- and interobserver variabilities (P = .08 and P = .97, respectively). LV mass measurements including the papillary muscle showed significantly less underestimation (-10.6 ± 7.1 g) with the lowest percentage variability (6%) compared to measurements excluding the papillary muscles (mean underestimation, -15.1 ± 7.4 g percentage variability, 7%). Conclusion: The automatic algorithm for detecting the papillary muscle was accurate with variabilities comparable to intra- and interobserver variabilities. LV mass is determined most accurately when the papillary muscles are included in the LV mass measurements. Taken together, these observations warrant the inclusion of automatic contour detection of papillary muscle mass in studies that involve the determination of LV mass.

Assessment of Culprit and Remote Coronary Narrowings Using Optical Coherence Tomography With Long-Term Outcomes (Article)

2008-08-15T00:00:00Z

Much currently known information about vulnerable plaque stems from postmortem studies that identified several characteristics making them prone to rupture, including the presence of a thin fibrous cap and a large lipid core. This study used optical coherence tomography (OCT) to assess culprit and remote coronary narrowings and investigate whether intracoronary OCT in living patients was able to visualize morphologic features associated with vulnerable plaque in postmortem studies. Twenty-three patients successfully underwent OCT before percutaneous coronary intervention. The culprit lesion and mild to moderate coronary narrowings remote from the target stenosis were investigated. Using OCT, the culprit lesion was found to be fibrous in 39.1%, fibrocalcific in 34.4%, and lipid rich in 26.1% of cases. Two patients met criteria for thin-cap fibroatheroma (TCFA; defined as the presence of a signal-rich fibrous cap covering a signal-poor lipid/necrotic core with cap thickness <0.2 mm). Most plaques at remote segments were proximal to the culprit lesion (73.9%) and predominantly fibrous and lipid rich. OCT identified 7 TCFA lesions in 6 patients with a mean cap thickness of 0.19 ± 0.05 mm, extending for 103° ± 49° of the total vessel circumference. At 24 months of clinical follow-up, the only event occurred in a patient with in-stent restenosis who underwent repeated percutaneous revascularization. There were no clinically apparent plaque rupture-related events in the 6 patients found to have remote TCFA. This study showed that OCT can be safely applied to image beyond the culprit lesion and can detect in vivo morphologic features associated with plaque vulnerability using retrospective pathologic examination. In conclusion, detection of TCFA, particularly in stable patients, is desirable and may principally allow for early intervention and prevention of adverse events.

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

2008-06-01T00:00:00Z

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.

Functional and structural adaptations of coronary microvessels distal to a chronic coronary artery stenosis (Article)

2008-04-01T00:00:00Z

Distal to a chronic coronary artery stenosis, structural remodeling of the microvasculature occurs. The microvascular functional changes distal to the stenosis have not been studied in detail. We tested the hypothesis that microvascular structural remodeling is accompanied by altered regulation of coronary vasomotor tone with increased responsiveness to endothelin-1. Vasomotor tone was studied in coronary microvessels from healthy control swine and from swine 3 to 4 months after implantation of an occluder that causes a progressive coronary narrowing, resulting in regional left ventricular dysfunction and blunted myocardial vasodilator reserve. Arterioles (≈200-μm passive inner diameter at 60 mm Hg) were isolated from regions perfused by the stenotic left anterior descending and normal left circumflex coronary arteries and studied in vitro. Passive pressure-diameter curves demonstrated reduced distensibility of subendocardial left anterior descending compared with subendocardial left circumflex or control arterioles, suggestive of structural remodeling. Myogenic responses were blunted in subendocardial left anterior descending compared with left circumflex arterioles, reflecting altered smooth muscle function. However, vasodilator responses to nitroprusside and bradykinin were not different in the endocardium, suggesting preserved endothelium and smooth muscle responsiveness. Finally, vasoconstrictor responses to endothelin-1 were enhanced in left anterior descending arterioles compared with left circumflex or control arterioles. Regional myocardial vascular conductance responses to bradykinin and endothelin in vivo confirmed the in vitro observations. In conclusion, inward remodeling of coronary microvessels distal to a stenosis is accompanied by exaggerated vasoconstrictor responses to endothelin-1. These structural and functional alterations may aggravate flow abnormalities distal to a chronic coronary artery stenosis.

Intracoronary infusion of autologous mononuclear bone marrow cells in patients with acute myocardial infarction treated with primary PCI: Pilot study of the multicenter HEBE trial (Article)

2008-02-05T00:00:00Z

Objective: This study was a pilot trial to determine safety and feasibility of intracoronary infusion of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction (MI). Background: Studies reporting the effect of MBMC therapy on improvement of left ventricular (LV) function have shown variable results. The HEBE trial is a large multicenter, randomized trial that currently enrolls patients. Prior to this trial we performed a pilot study. Methods: Twenty-six patients with a first acute MI were prospectively enrolled in eight centers. Bone marrow aspiration was performed at a median of 6 days after primary PCI (interquartile range, 5-7 days). MBMC were isolated by gradient centrifugation and were infused intracoronary the same day. All patients underwent magnetic resonance imaging before cell infusion and after 4 months. Clinical events were assessed up to 12 months. Results: Within 10 hr after bone marrow aspiration, 246 ± 133 × 106MBMC were infused, of which 3.9 ± 2.3 × 106cells were CD34+. In one patient, this procedure was complicated by local dissection. LV ejection fraction significantly increased from 45.0 ± 6.3% to 47.2 ± 6.5% (P = 0.03). Systolic wall thickening in dysfunctional segments at baseline improved with 0.9 ± 0.7 mm (P < 0.001). Infarct size decreased 37% from 17.8 ± 8.2 to 11.2 ± 4.2 gram (P < 0.001). During 12-month follow-up, 3 additional revascularizations were performed and an ICD was implanted in one patient, 3 weeks after PCI. Conclusion: In patients with acute MI, intracoronary infusion of MBMC is safe in a multicenter setting. At 4-month follow-up, a modest increase in global and regional LV function was observed, with a concomitant decrease in infarct size.

First direct in vivo comparison of two commercially available three-dimensional quantitative coronary angiography systems (Article)

2008-01-01T00:00:00Z

Aim: The in vivo comparison of the accuracy of two 3-dimensional quantitative coronary angiography (QCA) systems. Methods: Precision-drilled plexiglass phantoms with five different luminal diameters (0.5-1.9 mm) were percutaneously inserted into the coronary arteries of four Yorkshire pigs. Twenty-one angiographic images of these stenotic phantoms were acquired for in vivo validation testing. Quantitative assessments of the minimum, maximum, and mean luminal diameters together with the minimum luminal area were determined using two 3D QCA systems, the CardiOp-B® and CAAS 5. Results: The CardiOp-B system significantly underestimated the minimum luminal diameter MLD whilst both systems significantly overestimated the maximum luminal diameter at the minimal luminal area (MLA) over the phantom's true value. The CAAS 5 system had a greater degree of accuracy/mm (mean difference = 0.01 vs. 0.03) and precision/mm (SD = 0.09 vs. 0.23) than the CardiOp-B in assessing the minimal LD. An increased precision/mm (SD = 0.01 vs. 0.29) and accuracy/mm (mean difference = 0.03 vs. 0.11) in the mean LD was observed with the CAAS 5. In comparing the MLA/mm2the CAAS 5 was more precise/mm2(SD = 0.14 vs. 0.55) and accurate/mm2(mean difference = 0.12 vs. 0.02) to the true phantom MLA compared to the CardiOp-B system. Conclusions: In a 21 phantom study, the CAAS 5 3D QCA system had a greater degree of accuracy and precision in both the luminal and area measurements than the CardiOp-B 3D QCA system.

Fat is not all bad: How to make good use of adipose tissue (Article)

2007-11-01T00:00:00Z

Chronic total occlusion treatment in post-CABG patients: Saphenous vein graft versus native vessel recanalization - Long-term follow-up in the drug-eluting stent era (Article)

2007-07-01T00:00:00Z

Objective: To compare the postprocedural and long-term clinical outcomes of two groups of patients, all presenting with chronic saphenous vein graft (SVG) occlusion, who underwent either SVG or native vessel reopening. Background: Chronic total occlusions (CTO) treatment in patients who underwent previous surgical revascularization is a dilemma and the choice of performing native vessel or SVG recanalization is not always easy. Methods: Between July 2002 and October 2004, a total of 260 patients were successfully treated for a CTO. Of them, we selected all patients (n = 24) who had previous bypass surgery with graft occlusion. Of this final group, 13 patients underwent a percutaneous graft recanalization while 11 underwent native vessel reopening. Results: Primary end points were in-hospital and 3-year rates of death, myocardial infarction, target lesion revascularization, and target vessel revascularization. No events occurred in either group during the in-hospital period. Cumulative 3-year event-free survival in the native vessel and SVG group was 81.8% and 83.9% respectively (P = NS). One death and one TVR occurred in each group. Conclusion: In selected cases, SVG reopening instead of the native vessel is feasible. In such a high-risk population, drug-eluting stent implantation in both SVG and native CTO lesions is associated with good long-term outcomes.

Intracoronary delivery of umbilical cord blood derived unrestricted somatic stem cells is not suitable to improve LV function after myocardial infarction in swine (Article)

2007-04-01T00:00:00Z

Regeneration of infarcted myocardium by injecting stem cells has been proposed to prevent heart failure. We studied the i.c. administration of human umbilical cord blood stem cells (USSC) in a porcine model of myocardial infarction (MI) and reperfusion. In 15 swine, MI was induced by balloon-occlusion of the left circumflex coronary artery (LCX) for 2 h followed by reperfusion. Five swine served as healthy controls. One week later, magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function and infarct size. Then, under immune suppression, 6 of the 12 surviving MI swine received intracoronary injection of ∼ 108human USSC in the LCX while the other MI-swine received medium. Four weeks later all swine underwent follow-up MRI, and were sacrificed for histology. One week after MI, end-diastolic volume (92 ± 3 mL) and LV mass (75 ± 2 g) were larger, while ejection fraction (42 ± 2%) was smaller than in healthy control (68 ± 3 mL, 66 ± 3 g and 55 ± 3%, all P < 0.05). Regional wall thickening (- 7 ± 2%) in the LCX area became akinetic. No difference in global and regional LV function at 5 weeks was observed between MI animals receiving USSC or medium. Infarct size after USSC treatment was significantly larger (20 ± 3 g vs. 8 ± 2 g, P < 0.05). USSC survived only in the infarct border zone at 5 weeks and did not express cardiomyocyte or endothelial markers. Histology showed that intracoronary injection of USSC caused micro infarctions by obstructing blood vessels. In swine with a 1 week old MI, injection of USSC via the intracoronary route does not improve LV function 4 weeks later.

Drug-eluting stents show delayed healing: Paclitaxel more pronounced than sirolimus (Article)

2007-04-01T00:00:00Z

Aims: To understand wound healing after drug-eluting stents (DES) placement in humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by atherectomy from bare metal stents (BMS) and DES in comparison with de novo atherosclerosis. Methods and results: The tissue was retrieved from ISR in ten sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS, and nine stenotic de novo atherosclerotic lesions and processed for histology and immunocytochemistry. Patients with ISR in PES showed a significantly higher incidence of unstable angina upon presentation for re-intervention (P = 0.046). De novo tissue tended to be more collagen rich, whereas ISR tissue tended to be more proteoglycan rich. In all groups, cell content consisted almost exclusively of smooth muscle cells. Histology showed that fibrinoid in ISR tissue was present only in DES (P = 0.004), as late as 2 years following DES placement, indicating a persistent incomplete healing response. The amount of fibrinoid, given as a percentage of total tissue in each atherectomy specimen, was greater in PES than in SES (17 vs. 5%, P = 0.026). Conclusion: ISR in DES shows incomplete neointimal healing as late as 2 years after implantation. Patients with ISR in PES presented with more unstable angina and showed more pronounced signs of delayed healing than SES.

Assessment of acute reperfused myocardial infarction with delayed enhancement 64-MDCT. (Article)

2007-02-01T00:00:00Z

OBJECTIVE: The purpose of this study was to evaluate the utility of delayed enhancement 64-MDCT in the assessment of myocardial infarct size in a porcine model of acute reperfused myocardial infarction. CT can be used for noninvasive assessment of coronary artery stenosis, but to our knowledge, evaluation of myocardial viability in the subacute phase of acute myocardial infarction has not been validated. We performed delayed enhancement imaging on six domestic swine 5 days after reperfused acute myocardial infarction and assessed the relation between delayed enhancement patterns in vivo and the extent of viable and nonviable myocardium at postmortem histochemical analysis. CONCLUSION: Delayed enhancement imaging with 64-MDCT can be used for accurate assessment of the size of reperfused acute myocardial infarcts.

Recovery of left ventricular function after primary angioplasty for acute myocardial infarction. (Article)

2005-06-01T00:00:00Z

AIMS: To study recovery of segmental wall thickening (SWT), ejection fraction (EF), and end-systolic volume (ESV) after acute myocardial infarction (AMI) in patients who underwent primary stenting with drug-eluting stents. Additionally, to evaluate the predictive value of magnetic resonance imaging (MRI)-based myocardial perfusion and delayed enhancement (DE) imaging. METHODS AND RESULTS: Twenty-two patients underwent cine-MRI, first-pass perfusion, and DE imaging 5 days after successful placement of a drug-eluting stent in the infarct-related coronary artery. Regional myocardial perfusion and the transmural extent of DE were evaluated. A per patient perfusion score was calculated and consisted of a summation of all segmental scores. Myocardial infarct size was quantified by measuring the volume of DE. At 5 months after AMI, cine-MRI was performed and SWT, EF, and ESV were quantified. EF increased from 48+/-11 to 55+/-9% (P<0.01). SWT at 5 months was inversely related to baseline segmental DE scores (P<0.001) and segmental perfusion scores (P<0.001). EF and ESV at 5 months were related to acute infarct size (R(2)=0.65; P<0.001 and R(2)=0.78; P<0.001, respectively) and the calculated perfusion score (R(2)=0.23; P=0.02 and R(2)=0.14; P=0.09, respectively) at baseline. CONCLUSION: Marked recovery of left ventricular function was observed in patients receiving a drug-eluting stent for AMI. DE imaging appears to be a better prognosticator than perfusion imaging.

Short- and long-term clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: insights from the Rapamycin-Eluting and Taxus Stent Evaluated At Rotterdam Cardiology Hospital registries (RESEARCH and T-SEARCH). (Article)

2005-03-22T00:00:00Z

BACKGROUND: The impact of drug-eluting stent (DES) implantation on the incidence of major adverse cardiovascular events in patients undergoing percutaneous intervention for left main (LM) coronary disease is largely unknown. METHODS AND RESULTS: From April 2001 to December 2003, 181 patients underwent percutaneous coronary intervention for LM stenosis at our institution. The first cohort consisted of 86 patients (19 protected LM) treated with bare metal stents (pre-DES group); the second cohort comprised 95 patients (15 protected LM) treated exclusively with DES. The 2 cohorts were well balanced for all baseline characteristics. At a median follow-up of 503 days (range, 331 to 873 days), the cumulative incidence of major adverse cardiovascular events was lower in the DES cohort than in patients in the pre-DES group (24% versus 45%, respectively; hazard ratio [HR], 0.52 [95% CI, 0.31 to 0.88]; P=0.01). Total mortality did not differ between cohorts; however, there were significantly lower rates of both myocardial infarction (4% versus 12%, respectively; HR, 0.22 [95% CI, 0.07 to 0.65]; P=0.006) and target vessel revascularization (6% versus 23%, respectively; HR, 0.26 [95% CI, 0.10 to 0.65]; P=0.004) in the DES group. On multivariate analysis, use of DES, Parsonnet classification, troponin elevation at entry, distal LM location, and reference vessel diameter were independent predictors of major adverse cardiovascular events. CONCLUSIONS: When percutaneous coronary intervention is undertaken at LM lesions, routine DES implantation, which reduces the cumulative incidence of myocardial infarction and the need for target vessel revascularization compared with bare metal stents, should currently be the preferred strategy.

One year clinical follow up of paclitaxel eluting stents for acute myocardial infarction compared with sirolimus eluting stents (Article)

2005-01-01T00:00:00Z

OBJECTIVE: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. DESIGN AND PATIENTS: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period. SETTING: Academic tertiary referral centre. RESULTS: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p = 1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p = 0.04). This was driven by stent thrombosis (n = 4), especially in the bifurcation stenting (n = 2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p = 0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p = 0.16). CONCLUSIONS: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.

Long term outcome after intracoronary beta radiation therapy (Article)

2005-01-01T00:00:00Z

OBJECTIVES: To determine the long term outcome after intracoronary beta radiation therapy (IRT). SETTING: Tertiary referral centre. METHODS: The rate of major adverse cardiac events (MACE) was retrospectively determined in 301 consecutive patients who were treated with IRT. MACE was defined as death, myocardial infarction, or any reintervention. Long term clinical outcome was obtained from an electronic database of hospital records and from questionnaires to the patients and referring physicians. Long term survival status was assessed by written inquiries to the municipal civil registries. RESULTS: The mean (SD) follow up was 3.6 (1.2) years. The cumulative incidence of MACE at six months was 19.1%, at one year 36.4%, and at four years 58.3%. The target lesion revascularisation (TLR) rate at six months was 12.9%, at one year 28.3%, and at four years 50.4%. From multivariate analysis, dose < 18 Gy was the most significant predictor of TLR. At four years the cumulative incidence of death was 3.8%, of myocardial infarction 13.4%, and of coronary artery bypass surgery 11.3%. Total vessel occlusion was documented in 12.3% of the patients. CONCLUSIONS: In the long term follow up of patients after IRT, there are increased adverse cardiac events beyond the first six months.

Direct stenting versus direct stenting followed by centered beta-radiation with intravascular ultrasound-guided dosimetry and long-term anti-platelet treatment: results of a randomized trial: Beta-Radiation Investigation with Direct Stenting and Galileo in Europe (BRIDGE). (Article)

2004-08-04T00:00:00Z

Abstract OBJECTIVES: We sought to assess the efficacy of vascular brachytherapy (VBT) combined with stenting for the primary prevention of restenosis. BACKGROUND: Intravascular brachytherapy after stent implantation for de novo lesions has been abandoned for the present. We revisited this procedure by optimizing all procedural steps-the use of glycoprotein IIb/IIa blockers, direct stenting, adequate radiation coverage, avoidance of edge damage, source centering, intravascular ultrasound-guided dosimetry, and continuation of a dual anti-platelet regimen for one year. METHODS: The Beta-Radiation Investigation with Direct stenting and Galileo in Europe (BRIDGE) study is a multicenter, randomized controlled trial evaluating the long-term efficacy of VBT with P-32 (20 Gy at 1 mm in the coronary wall) after direct stenting. The primary end point was angiographic intra-stent late loss; secondary end points were six months binary restenosis and neo-intimal hyperplasia. Patients (n = 112) with de novo lesions (2.5 to 4.0 mm in diameter up to 15 mm long) were randomized to either VBT or no-VBT. RESULTS: At six months, intra-stent loss was 0.43 and 0.84 mm (p < 0.001) in the irradiated and control groups, respectively. Intra-stent neo-intimal volume was reduced from 36 mm3 to 10 mm3. However, in the irradiated group there were six late occlusions as well as eight restenoses outside the stented and peri-stented area at the fall-off dose edges of the irradiated area. Accordingly, the target vessel revascularization and major adverse cardiac and cerebrovascular events rates at one year in the VBT group (20.4% and 25.9%, respectively) were higher than in the control group (12.1% and 17.2%, respectively). CONCLUSIONS: Despite the optimization of pre-, peri-, and post-procedural factors and despite the relative efficacy of the brachytherapy for the prevention of the intra-stent neo-intimal hyperplasia, the clinical outcome of the irradiated group was less favorable than that of the control group.

Clinical outcomes for sirolimus-eluting stent implantation and vascular brachytherapy for the treatment of in-stent restenosis. (Article)

2004-07-01T00:00:00Z

Abstract The purpose of this study was to compare the mid-term clinical outcome of sirolimus-eluting stent (SES) implantation and vascular brachytherapy (VBT) for in-stent restenosis (ISR). We assessed the 9-month occurrence of major adverse cardiac events (MACE) in 44 consecutive patients with ISR treated with SES implantation and 43 consecutive patients treated with VBT in the period immediately prior. Baseline clinical and angiographic characteristics of the two groups were similar. During follow-up, three patients (7%) died in the VBT group and none in the SES group. The incidence of myocardial infarction was 2.3% in both groups. Target lesion revascularization was performed in 11.6% of the VBT patients and 16.3% of the SES patients (P = NS). The 9-month MACE-free survival was similar in both groups (79.1% VBT vs. 81.5% SES; P = 0.8 by log rank). The result of this nonrandomized study suggests that sirolimus-eluting stent implantation is at least as effective as vascular brachytherapy in the treatment of in-stent restenosis.

Post-sirolimus-eluting stent restenosis treated with repeat percutaneous intervention: late angiographic and clinical outcomes. (Article)

2004-06-01T00:00:00Z

BACKGROUND: We evaluated the clinical and angiographic outcomes of patients presenting with restenosis after sirolimus-eluting stent (SES) implantation treated with repeated percutaneous intervention. METHODS AND RESULTS: A total of 24 consecutive patients have undergone repeated percutaneous intervention to treat post-SES restenosis (27 lesions). The restenosis was located within the stent in 93% of lesions. From the 27 lesions, 1 (4%) was re-treated with a bare stent, 3 (11%) were treated with balloon dilatation, and the remaining 23 lesions (85%) were treated with repeated drug-eluting stent implantation (SES in 12 lesions [44%], paclitaxel-eluting stents in 11 lesions [41%]). The event-free survival rate was 70.8% after a median follow-up of 279 days from the post-SES treatment. The overall recurrent restenosis rate was 42.9%. The risk of recurrent restenosis was increased for patients with hypercholesterolemia, previous angioplasty, failed brachytherapy, post-SES restenosis needing early (<6 months) treatment, and post-SES restenosis treated with balloon dilatation. The recurrent restenosis rate of originally de novo lesions re-treated with drug-eluting stents was 18.2%. CONCLUSIONS: Even though de novo lesions treated with SES at baseline and re-treated with drug-eluting stents had reasonably better outcomes than other lesion types and strategies, our study shows that the treatment of post-SES restenosis is currently suboptimal and warrants further investigation.

Very long sirolimus-eluting stent implantation for de novo coronary lesions. (Article)

2004-04-01T00:00:00Z

Long-length stenting has a poor outcome when bare metal stents are used. The safety and efficacy of the sirolimus-eluting stent (SES) in long lesions has not been evaluated. Therefore, the aim of the present study was to evaluate the clinical and angiographic outcomes of SES implantation over a very long coronary artery segment. Since April 2002, all patients treated percutaneously at our institution received a SES as the device of choice as part of the Rapamycin Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. During the RESEARCH registry, stents were available in lengths of 8, 18, and 33 mm. The present report includes a predefined study population consisting of patients treated with >36-mm-long stented segments. Patients had a combination of >or=2 overlapping stents at a minimum length of 41 mm (i.e., one 33-mm SES overlapping an 8-mm SES) to treat native de novo coronary lesions. The incidence of major cardiac adverse events (death, nonfatal myocardial infarction, and target lesion revascularization) was evaluated. The study group comprised 96 consecutive patients (102 lesions). Clinical follow-up was available for all patients at a mean of 320 days (range 265 to 442). In all, 20% of long-stented lesions were chronic total occlusions, and mean stented length per lesion was 61.2 +/- 21.4 mm (range 41 to 134). Angiographic follow-up at 6 months was obtained in 67 patients (71%). Binary restenosis rate was 11.9% and in-stent late loss was 0.13 +/- 0.47 mm. At long-term follow-up (mean 320 days), there were 2 deaths (2.1%), and the overall incidence of major cardiac events was 8.3%. Thus, SES implantation appears safe and effective for de novo coronary lesions requiring multiple stent placement over a very long vessel segment.

Clinical and angiographic outcomes after overdilatation of undersized sirolimus-eluting stents with largely oversized balloons: an observational study. (Article)

2004-04-01T00:00:00Z

The purpose of this study was to assess the safety and effectiveness of sirolimus-eluting stent (SES) postdilatation with largely oversized balloons. We evaluated the clinical outcome of 68 consecutive patients enrolled in the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry who underwent percutaneous coronary intervention with SES implantation and further postdilatation with balloons > 1 mm larger than the stent nominal size. Angiographic follow-up was either scheduled for selected subgroups or clinically driven. Overall, 75 lesions were treated. The procedure was successful in 98.5% of the cases. One patient (1.5%) underwent emergency coronary bypass surgery for acute vessel occlusion. During 10.1 +/- 1.7 months of follow-up, three patients (4.5%) died, one (1.5%) had acute myocardial infarction, and four (6%) had target vessel revascularization. At angiographic follow-up, loss index was 0.13 +/- 0.34 and restenosis rate was 7.7%. Although not routinely recommended in every patient, SES postdilatation with largely oversized balloons appears a safe and effective strategy for selected patients.

Clinical, angiographic, and procedural predictors of angiographic restenosis after sirolimus-eluting stent implantation in complex patients (Article)

2004-03-23T00:00:00Z

BACKGROUND: The factors associated with the occurrence of restenosis after sirolimus-eluting stent (SES) implantation in complex cases are currently unknown. METHODS AND RESULTS: A cohort of consecutive complex patients treated with SES implantation was selected according to the following criteria: (1) treatment of acute myocardial infarction, (2) treatment of in-stent restenosis, (3) 2.25-mm diameter SES, (4) left main coronary stenting, (5) chronic total occlusion, (6) stented segment >36 mm, and (7) bifurcation stenting. The present study population was composed of 238 patients (441 lesions) for whom 6-month angiographic follow-up data were obtained (70% of eligible patients). Significant clinical, angiographic, and procedural predictors of post-SES restenosis were evaluated. Binary in-segment restenosis was diagnosed in 7.9% of lesions (6.3% in-stent, 0.9% at the proximal edge, 0.7% at the distal edge). The following characteristics were identified as independent multivariate predictors: treatment of in-stent restenosis (OR 4.16, 95% CI 1.63 to 11.01; P<0.01), ostial location (OR 4.84, 95% CI 1.81 to 12.07; P<0.01), diabetes (OR 2.63, 95% CI 1.14 to 6.31; P=0.02), total stented length (per 10-mm increase; OR 1.42, 95% CI 1.21 to 1.68; P<0.01), reference diameter (per 1.0-mm increase; OR 0.46, 95% CI 0.24 to 0.87; P=0.03), and left anterior descending artery (OR 0.30, 95% CI 0.10 to 0.69; P<0.01). CONCLUSIONS: Angiographic restenosis after SES implantation in complex patients is an infrequent event, occurring mainly in association with lesion-based characteristics and diabetes mellitus.

Treatment of very small vessels with 2.25-mm diameter sirolimus-eluting stents (from the RESEARCH registry). (Article)

2004-03-01T00:00:00Z

A total of 91 patients with 112 lesions received 2.25-mm sirolimus-eluting stents (SESs), and these lesions were compared with those treated with SESs of ≥2.5-mm diameter in the same procedure (n = 109). The reference diameters were 1.88 ± 0.34 and 2.52 ± 0.57 mm, respectively (p <0.01). At follow-up, the late lumen loss was 0.07 ± 0.48 mm for the 2.25-mm SES versus 0.03 ± 0.38 mm for the larger SES (p = 0.5), and the binary restenosis rate was 10.7% versus 3.9%, respectively (p = 0.1). The 12-month target lesion revascularization rate was 5.5%. In conclusion, 2.25-mm SESs were associated with low rates of clinical and angiographic late complications.

Unrestricted utilization of sirolimus-eluting stents compared with conventional bare stent implantation in the "real world": the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. (Article)

2004-01-20T00:00:00Z

BACKGROUND: The effectiveness of sirolimus-eluting stents in unselected patients treated in the daily practice is currently unknown. METHODS AND RESULTS: Sirolimus-eluting stent implantation has been used as the default strategy for all percutaneous procedures in our hospital as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. Consecutive patients with de novo lesions (n=508) treated exclusively with sirolimus-eluting stents (SES group) were compared with 450 patients who received bare stents in the period just before (pre-SES group). Patients in the SES group more frequently had multivessel disease, more type C lesions, received more stents, and had more bifurcation stenting. At 1 year, the cumulative rate of major adverse cardiac events (death, myocardial infarction, or target vessel revascularization) was 9.7% in the SES group and 14.8% in the pre-SES group (hazard ratio [HR], 0.62 [95% CI, 0.44 to 0.89]; P=0.008). The 1-year risk of clinically driven target vessel revascularization in the SES group and in the pre-SES group was 3.7% versus 10.9%, respectively (HR, 0.35 [95% CI, 0.21 to 0.57]; P<0.001). CONCLUSIONS: Unrestricted utilization of sirolimus-eluting stents in the "real world" is safe and effective in reducing both repeat revascularization and major adverse cardiac events at 1 year compared with bare stent implantation.

Intravascular ultrasound evaluation after sirolimus eluting stent implantation for de novo and in-stent restenosis lesions (Article)

2004-01-01T00:00:00Z

AIMS: The aim of this study is to compare the efficacy of sirolimus-eluting stents (SES) on neointimal growth and vessel remodelling for in-stent restenosis versus de novo coronary artery lesions using serial intravascular ultrasound (IVUS). METHODS AND RESULTS: The study population consisted of 86 patients with in-stent restenosis (ISR) (n=41) or de novo lesions (n=45) treated with SES and evaluated by IVUS post-procedure and at follow-up. One 18-mm SES was used for de novo lesions while 16 patients with ISR received >1SES (total stented length 17.9 mm vs 22.0 mm respectively; P=0.004). At follow-up, no differences were observed between the ISR and de novo groups with respect to changes in the mean external elastic membrane (1.7% vs 1.3%; P=0.53), plaque behind the stent (1.2% vs 3.4%; P=0.49), and lumen areas (0.7% vs 1.9%; P=0.58). No positive remodelling or edge effect was observed. A gap between stents was observed in two patients with ISR, where more prominent, though non-obstructive, neointimal proliferation was noted. CONCLUSION: Sirolimus-eluting stenting is equally effective at inhibiting neointimal proliferation in de novo and ISR lesions without inducing edge restenosis or positive vascular remodelling.

Sirolimus-eluting stent implantation in ST-elevation acute myocardial infarction: a clinical and angiographic study. (Article)

2003-10-21T00:00:00Z

BACKGROUND: Sirolimus-eluting stents (SES) have recently been proven to reduce restenosis and reintervention compared with bare stents. Safety and effectiveness of SES in acute myocardial infarction remain unknown. METHODS AND RESULTS: Since April 16, 2002, a policy of routine SES implantation has been instituted in our hospital, with no clinical or anatomic restrictions, as part of the RESEARCH (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry. During 6 months of enrollment, 96 patients with ST-elevation acute myocardial infarction underwent percutaneous recanalization and SES implantation; these patients comprise the study population. The incidence of major adverse cardiac events (death, nonfatal myocardial infarction, reintervention) was evaluated. Six-month angiographic follow-up was scheduled per protocol. At baseline, diabetes mellitus was present in 12.5% and multivessel disease in 46.9%. Primary angioplasty was performed in 89 patients (92.7%). Infarct location was anterior in 41 (42.7%) of the cases, and 12 patients (12.5%) had cardiogenic shock. Postprocedural TIMI-3 flow was achieved in 93.3% of the cases. In-hospital mortality was 6.2%. One patient (1.1%) had reinfarction and target lesion reintervention the first day as a result of distal dissection and acute vessel occlusion. During follow-up (mean follow-up of 218+/-75 days), 1 patient died (1.1%), no patient had recurrent myocardial infarction, and there were no additional reinterventions. No early or late stent thromboses were documented. At angiographic follow-up (70%), late loss was -0.04+/-0.25, and no patient presented angiographic restenosis. CONCLUSIONS: In this study, sirolimus-eluting stent implantation for patients with ST-elevation acute myocardial infarction was safe without documented angiographic restenosis at 6 months.

Impact of different anatomical patterns of left main coronary stenting on long-term survival. (Article)

2003-09-15T00:00:00Z

Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients

Sonotherapy; antirestenotic therapeutic ultrasound in coronary arteries: the first clinical experience. (Article)

2003-09-01T00:00:00Z

We studied the safety and feasibility of intracoronary sonotherapy (IST) and its effect on the coronary vessel at 6 months. Thirty-seven patients with stable or unstable angina were included (40 lesions). The indication was de novo lesion (n = 26), restenosis (n = 2), in-stent restenosis (n = 11), and a total occlusion of a venous bypass graft. After successful angioplasty, IST was performed using a 5 Fr catheter with three serial ultrasound transducers operating at 1 MHz. IST was successfully performed in 36 lesions (success rate, 90%). IST exposure time per lesion was 718 ± 127 sec. During hospital stay, one patient died due to a bleeding complication. At 6-month follow-up, one patient experienced acute myocardial infarction, eight patients underwent repeat PTCA. No patient underwent CABG. Late lumen loss was 1.05 ± 0.70 mm with a restenosis rate of 25%. IVUS analysis revealed a neointima burden of 25% ± 11%. IST can be applied safely and with high acute procedural success. Sonotherapy-related major adverse events were not observed. Late lumen loss and neointimal growth were similar to conventional PTCA approaches. These results justify the initiation of randomized clinical efficacy studies.

Coronary restenosis after sirolimus-eluting stent implantation: morphological description and mechanistic analysis from a consecutive series of cases. (Article)

2003-07-22T00:00:00Z

BACKGROUND: We describe the clinical and morphological patterns of restenosis after sirolimus-eluting stent (SES) implantation. METHODS AND RESULTS: From 121 patients with coronary angiography obtained >30 days after SES implantation, restenosis (diameter stenosis >50%) was identified in 19 patients and 20 lesions (located at the proximal 5-mm segment in 30% or within the stent in 70%). Residual dissection after the procedure or balloon trauma outside the stent was identified in 83% of the proximal edge lesions. Lesions within the stent were focal, and stent discontinuity was identified in some lesions evaluated by intravascular ultrasound. CONCLUSIONS: Sirolimus-eluting stent edge restenosis is frequently associated with local trauma outside the stent. In-stent restenosis occurs as a localized lesion, commonly associated with a discontinuity in stent coverage. Local conditions instead of intrinsic drug-resistance to sirolimus are likely to play a major role in post-SES restenosis.

TAXUS III Trial: In-Stent Restenosis Treated With Stent-Based Delivery of Paclitaxel Incorporated in a Slow-Release Polymer Formulation (Article)

2003-02-04T00:00:00Z

BACKGROUND: The first clinical study of paclitaxel-eluting stent for de novo lesions showed promising results. We performed the TAXUS III trial to evaluate the feasibility and safety of paclitaxel-eluting stent for the treatment of in-stent restenosis (ISR). METHODS AND RESULTS: The TAXUS III trial was a single-arm, 2-center study that enrolled 28 patients with ISR meeting the criteria of lesion length < or =30 mm, 50% to 99% diameter stenosis, and vessel diameter 3.0 to 3.5 mm. They were treated with one or more TAXUS NIRx paclitaxel-eluting stents. Twenty-five patients completed the angiographic follow-up at 6 months, and 17 of these underwent intravascular ultrasound (IVUS) examination. No subacute stent thrombosis occurred up to 12 months, but there was one late chronic total occlusion, and additional 3 patients showed angiographic restenosis. The mean late loss was 0.54 mm, with neointimal hyperplasia volume of 20.3 mm3. The major adverse cardiac event rate was 29% (8 patients; 1 non-Q-wave myocardial infarction, 1 coronary artery bypass grafting, and 6 target lesion revascularization [TLR]). Of the patients with TLR, 1 had restenosis in a bare stent implanted for edge dissection and 2 had restenosis in a gap between 2 paclitaxel-eluting stents. Two patients without angiographic restenosis underwent TLR as a result of the IVUS assessment at follow-up (1 incomplete apposition and 1 insufficient expansion of the stent). CONCLUSIONS: Paclitaxel-eluting stent implantation is considered safe and potentially efficacious in the treatment of ISR. IVUS guidance to ensure good stent deployment with complete coverage of target lesion may reduce reintervention.

Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience. (Article)

2003-01-15T00:00:00Z

The treatment of ISR remains a therapeutic challenge, since many pharmacological and mechanical approaches have shown disappointing results. The SESs have been reported to be effective in de-novo coronary lesions.

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

2002-09-24T00:00:00Z

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 µg 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.

A new intracoronary measurement catheter, MetriCath, compared to intravascular ultrasound and quantitative coronary angiography in a stented porcine coronary model. (Article)

2002-09-01T00:00:00Z

The purpose of this study was to compare measurements by MetriCath to intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). The MetriCath system consists of a low-pressure (200 mm Hg) balloon catheter connected to a pressure transducer and infusion pump linked to a computer that records pressure-volume curves. Cross-sectional area of blood vessels is obtained directly from the unrestrained and in-stent pressure-volume measurements. We compared stent cross-sectional area measurements by MetriCath, IVUS, and QCA in a porcine stented coronary artery model. Comparison of area measurements in 14 stents showed no significant differences between the three methods (P = 0.66). On average, values differed 0.37 ± 0.60mm2 between MetriCath and QCA, 0.13 ± 0.55 mm2 between MetriCath and IVUS, and 0.22 ± 0.80 mm2 between IVUS and QCA. This corresponds to 6.2% ± 10%, 3.0% ± 9.0%, and 3.1% ± 12.9% relative difference from the average of two corresponding measurements. Linear regression analysis showed excellent correlation between measurements (r ± 0.99 for all comparisons). The differences in in-stent area measurements between MetriCath and both QCA and IVUS were small. Considering the ease and rapidity of obtaining MetriCath results, this technique may form an alternative to the others in evaluating stent expansion. Based on these findings, clinical evaluation seems warranted.

Routine intracoronary beta-irradiation. Acute and one year outcome in patients at high risk for recurrence of stenosis (Article)

2002-07-01T00:00:00Z

AIMS: Intracoronary radiation is a promising therapy potentially reducing restenosis following catheter-based interventions. Currently, only limited data on this treatment are available. The feasibility and outcome in daily routine practice, however, is unknown. METHODS AND RESULTS: In 100 consecutive patients, intracoronary beta-radiation was performed with a (90)Strontium system (Novoste Beta-Cathtrade mark) following angioplasty. Predominantly complex (73% type B2 and C) and long lesions (length 24.3+/-15.3 mm) were included (37% de novo, 19% restenotic and 44% in-stent restenotic lesions). Radiation success was 100%. Mean prescribed dose was 19.8+/-2.5 Gy. A pullback procedure was performed in 19% lesions. Geographic miss occurred in 8% lesions. Periprocedural thrombus formation occurred in four lesions, dissection in nine lesions. During hospital stay, no death, acute myocardial infarction, or repeat revascularization was observed. Major adverse cardiac events occurred predominantly between 6 and 12 months after the index procedure with major adverse cardiac event-free survival of 66% at 12 months (one death, 10 Q-wave myocardial infarctions, 23 target vessel revascularizations; ranked for worst event). CONCLUSION: Routine catheter-based intracoronary beta-radiation therapy after angioplasty is safe and feasible with a high acute procedural success. The clinical 1-year follow-up showed delayed occurrence of major adverse cardiac events between 6 and 12 months after the index procedure

Initial observation regarding changes in vessel dimensions after balloon angioplasty and stenting followed by catheter-based beta-radiation. Is stenting necessary in the setting of catheter-based radiotherapy? (Article)

2002-04-01T00:00:00Z

AIMS: We sought to compare the effect of intracoronary beta-radiation on the vessel dimensions in de novo lesions using three-dimensional intravascular ultrasound quantification after balloon angioplasty and stenting. METHODS AND RESULTS: Forty patients (44 vessels; 28 balloon angioplasty and 16 stenting) treated with catheter-based beta-radiation and 18 non-irradiated control patients (18 vessels; 10 balloon angioplasty and 8 stenting) were investigated by means of three-dimensional volumetric intravascular ultrasound analysis post-procedure and at 6-8 months follow-up. Total vessel (EEM) volume enlarged after both balloon angioplasty and stenting (+37 mm(3) vs +42 mm(3), P=ns), but vessel wall volume (plaque plus media) also increased similarly (+33 mm(3) vs +49 mm(3), P=ns) in the irradiated patients. Lumen volume remained unchanged in both groups (+3 mm(3) vs -7 mm(3), P=ns). In the stent-covered segments, neointima at follow-up was significantly smaller in the irradiated group than the control group (8 mm(3) vs 27 mm(3), P=0.001, respectively), but the total amount of tissue growth was similar in both groups (33 mm(3) vs 29 mm(3), P=ns). CONCLUSIONS: Intracoronary beta-radiation induces vessel enlargement after balloon angioplasty and/or stenting, accommodating tissue growth. Additional stenting may not play an important role in the prevention of constrictive remodelling in the setting of catheter-based intracoronary beta-radiotherapy.

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

2002-02-05T00:00:00Z

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.

Intracoronary beta-radiation to reduce restenosis after balloon angioplasty and stenting; the Beta Radiation In Europe (BRIE) study (Article)

2002-01-01T00:00:00Z

AIMS: The BRIE trial is a registry evaluating the safety and performance of (90)Sr delivered locally (Beta-Cath TM system of Novoste) to de-novo and restenotic lesions in patients with up to two discrete lesions in different vessels. METHODS AND RESULTS: In total, 149 patients (175 lesions) were enrolled; 62 treated with balloons and 113 with stents. The restenosis rate, the minimal luminal diameter and the late loss were determined in three regions of interest: (a) in a subsegment of 5mm containing the original minimal luminal diameter pre-intervention termed target segment; (b) the irradiated segment, 28 mm in length, and (c) the entire analysed segment, 42 mm in length, termed the vessel segment. Binary restenosis was 9.9% for the target segment, 28.9% for the irradiated segment, and 33.6% for the vessel segment. These angiographic results include 5.3% total occlusions. Excluding total occlusions binary restenosis was 4.9%, 25% and 29.9%, respectively. At 1 year the incidence of major adverse cardiac events placed in a hierarchical ranking were: death 2%, myocardial infarction 10.1%, CABG 2%, and target vessel revascularization 20.1%. The event-free survival rate was 65.8%. Non-appropriate coverage of the injured segment by the radioactive source termed geographical miss affected 67.9% of the vessels, and increased edge restenosis significantly (16.3% vs 4.3%, P=0.004). It accounted for 40% of the treatment failures. CONCLUSION: The results of this registry reflect the learning process of the practitioner. The full therapeutic potential of this new technology is reflected by the restenosis rate at the site of the target segment. It can only be unravelled once the incidence of late vessel occlusion and geographical miss has been eliminated by the prolonged use of thienopyridine, the appropriate training of the operator applying this new treatment for restenosis prevention, and the use of longer sources.

Platelet GP IIb/IIIa receptor blockers for failed thrombolysis in acute myocardial infarction, alone or as adjunct to other rescue therapies; single centre retrospective analysis of 548 consecutive patients with acute myocardial infarction (Article)

2002-01-01T00:00:00Z

In order to study the safety of 'rescue' strategies in the treatment of patients with failed thrombolysis, all 548 patients admitted with evolving myocardial infarction to the Thoraxcenter, Rotterdam, from January 1997 until April 1999 were reviewed. Of these patients, 49% had received thrombolysis. Of patients treated with thrombolysis and not referred from other hospitals (n = 154) 36% received rescue therapy for failed thrombolysis. Three rescue therapies were used after failed thrombolysis: percutaneous coronary intervention (74%), retreatment with thrombolysis (39%) and platelet glycoprotein (GP) IIb/IIIa receptor blockers (53%), often in combination. Platelet GP IIb/IIIa receptor blockers were administered in 64% of patients treated with rescue percutaneous coronary intervention. Major bleeding occurred in 14% of all thrombolysis treated patients, and in 30% of patients who received multiple rescue therapies. Bleeding was related to heparin usage and platelet GP IIb/IIIa receptor blockers, as was the insertion of catheters for percutaneous coronary intervention or intra-aortic balloon pumps. Major bleeding resulted in one death due to a ruptured ventricle, one haemorrhagic stroke, and three cases of tamponade for which surgery was needed. Four of these patients had received combination rescue therapy. Rescue therapy is a widely used strategy for failed thrombolysis, but is associated with a high bleeding rate. Alternative reperfusion strategies to avoid failed thrombolysis should be considered in high risk patients.

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

2002-01-01T00:00:00Z

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 microg 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.

Coronary restenosis elimination with a sirolimus eluting stent: first European human experience with 6-month angiographic and intravascular ultrasonic follow-up. (Article)

2001-12-08T00:00:00Z

AIMS: Coronary stenting is limited by a 10%-60% restenosis rate due to neointimal hyperplasia. Sirolimus is a macrocyclic lactone agent that interacts with cell-cycle regulating proteins and inhibits cell division between phases G1 and S1. The hypothesis tested in this study is that local delivery of sirolimus with an eluting stent can prevent restenosis. METHODS AND RESULTS: Fifteen patients were treated with 18 mm sirolimus eluting BX VELOCITY stents. Quantitative angiography and three-dimensional quantitative intravascular ultrasound were performed at implantation and at the 6 months follow-up. All stent implantations were successful. One patient died on day 2, of cerebral haemorrhage and one patient suffered a subacute stent occlusion due to edge dissection (re-PTCA, CKMB 42). At 9 months no further adverse events had occurred and all patients were angina free. Quantitative coronary angiography revealed no change in minimal lumen diameter and percent diameter stenosis and hence no in-lesion or in-stent restenosis. Quantitative intravascular ultrasound showed that intimal hyperplasia volume and percent obstruction volume at follow-up were negligible at 5.3 mm(3)and 1.8%, respectively. No edge effect was observed in the segments proximal and distal to the stents. CONCLUSION: Implantation of a sirolimus-eluting stent seems to effectively prevent intimal hyperplasia.

The pattern of restenosis and vascular remodelling after cold-end radioactive stent implantation. (Article)

2001-08-22T00:00:00Z

Background Edge restenosis is a major problem after radioactive stenting. The cold-end stent has a radioactive mid-segment (15·9mm) and non-radioactive proximal and distal 5·7mm segments. Conceptually this may negate the impact of negative vascular remodelling at the edge of the radiation. Method and Results ECG-gated intravascular ultrasound with three-dimensional reconstruction was performed post-stent implantation and at the 6-month follow-up to assess restenosis within the margins of the stent and at the stent edges in 16 patients. Angiographic restenosis was witnessed in four patients, all in the proximal in-stent position. By intravascular ultrasound in-stent neointimal hyperplasia, with a >50% stented cross-sectional area, was seen in eight patients. This was witnessed proximally (n=2), distally (n=2) and in both segments (n=4). Echolucent tissue, dubbed the ‘black hole’ was seen as a significant component of neointimal hyperplasia in six out of the eight cases of restenosis. Neointimal hyperplasia was inhibited in the area of radiation: Δ neointimal hyperplasia=3·72mm3(8·6%); in-stent at the edges of radiation proximally and distally Δ neointimal hyperplasia was 7·9mm3(19·0%) and 11·4mm3(25·6%), respectively (P=0·017). At the stent edges there was no significant change in lumen volume. Conclusions Cold-end stenting results in increased neointimal hyperplasia in in-stent non-radioactive segments.

Long-term clinical outcome after coronary balloon angioplasty: identification of a population at low risk of recurrent events during 17 years of follow-up. (Article)

2001-07-20T00:00:00Z

AIMS: This study reports the clinical outcome, up to 17 years, of the first 856 consecutive patients treated by coronary angioplasty at a single centre and attempts to identify a subgroup of patients at low risk of adverse events. METHODS AND RESULTS: Follow-up status was established via hospital and general practitioner records and the civil registry. Median follow-up was 16 years. The overall 5-, 10-, 15- and 17-year survival was 90%, 78%, 64% and 58%, respectively and corresponding event-free survival was 53%, 33%, 22% and 19%. After 32% of patients had experienced a major adverse cardiac event in the first year, the annual coronary re-intervention incidence thereafter and, even beyond year 10, remained at 2%--3%. Using multivariable Cox regression, significant independent predictors of mortality were advanced age, diabetes, multivessel disease and impaired left ventricular function at the time of PTCA. A subgroup of 26% of the patients with none of these risk factors had a survival rate similar to the general Dutch population matched for age and gender (at 5 years: 96%, at 10 years: 89% and at 15 years: 83%). CONCLUSION: Although the majority of patients (>80%) experienced a further cardiac event during the 17 years after their first angioplasty procedure, in those non-diabetics under 60 years with single-vessel disease and good left ventricular function, prognosis was similar to the general population.

Clinical and angiographical follow-up after implantation of a 6--12 microCi radioactive stent in patients with coronary artery disease. (Article)

2001-07-19T00:00:00Z

AIMS: This study is the contribution by the Thoraxcenter, Rotterdam, to the European(32)P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease. METHODS AND RESULTS: The radioactivity of the stent at implantation was 6--12 microCi. All patients received aspirin indefinitely and either ticlopidine or clopidogrel for 3 months. Quantitative coronary angiography measurements of both the stent area and the target lesion (stent area and up to 5 mm proximal and distal to the stent edges) were performed pre- and post-procedure and at the 5-month follow-up. Forty-two radioactive stents were implanted in 40 patients. Treated vessels were the left anterior descending coronary artery (n=20), right coronary artery (n=10) or left circumflex artery (n=10). Eight patients received additional non-radioactive stents. Lesion length measured 10+/-3 mm with a reference diameter of 3.07+/-0.69 mm. Minimal lumen diameter increased from 0.98+/-0.53 mm pre-procedure to 2.29+/-0.52 mm (target lesion) and 2.57+/-0.44 mm (stent area) post-procedure. There was one procedural non-Q wave myocardial infarction, due to transient thrombotic closure. Thirty-six patients returned for angiographical follow-up. Two patients had a total occlusion proximal to the radioactive stent. Of the patent vessels, none had in-stent restenosis. Edge restenosis was observed in 44%, occurring predominantly at the proximal edge. Target lesion revascularization was performed in 10 patients and target vessel revascularization in one patient. No additional clinical end-points occurred during follow-up. The minimal lumen diameter at follow-up averaged 1.66+/-0.71 mm (target lesion) and 2.12+/-0.72 (stent area); therefore late loss was 0.63+/-0.69 (target lesion) and 0.46+/-0.76 (stent area), resulting in a late loss index of 0.65+/-1.15 (target lesion) and 0.30+/-0.53 (stent area). CONCLUSION: These results indicate that the use of radioactive stents is safe and feasible, however, the high incidence of edge restenosis makes this technique currently clinically non-applicable.

Relationship Between Neointimal Thickness and Shear Stress After Wallstent Implantation in Human Coronary Arteries. (Article)

2001-01-01T00:00:00Z

Background—In-stent restenosis by excessive intimal hyperplasia reduces the long-term clinical efficacy of coronary stents. Because shear stress (SS) is related to plaque growth in atherosclerosis, we investigated whether variations in SS distribution are related to variations in neointima formation. Methods and Results—In 14 patients, at 6-month follow-up after coronary Wallstent implantation, 3D stent and vessel reconstruction was performed with a combined angiographic and intravascular ultrasound technique (ANGUS). The bare stent reconstruction was used to calculate in-stent SS at implantation, applying computational fluid dynamics. The flow was selected to deliver an average SS of 1.5 N/m2. SS and neointimal thickness (Th) values were obtained with a resolution of 90° in the circumferential and 2.5 mm in the longitudinal direction. For each vessel, the relationship between Th and SS was obtained by linear regression analysis. Averaging the individual slopes and intercepts of the regression lines summarized the overall relationship. Average Th was 0.44±0.20 mm. Th was inversely related to SS: Th=(0.59±0.24)-(0.08±0.10)xSS (mm) (P<0.05). Conclusions—These data show for the first time in vivo that the Th variations in Wallstents at 6-month follow-up are inversely related to the relative SS distribution. These findings support a hemodynamic mechanism underlying in-stent neointimal hyperplasia formation.

Three dimensional intravascular ultrasonic assessment of the local mechanism of restenosis after balloon angioplasty (Article)

2001-01-01T00:00:00Z

OBJECTIVE: To assess the mechanism of restenosis after balloon angioplasty. DESIGN: Prospective study. PATIENTS: 13 patients treated with balloon angioplasty. INTERVENTIONS: 111 coronary subsegments (2 mm each) were analysed after balloon angioplasty and at a six month follow up using three dimensional intravascular ultrasound (IVUS). MAIN OUTCOME MEASURES: Qualitative and quantitative IVUS analysis. Total vessel (external elastic membrane), plaque, and lumen volume were measured in each 2 mm subsegment. Delta values were calculated (follow up - postprocedure). Remodelling was defined as any (positive or negative) change in total vessel volume. RESULTS: Positive remodelling was observed in 52 subsegments while negative remodelling occurred in 44. Remodelling, plaque type, and dissection were heterogeneously distributed along the coronary segments. Plaque composition was not associated with changes in IVUS indices, whereas dissected subsegments had a greater increase in total vessel volume than those without dissection (1.7 mm(3) v -0.33 mm(3), p = 0.04). Change in total vessel volume was correlated with changes in lumen (p < 0.05, r = 0.56) and plaque volumes (p < 0.05, r = 0.64). The site with maximum lumen loss was not the same site as the minimum lumen area at follow up in the majority (n = 10) of the vessels. In the multivariate model, residual plaque burden had an influence on negative remodelling (p = 0.001, 95% confidence interval (CI) -0.391 to -0.108), whereas dissection had an effect on total vessel increase (p = 0.002, 95% CI 1.168 to 4.969). CONCLUSIONS: The mechanism of lumen renarrowing after balloon angioplasty appears to be determined by unfavourable remodelling. However, different patterns of remodelling may occur in individual injured coronary segments, which highlights the complexity and influence of local factors in the restenotic process.

Radioactive stents delay but do not prevent in-stent neointimal hyperplasia (Article)

2001-01-01T00:00:00Z

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.

"Edge Effect" of 32P Radioactive Stents Is Caused by the Combination of Chronic Stent Injury and Radioactive Dose Falloff (Article)

2001-01-01T00:00:00Z

BACKGROUND: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side. METHODS AND RESULTS: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01). CONCLUSIONS: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.

Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress distribution. (Article)

2000-10-01T00:00:00Z

Mechanisms of in-stent restenosis are not fully understood. Shear stress is known to play a role in plaque and thrombus formation and is sensitive to changes in regional vessel geometry. Hence, we evaluated the regional changes in 3-D geometry and shear stress induced by stent placement in coronary arteries of pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D geometry was used to calculate locally the curvature, while the shear stress distribution was obtained by computational fluid dynamics. Local changes in shear stress were obtained at the entrance and exit of the stent for baseline (0. 65+/-0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent implantation, the curvature increased by 121% at the entrance and by 100% at the exit of the stent, resulting in local changes in shear stress. In general, at the entrance of the stent local maxima in shear stress were generated, while at the exit both local maxima and minima in shear stress were observed (p<0.05). Additionally, the shear stress at the entrance and exit of the stent were correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation changes 3-D vessel geometry in such a way that regions with decreased and increased shear stress occur close to the stent edges. These changes might be related to the asymmetric patterns of in-stent restenosis.

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

2000-01-01T00:00:00Z

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 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. Conclusions—Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting.

True 3-Dimensional Reconstruction of Coronary Arteries in Patients by Fusion of Angiography and IVUS (ANGUS) and Its Quantitative Validation (Article)

2000-01-01T00:00:00Z

Background—True 3D reconstruction of coronary arteries in patients based on intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS information (ANGUS). The clinical applicability of ANGUS was tested, and its accuracy was evaluated quantitatively. Methods and Results—In 16 patients who were investigated 6 months after stent implantation, a sheath-based catheter was used to acquire IVUS images during an R-wave–triggered, motorized stepped pullback. First, a single set of end-diastolic biplane angiographic images documented the 3D location of the catheter at the beginning of pullback. From this set, the 3D pullback trajectory was predicted. Second, contours of the lumen or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular rotation of the reconstruction was optimized by quantitative matching of the silhouettes of the 3D reconstruction with the actual biplane images. Reconstructions were obtained in 12 patients. The number of pullback steps, which determines the pullback length, closely agreed with the reconstructed path length (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions showed high correlation (0.84 to 0.97) with corresponding measurements in the actual biplane angiographic images. Conclusions—With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.

Residual Plaque Burden, Delivered Dose, and Tissue Composition Predict 6-Month Outcome After Balloon Angioplasty and Beta-Radiation Therapy (Article)

2000-01-01T00:00:00Z

Background—Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with ß-radiation after BA. Methods and Results—Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a ß-emitting 90Sr/90Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (Dv90Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). Dv90Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r=0.71; P=0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, Dv90Adv, and type of plaque. Conclusions—Residual plaque burden, delivered dose, and tissue composition play a fundamental role in the volumetric outcome at 6-month follow-up after ß-radiation therapy and BA.

Geographic Miss (Article)

2000-01-01T00:00:00Z

Background—A recognized limitation of endovascular ß-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 ß-radiation. Methods and Results—We analyzed 50 consecutive patients treated with ß-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 ß-radiation induces deleterious outcome.

Outcome from balloon induced coronary artery dissection after intracoronary beta radiation (Article)

2000-01-01T00:00:00Z

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 dissection. No change in anginal status was seen despite the presence of unhealed dissection. CONCLUSION: beta 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.

Biocompatibility of phosphorylcholine coated stents in normal porcine coronary arteries (Article)

2000-01-01T00:00:00Z

OBJECTIVE: To improve the biocompatibility of stents using a phosphorylcholine coated stent as a form of biomimicry. INTERVENTIONS: Implantation of phosphorylcholine coated (n = 20) and non-coated (n = 21) stents was performed in the coronary arteries of 25 pigs. The animals were killed after five days (n = 6), four weeks (n = 7), and 12 weeks (n = 8), and the vessels harvested for histology, scanning electron microscopy, and morphometry. MAIN OUTCOME MEASURES: Stent performance was assessed by studying early endothelialization, neointima formation, and vessel wall reaction to the synthetic coating. RESULTS: Stent thrombosis did not occur in either group. Morphometry showed no significant differences between the two study groups at any time point. At five days both the coated and non-coated stents were equally well endothelialised (91% v 92%, respectively). At four and 12 weeks there was no difference in intimal thickness between the coated and non-coated stents. Up to 12 weeks postimplant the phosphorylcholine coating was still discernible in the stent strut voids, and did not appear to elicit an adverse inflammatory response. CONCLUSION: In this animal model the phosphorylcholine coating showed excellent blood and tissue compatibility, unlike a number of other polymers tested in a similar setting. Given that the coating was present up to 12 weeks postimplant with no adverse tissue reaction, it may be a potential candidate polymer for local drug delivery.

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

2000-01-01T00:00:00Z

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.

Residual plaque burden, delivered dose, and tissue composition predict 6-month outcome after balloon angioplasty and beta-radiation therapy (Article)

2000-01-01T00:00:00Z

BACKGROUND: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with beta-radiation after BA. METHODS AND RESULTS: Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a beta-emitting (90)Sr/(90)Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (D(v90)Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). D(v90)Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r = 0.71; P = 0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, D(v90)Adv, and type of plaque. CONCLUSIONS: Residual plaque burden, delivered dose, and tiss composition play a fundamental role in the volumetric outcome at 6-month follow-up after beta-radiation therapy and BA.

Inhibition of restenosis with beta-emitting radiotherapy: Report of the Proliferation Reduction with Vascular Energy Trial (PREVENT) (Article)

2000-01-01T00:00:00Z

BACKGROUND: Intracoronary gamma- and beta-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of beta-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. METHODS AND RESULTS: A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the beta-emitting (32)P 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: beta-radiotherapy with a centered (32)P 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.

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

2000-01-01T00:00:00Z

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.

Comparison of brachytherapy strategies based on dose-volume histograms derived from quantitative intravascular ultrasound. (Article)

1999-04-01T00:00:00Z

PURPOSE: We present in this paper the comparison, by simulation, of different treatment strategies based either on beta- or gamma-sources, both with and without a centering device. Ionizing radiation to prevent restenosis is an emerging modality in interventional cardiology. Numerous clinical studies are presently being performed or planned, but there is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of possible dose distributions over the arterial vessel wall. This paper discusses the potential merits of dose-volume histograms (DVH) based on three-dimensional (3-D) reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) to compare brachytherapy treatment strategies. MATERIALS AND METHODS: DVH describe the cumulative distribution of dose over three specific volumes: (1) at the level of the luminal surface, a volume was defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface; (2) at the level of the IVUS echogenic media-adventitia interface (external elastic lamina [EEL]), an adventitial volume was computed considering a 0.5-mm thickness from EEL; and (3) the volume encompassed between the luminal surface and the EEL (plaque + media). The IVUS data used were recorded in 23 of 31 patients during the Beta Energy Restenosis Trial (BERT) conducted in our institution. RESULTS: On average, the minimal dose in 90% of the adventitial volume was 37 +/- 16% of the prescribed dose; the minimal dose in 90% of the plaque + media volume was 58 +/- 24% and of the luminal surface volume was 67 +/- 31%. The minimal dose in the 10% most exposed luminal surface volume was 296 +/- 42%. Simulations of the use of a gamma-emitter and/or a radioactive source train centered in the lumen are reported, with a comparison of the homogeneity of the dose distribution.

Long term outcome after coronary stent implantation: a 10 year single centre experience of 1000 patients (Article)

1999-01-01T00:00:00Z

OBJECTIVE: To describe the long term clinical outcome (up to 11 years) after coronary stenting. DESIGN: A single centre observational study encompassing 1000 consecutive patients with a first stent implantation (1560 stents) between 1986 and 1996, who were followed for at least one year with a median follow up of 29 months (range 12-132 months). RESULTS: Up to July 1997 the cumulative incidence of the major adverse cardiac events (MACE) of death, non-fatal acute myocardial infarction, coronary artery bypass grafting, and repeat percutaneous transluminal coronary angioplasty was 8.2%, 12.8%, 13.1%, and 22.4%, respectively. Survival at one, three, and five years was 95%, 91%, and 86%, respectively. Comparison of MACE incidence during the "anticoagulant era" and the "ticlopidine era" revealed significantly improved event free survival with ticlopidine (27% v 13%; p < 0.005). Multivariable analyses showed that ejection fraction < 50% (relative risk (RR) 4. 1), multivessel disease (RR 3.0), diabetes (RR 2.9), implantation in saphenous vein graft (RR 2.1), indication for unstable angina (RR 1. 9), and female sex (RR 1.7) were independent predictors of increased mortality after stenting. Independent predictors of any MACE were multivessel stenting (RR 2.0), implantation in saphenous bypass graft (RR 1.6), diabetes (RR 1.5), anticoagulant treatment (versus ticlopidine and aspirin) (RR 1.5), bailout stenting (RR 1.5), multivessel disease (RR 1.4), and multiple stent implantation (RR 1. 5). CONCLUSIONS: Long term survival and infarct free survival was good, particularly in non-diabetic men with single vessel disease and good ventricular function, who had a single stent implanted in a native coronary artery. A dramatic improvement was observed in event free survival, both early and late, with the replacement of anticoagulation by ticlopidine. This, of course, cannot be separated from improved stent implantation techniques between 1986 and 1995. Ultimately, almost 40% of the patients experienced an adverse cardiac event (mainly repeat intervention) in the long term. New advances in restenosis treatments and in secondary prevention must be directed at this aspect of patient management after stenting.

Intracoronary ultrasound longitudinal reconstruction of a postangioplasty coronary artery dissection (Article)

1999-01-01T00:00:00Z

Late coronary occlusion after intracoronary brachytherapy (Article)

1999-01-01T00:00:00Z

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.

Geometric vascular remodeling after balloon angioplasty and beta-radiation therapy: A three-dimensional intravascular ultrasound study (Article)

1999-01-01T00:00:00Z

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.

Preserved endothelium-dependent vasodilation in coronary segments previously treated with balloon angioplasty and intracoronary irradiation (Article)

1999-01-01T00:00:00Z

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 stable patients at 6-month follow-up. This functional response appeared to be better than those documented both in the distal segments and in segments treated with BA alone.

beta-Particle-emitting radioactive stent implantation. A safety and feasibility study (Article)

1999-01-01T00:00:00Z

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.

Coronary wallstents show significant late, postprocedural expansion despite implantation with adjunct high-pressure balloon inflations. (Article)

1998-07-15T00:00:00Z

Adjunct high-pressure balloon inflations following the delivery of oversized self-expandable Wallstents may affect their implied late, postprocedural self-expansion. Consequently, we examined 15 "Magic" Wallstents, which were implanted following a strategy of stent oversizing and subsequent adjunct high-pressure balloon inflations (16 +/- 2 atm; all > or = 12 atm). The excellent radiographic visibility of this stent permitted reliable quantitative coronary angiographic measurement of both lumen and stent dimensions (before and after stenting, and at follow-up). At follow-up, extent and distribution of in-stent neointimal proliferation were evaluated with volumetric intravascular ultrasound. Between postintervention and follow-up examination, mean stent diameter increased from 3.7 +/- 0.4 to 4.2 +/- 0.4 mm (p <0.0001); there was no significant difference in late stent expansion between proximal, mid-, and distal stent subsegments. Late stent expansion showed a significant (reverse) relation to maximum balloon size (r = -0.56, p <0.04), but not with follow-up lumen size or late lumen loss. On average, 52 +/- 18% of the stent was filled with neointimal ingrowth; neointimal volume/cm stent length was 64 +/- 22 mm3. Both late stent expansion (r = 0.36, p <0.02) and maximum balloon pressure (r = 0.41, p <0.001) were related to neointimal volume/cm stent but not to follow-up lumen size. Thus, despite high-pressure implantation, Wallstents showed significant late self-expansion, which resulted in larger stent dimensions at follow-up that assisted in accommodating in-stent neointimal proliferation. Conversely, late stent expansion had a significant relation to the extent of in-stent neointimal ingrowth. Beneficial and disadvantageous effects of the late stent expansion appear to be balanced, because a relation to late lumen loss or follow-up lumen dimensions was not found to be present.

Variations of remodeling in response to left main atherosclerosis assessed with intravascular ultrasound in vivo. (Article)

1997-12-01T00:00:00Z

Histopathologic studies have demonstrated that vessels enlarge to compensate for an increase in plaque burden; this has been confirmed in vivo using intravascular ultrasound (IVUS). The initial studies suggested a biphasic course of lesion formation with (1) preservation of lumen dimensions up to a plaque burden of approximately 40%, and (2) luminal narrowing as plaque burden further increases. In this study, we used IVUS and angiography to assess the extent of left main (LM) atherosclerosis in 107 patients undergoing catheter-based procedures of the left anterior descending or left circumflex coronary arteries. Using IVUS, atherosclerotic plaques were found in all LM arteries, but only 26 (24%) had varying degrees of luminal narrowing on the angiogram. Nevertheless, there was an inverse relation (r = −0.62, p <0.0001) between the minimal lumen area and the plaque burden (i.e., plaque + media divided by total vessel area) that was not restricted to plaque burden values >40% (or >30%), but persisted at plaque burden values of 20% to 40%. In addition, LM arteries with a plaque burden <40% had a similar total vessel area as did LM arteries with a plaque burden ≥40% (22.9 ± 6.1 vs 21.8 ± 4.8 mm2, p = 0.30). These data suggest that lumen dimensions may not be preserved even if plaque occupies no more than 20% to 40% of the total vessel area. Thus, there is more variation in remodeling response during earlier stages of plaque accumulation within the LM artery than is commonly suggested.

A word of caution on optimizing stent deployment in calcified lesions: acute coronary rupture with cardiac tamponade. (Article)

1996-01-25T00:00:00Z

Beta-particle-emitting stents radiate enthusiasm in the search for effective prevention of restenosis. (Article)

1996-01-01T00:00:00Z

Renarrowing of a coronary artery (restenosis) at the site of earlier balloon angioplasty is in 1996 still a clinical problem, with an incidence of 30% to 50%. Despite 20 years of experimental and clinical research, the biology of restenosis is still not fully understood. These studies have, however, greatly enhanced our insight into the restenosis process. The most widely accepted concept is that restenosis is the result of the vascular healing response to the injurious treatment. This response includes several phases: elastic recoil, thrombosis, inflammation, proliferation, and organization (or remodeling). Application of therapies aimed at reducing restenosis according to this paradigm has been partially successful. One approach involves the limitation of the thrombotic phase by effectively blocking the platelet glycoprotein IIb/ IIIa receptor1 (preliminary results from the CAPTURE and EPILOG studies support this approach). In these studies, the need for repeated coronary revascularization was substantially reduced but not eliminated. A second approach is the use of coronary stents. By limiting the residual lesion, elastic recoil, and late remodeling, stents reduce the need for both revascularization and angiographic restenosis2 3 compared with balloon angioplasty.

Reduction in Thrombotic Events With Heparin-Coated Palmaz-Schatz Stents in Normal Porcine Coronary Arteries. (Article)

1996-01-01T00:00:00Z

Background The use of stents improves the result after balloon coronary angioplasty. Thrombogenicity of stents is, however, a concern. In the present study, we compared stents with an antithrombotic coating with regular stents. Methods and Results Regular stents were placed in coronary arteries of pigs receiving no aspirin (group 1; n=8) or aspirin over 4 weeks (group 2, n=10) or 12 weeks (group 3, n=9). Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4). The other animals received aspirin and coated stents with a heparin activity of 12 pmol antithrombin III/stent (group 5, n=10) or 20 pmol/stent (group 6, n=10; group 7, n=10). Quantitative arteriography was performed at implantation and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an additional 5 animals, five regular and five coated stents (20 pmol/stent) were placed and explanted after 5 days for examination of the early responses to the implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups 1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin-coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P<.001). Histological analysis at 4 weeks showed that the neointima in group 6 was thicker compared with its control group 2 (259±104 and 117±36 µm, P<.01), but at 12 weeks the thickness was similar (152±61 and 198±49 µm, respectively). Comparison at 5 days suggested delayed endothelialization of the coating.

Heparin-coated Palmaz-Schatz Stents in Human Coronary Arteries. . (Article)

1996-01-01T00:00:00Z

Background The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. Methods and Results The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo lesion in whom heparin-coated stent implantation was attempted, implantation was successful in 202 patients (98%). Stent thrombosis did not occur during all four phases, and the overall clinical success rate at discharge was 99%. Bleeding complications requiring blood transfusion or surgery fell from 7.9% in phase I to 5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2, and 3.1 days for the consecutive phases. The restenosis rate for the combined four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6 months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively, were event free. For the four phases, the event-free rate was 86%, which compares favorably with the rate observed in the Benestent-I study (80%; relative risk, 0.68 [0.45 to 1.04]). Conclusions The implantation of stents coated with polyamine and end-point–attached heparin in stable patients with one significant de novo coronary lesion is well tolerated, is associated with no (sub)acute stent thrombosis, and results in a favorable event-free survival after 6 months.

Intracoronary Heparin Delivery in Humans (Article)

1995-01-01T00:00:00Z

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 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.

Stenting or balloon angioplasty of stenosed autologous saphenous vein grafts in pigs (Article)

1994-01-01T00:00:00Z

Coronary stent coatings (Article)

1994-01-01T00:00:00Z

Benestent II: Back to the future (Article)

1994-01-01T00:00:00Z

It has been shown repeatedly in animal and clinical studies that heparin coating reduces thrombotic complications of several surfaces in contact with flowing blood. The demonstration that implantation of heparin-coated coronary stents is also effective in prevention of subacute thrombotic occlusion in a pig model offers the perspective of a clinical role of this treatment too. In order to put this to the test, the Benestent II pilot trial has been designed. This study will be conducted in a stepwise fashion in order to explore the feasibility of delaying deep anticoagulation as much as possible. Therefore, the primary goal is to minimize or exclude the need for heparin treatment following stent implantation. In addition, the effects on the need for revascularization procedures during follow-up will be recorded as well as the late morphological consequences as measured with quantitative coronary angiography.

Histology after stenting of human saphenous vein bypass grafts: observations from surgically excised grafts 3 to 320 days after stent implantation (Article)

1993-01-01T00:00:00Z

OBJECTIVES. To gain insight into the mechanism of stenting in humans and its short- and long-term implications, we studied the vascular wall of saphenous vein aortocoronary bypass grafts after implantation of the Wallstent. BACKGROUND. The implantation of a stent in aortocoronary bypass grafts may provide an alternative solution for revascularization in patients who are poor candidates for reoperation. Because human histopathologic findings after stenting with the Wallstent have not previously been described in detail, we examined graft segments that were surgically retrieved from 10 patients (21 stents) at 3 days to 10 months after implantation of the stent. METHODS. The grafts were examined by a combination of the following techniques: light microscopy, immunocytochemistry and both scanning and transmission electron microscopy. RESULTS. Early observations revealed that large amounts of platelets and leukocytes adhered to the stent wires during the first few days. At 3 months, the wires were embedded in a layered new intimal thickening, consisting of smooth muscle cells in a collagenous matrix. In addition, foam cells were abundant near the wires. Extracellular lipids and cholesterol crystals were found after 6 months. Smooth muscle cells and extracellular matrix formed the predominant component of restenosis. This new intimal thickening was lined with endothelium, in some cases showing defect intercellular junctions and abnormal adherence of leukocytes and platelets as late as 10 months after implantation. CONCLUSIONS. This type of stent is potentially thrombogenic and seems to be associated with extracellular lipid accumulation in venous aortocoronary bypass grafts.

Can the same edge-detection algorithm be applied to on-line and off-line analysis systems? Validation of a new cinefilm-based geometric coronary measurement software (Article)

1993-01-01T00:00:00Z

In the Cardiovascular Measurement System (CMS) the edge-detection algorithm, which was primarily designed for the Philips digital cardiac imaging system (DCI), is applied to cinefilms. Comparative validation of CMS and DCI was performed in vitro and in vivo with intracoronary insertion of stenosis phantoms in anesthetized pigs. The "obstruction diameter" (OD) was measured at the artificial stenoses visualized by angiography with calibration at the isocenter (ISO) and catheter calibration (CATH) and compared with the true phantom diameters. A clinical comparison of OD, reference diameter (RD), and percentage diameter stenosis (DS) was performed on 70 corresponding images from post-PTCA angiograms. In vitro, OD (CMS) yielded an accuracy of 0.18 +/- 0.14 mm with 100% (correlation coefficient: r = 0.97, y = 0.06 + 0.75x, standard error of estimate [SEE] = 0.09) and 0.19 +/- 0.15 mm with 50% contrast (r = 0.94, y = 0.02 + 0.81 x). OD (DCI) yielded an accuracy of 0.11 +/- 0.06 mm with 100% (r = 0.99, y = -0.03 + 0.91 x, SEE = 0.05) and 0.24 +/- 0.13 mm with 50% contrast (r = 0.94, y = 0.29 + 6.69 x, SEE = 0.12). In vivo, OD (CMS) yielded an accuracy of 0.18 +/- 0.23 mm with ISO (r = 0.89, y = 0.02 + 0.83 x, SEE = 0.22) and 0.26 +/- 0.24 mm with CATH (r = 0.89, y = 0.06 + 0.72 x, SEE = 0.19). OD (DCI) yielded an accuracy of 0.08 +/- 0.15 mm with ISO (r = 0.96, y = 0.08 + 0.86 x, SEE = 0.14) and 0.18 +/- 0.21 mm with CATH (r = 0.92, y = 0.09 + 0.76 x, SEE = 0.17). The clinical comparison showed reasonable agreement for OD only (r = 0.81, y = 0.26 + 0.81 x, SEE = 0.29). Transformation of an edge-detection algorithm from a digital to a cinefilm-based system can lead to impairment of measurement reliability.

In-vivo validation of on-line and off-line geometric coronary measurements using insertion of stenosis phantoms in procine coronary arteries (Article)

1992-01-01T00:00:00Z

Geometric coronary artery measurements with the Phillips Digital Cardiac Imaging System (DCI) and the Cardiovascular Angiography Analysis System (CAAS) were validated using percutaneous insertion of radiolucent stenosis phantoms in swine coronary arteries. Angiographic visualization of the stenosis lumens (phi 0.5, 0.7, 1.0, 1.4, 1.9 mm) was simultaneously recorded on DCI and cinefilm. The acquisition systems were calibrated by either the diameter of the guiding catheter (catheter CAL) or the isocenter method (isocenter CAL). Minimal luminal diameters (MLD) obtained with CAAS and DCI on 20 corresponding cineframes were compared with the true phantom diameters (PD). The accuracy of MLD measurements with the CAAS using isocenter CAL was -0.07mm, the precision 0.21 mm (r = 0.91; y = 0.30 + 0.79x; SEE = 0.19), with catheter CAL the accuracy was 0.09 mm, the precision 0.23 mm (r = 0.89; y = 0.19 + 0.74x; SEE = 0.19). The accuracy of MLD measurements using the DCI with isocenter CAL was 0.08 mm, the precision 0.15 min (r = 0.96; y = 0.08 + 0.86x; SEE = 0.14), with catheter CAL the accuracy was 0.18 mm, the precision 0.21 mm (r = 0.92; y = 0.09 + 0.76x; SEE = 0.17). DCI underestimated PD with isocenter CAL (p less than 0.05) and with catheter CAL (p less than 0.001). MLD can be measured with high accuracy, both applying on-line digital as well as off-line cineangiographic analysis. The results of digital measurements demonstrate high reliability of the new digital software package.

Development of a polymer endovascular prosthesis and its implantation in porcine arteries (Article)

1992-01-01T00:00:00Z

A polyethylene-terephthalate braided mesh stent has been developed for application in the (coronary) arterial tree. In vitro measurements showed that the radial pressure delivered by this device was in the same range as that of a stainless steel stent. Hysteresis-like behavior, however, occurred after constraining the polyester stent for a period of only 15 minutes on a delivery system for percutaneous implantation. This implies that the polymer stent must be mounted on this delivery system immediately before the placement procedure, and that either a diameter in the unconstrained condition must be selected, which is considerably larger than the diameter of the target vessel, or stent expansion has to be enhanced by balloon expansion. Taking into account the results obtained during the in vitro studies, we investigated the angiographic patency and histologic features after implantation of this polyester stent in peripheral arteries of pigs. In four animals eight stents were placed. Except for heparin during the implantation procedure only, antithrombotic or antiplatelet drugs were not administered. After 4 weeks repeat angiography was performed. Angiography revealed that five of the six correctly placed stents were patent. At autopsy, two additional patent stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative assessment showed that the mean luminal diameters of the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 3.1 +/- 0.3 mm at 4 weeks after implantation. Histology demonstrated an inflammatory reaction of variable severity around the stent fibers. Quantitative histologic measurements showed that the thickness of the neointima was 114 +/- 38 mum after 4 weeks. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. Hysteresis-like behavior of polyester stents, however, influences the selection of the nominal stent diameter as well as the forces exerted to the vessel wall. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at 4 weeks. The extent of neointimal proliferation was similar to that observed after placement of metal stents in swine, despite the presence of a more pronounced inflammatory reaction.

Coronary stenting with a new, radiopaque, balloon-expandable endoprosthesis in pigs (Article)

1991-01-01T00:00:00Z

BACKGROUND. Intracoronary stents may be effective when used as "bail-out" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs. METHODS AND RESULTS. In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks. CONCLUSIONS. Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited.

Stenting of coronary arteries: has a modern Pandora's box been opened (Article)

1991-01-01T00:00:00Z

Interventional cardiology has recently witnessed the growth of several alternatives to percutaneous transluminal angioplasty, including coronary stenting. Although stenting appears to be useful in treating abrupt closure after coronary angioplasty, its effectiveness in limiting the complex processes responsible for late restenosis is much less certain. Pathologic examination of stented human saphenous bypass grafts shows extensive deposits of platelets, fibrin and leukocytes along the stent wires within the 1st week and formation of a neointima of variable thickness after 3 months without evidence of foreign body reaction. The long-term effects of continuous barotrauma induced by the expanded stent remain unknown. It is difficult to assess the relative merits of the new devices, but stenting has several theoretic advantages. It seems less disruptive to the underlying architecture of the vessel wall and enjoys favorable theoretic and effective expansion ratios. Wide-spread clinical acceptance for stenting will depend on demonstrating that its safety, efficacy and cost efficiency are superior to those of balloon angioplasty.

Do stents interfere with the densitometric assessment of a coronary artery lesion (Article)

1991-01-01T00:00:00Z

This in vitro study was designed to assess the contribution of three currently investigated coronary stents to the densitometric measurement of a known stenosis contained within two different sized plexiglass phantoms. These studies were performed at two concentrations of the contrast agent iopamidol (50 and 100%). The calculated minimal luminal cross-sectional area values in the control phantom ranged from 0-18% higher than the theoretical values. Insertion of a stainless steel stent (Wallstent, Schneider, Zurich or Palmaz-Schatz, Johnson and Johnson, Warren, NJ) resulted in further minor increases (less than or equal to 8% in the calculated minimal luminal cross-sectional area, except in the smaller phantom filled with 50% contrast medium. The Wiktor (tantalum) stent (Medtronic, Minneapolis, MN) had the largest impact of the three stents depending on the concentration of iopamidol (100% contrast medium: 9-13% values above control; 50% contrast medium; 23-56% higher). We conclude that although densitometry may overestimate the minimal luminal cross-sectional area in stented vessels, this effect is usually minor with stainless steel stents. However, tantalum-containing stents may result in serious overestimation of lesion area, particularly if contrast is diluted or the vessel is not well filled.

Stenting of coronary arteries. Are we the sorcerer's apprentice? (Article)

1989-01-01T00:00:00Z

Acute effect of cigarette smoking on cardiac prostaglandin synthesis and platelet behavior in patients with coronary heart disease (In Book)

1983-01-01T00:00:00Z