PubMed Health⌕ Search

Biomedical subjects

Ulrich Gerckens

Publications and source records attributed to Ulrich Gerckens.

18 recordsLinked to original sources
PubMed2006

Network analysis of human in-stent restenosis.

BACKGROUND: Recent successes in the treatment of in-stent restenosis (ISR) by drug-eluting stents belie the challenges still faced in certain lesions and patient groups. We analyzed human coronary atheroma in de novo and restenotic disease to identify targets of therapy that might avoid these limitations. METHODS AND RESULTS: We recruited 89 patients who underwent coronary atherectomy for de novo atherosclerosis (n=55) or in-stent restenosis (ISR) of a bare metal stent (n=34). Samples were fixed for histology, and gene expression was assessed with a dual-dye 22,000 oligonucleotide microarray. Histological analysis revealed significantly greater cellularity and significantly fewer inflammatory infiltrates and lipid pools in the ISR group. Gene ontology analysis demonstrated the prominence of cell proliferation programs in ISR and inflammation/immune programs in de novo restenosis. Network analysis, which combines semantic mining of the published literature with the expression signature of ISR, revealed gene expression modules suggested as candidates for selective inhibition of restenotic disease. Two modules are presented in more detail, the procollagen type 1 alpha2 gene and the ADAM17/tumor necrosis factor-alpha converting enzyme gene. We tested our contention that this method is capable of identifying successful targets of therapy by comparing mean significance scores for networks generated from subsets of the published literature containing the terms "sirolimus" or "paclitaxel." In addition, we generated 2 large networks with sirolimus and paclitaxel at their centers. Both analyses revealed higher mean values for sirolimus, suggesting that this agent has a broader suppressive action against ISR than paclitaxel. CONCLUSIONS: Comprehensive histological and gene network analysis of human ISR reveals potential targets for directed abrogation of restenotic disease and recapitulates the results of clinical trials of existing agents.

ADAM Proteins↗
PubMed2006

Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study.

BACKGROUND: The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high-risk comorbid conditions. Therefore, a prospective, single-center, nonrandomized study was performed in high-risk patients with aortic valve disease to evaluate the feasibility and safety of percutaneous implantation of a novel self-expanding aortic valve bioprosthesis (CoreValve). METHODS AND RESULTS: Symptomatic high-risk patients with an aortic valve area <1 cm2 were considered for enrollment. CoreValve implantation was performed under general anesthesia with extracorporeal support using the retrograde approach. Clinical follow-up and transthoracic echocardiography were performed after the procedure and at days 15 and 30 after device implantation to evaluate short-term patient and device outcomes. A total of 25 patients with symptomatic aortic valve stenosis (mean gradient before implantation, 44.2+/-10.8 mm Hg) and multiple comorbidities (median logistic EuroScore, 11.0%) were enrolled. Device success and procedural success were achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device implantation resulted in a marked reduction in the aortic valve gradients (mean gradient after implantation, 12.4+/-3.0 mm Hg; P<0.0001). The mean aortic regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral events occurred in 8 patients (32%), including mortality in 5 patients (20%). Among 18 patients with device success surviving to discharge, no adverse events occurred within 30 days after leaving the hospital. CONCLUSIONS: Percutaneous implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk patients with aortic stenosis with or without aortic regurgitation is feasible and, when successful, results in marked hemodynamic and clinical improvement.

Aged↗
PubMed2006

Use of Taxus polymer-coated paclitaxel-eluting stents for treatment of in-stent restenosis in real world patients: results of clinical and angiographic follow-up at six months in a single-center registry.

OBJECTIVE: To evaluate the safety and efficacy of Taxus paclitaxel-eluting stents in a real world group of unselected patients with coronary in-stent restenosis (ISR) lesions. METHODS: This is a prospective single-center registry of a consecutive series of 94 patients with 104 ISR lesions, without previous brachytherapy, over a period of 1 year. Quantitative coronary angiographic analyses were performed at baseline and at 6-month angiographic follow-up. Clinical follow-up were obtained at 6 months. RESULTS: Pre-intervention mean reference vessel diameter was 2.62 +/- 0.50 mm and mean lesion length was 13.95 +/- 6.78 mm. Baseline ISR patterns were mostly either Type I focal (32.7%) or Type II diffuse intrastent (48.1%). At 6-month angiographic follow-up, the in-stent and in-segment binary restenosis was 3.8% (4/105) and 7.6% (8/105) respectively, and the in-stent and in-segment late loss was 0.30 +/- 0.50 mm and 0.57 +/- 0.54 mm, respectively. Seven of these eight restenosed lesions had a diffuse or proliferative ISR pattern prior to intervention. Lesions that restenosed had longer mean stent length per lesion (37.3 mm vs. 22.5 mm in nonrestenosed group; P = 0.001) and more likely to have had a pattern of total occlusion pre-intervention (25.0% vs. 3.1% in nonrestenosed group; P = 0.046). At 6-month clinical follow-up, the MACE rate was 8.5% and target lesion revascularization rate was 7.4%. There was no death but subacute stent thrombosis occurred in 1 patient (1.1%) at 3 days after intervention. CONCLUSIONS: Paclitaxel-eluting Taxus stent for the treatment of ISR effectively suppresses recurrent neointimal proliferation, and was safe and efficacious at 6-month follow-up.

Aged↗
PubMed2006

[Percutaneous aortic valve replacement].

Surgical aortic valve replacement has been the gold standard for treatment of symptomatic aortic valve disease. However, the success of this approach depends on various patient- and situation-specific risk predictors; thus, the perioperative mortality can reach up to 50%. Percutaneous valve replacement might offer a new less invasive alternative. Since 2002, a balloon-expandable valve prosthesis is under evaluation in symptomatic high-risk patients with aortic valve stenosis. After modifications of both the implantation technique as well as the design of the prosthesis, procedural success rates of > 75% and adverse event rates of < 20% at 30-day follow-up have been reported. A new alternative to this approach is the self-expanding valve prosthesis. The recently reported First-in-Man Study demonstrated the feasibility of this technique. However, the strict inclusion criteria for both procedures limit the number of potential candidates. New devices are currently under development, which will allow for a broader use of percutaneous valve replacement in the near future.

Angiography↗
PubMed2006

Evaluation of a new polymer-coated paclitaxel-eluting stent for treatment of de novo lesions: six-month clinical and angiographic follow-up results of the APPLAUSE trial.

BACKGROUND: This trial assesses the safety and efficacy of the PicoElite stent (amg International GmbH, Raesfeld-Erle, Germany), a new paclitaxel-eluting polymer-based stent. METHODS: This is a first-in-man, single-center pilot trial that randomized 30 patients with 35 de novo coronary lesions in a 2:1 proportion to either the paclitaxel-eluting PicoElite stent (PES group: 20 patients with 24 lesions) or the bare metal ArthosPico stent (BMS group: 10 patients with 11 lesions). RESULTS: Baseline characteristics were similar in both groups, apart from younger patients in the PES group (mean age 63.5 years vs. 71.7 years in the BMS group; p = 0.032) and shorter lesion length in the PES group (9.56 mm vs. 14.25 mm in the BMS group; p = 0.02). In both groups, there was no difference in the primary endpoint of major adverse cardiac events (MACE) at 30-day follow up. There was a nonsignificant trend towards lower 6-month MACE and target lesion revascularization (TLR) rates in the PES group (10.5% PES vs. 40.0% in the BMS group for both; p = 0.143), and no stent thrombosis in the PES group. At 6-month angiographic follow up, the PES group demonstrated a significantly reduced in-stent binary restenosis rate (5.0% vs. 40.0%; p = 0.031), in-stent late loss (0.47 mm vs. 1.10 mm; p = 0.004), and in-segment late loss (0.72 mm vs. 1.16 mm; p = 0.016) as compared to the BMS group. CONCLUSIONS: The 6-month results of the APPLAUSE study demonstrate the safety and efficacy of the paclitaxel-eluting PicoElite stent for de novo lesions, with a significant reduction in late loss and a trend towards less TLR compared to a bare metal control.

Adult↗
PubMed2005

Two-year-plus follow-up of a paclitaxel-eluting stent in de novo coronary narrowings (TAXUS I).

Early results with polymer-based paclitaxel-eluting stents have shown significant improvements in the clinical and angiographic parameters of restenosis, as well as excellent safety outcomes. However, the duration of these beneficial effects is unknown. Therefore, the clinical outcomes of the TAXUS I study population were evaluated at 2- and 3-year follow-up. In TAXUS I, 61 patients with single, focal coronary lesions were randomly assigned to receive either a paclitaxel-eluting TAXUS stent (n = 31) or a bare metal control stent (n = 30). Low rates of composite major adverse cardiac events (MACEs) reported at 1-year follow-up (3.2% TAXUS vs 10.0% control) were maintained at 2 and 3 years, with no additional MACEs in either treatment group 1 year after implantation. The single target vessel revascularization in the TAXUS group was remote from the target lesion in contrast to 3 target lesion revascularizations in the control group.

Aged↗
PubMed2005

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents.

CONTEXT: Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. OBJECTIVE: To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. DESIGN, SETTING, AND PATIENTS: Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. INTERVENTIONS: Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. MAIN OUTCOME MEASURES: Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. RESULTS: At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR], 89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR, 6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR, 6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR, 3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR, 1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). CONCLUSIONS: The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.

Angioplasty, Balloon, Coronary↗
PubMed2005

Polymer-based paclitaxel-eluting stent for treatment of chronic total occlusions of native coronaries: results of a Taxus CTO registry.

The purpose of this prospective nonrandomized study was to evaluate both safety and efficacy of the polymer-based paclitaxel-eluting Taxus stent for treatment of chronic total coronary occlusions. Drug-eluting stents have been proven safe and efficacious in suppressing neointimal proliferation when used in simple native de novo coronary lesions. However, there are only limited data on safety and efficacy of these stents for treatment of more difficult lesion subsets, especially chronic total occlusions. Forty-five consecutive symptomatic patients with chronic total coronary occlusions were included in this observational single-arm study. Only patients with successfully crossed occlusions were enrolled. Primary endpoints were binary restenosis and late lumen loss at 6-month angiographic follow-up. Secondary endpoints were MACE at 30-day and 6-month follow-up. The 30-day MACE rate was 0%. At 6 months, the cumulative MACE-free survival was 84.4%. There were no deaths, myocardial infarctions, or stent thrombosis up to 6 months poststenting. At angiographic follow-up, the in-stent restenosis rate was 13.2% (5/38). There was a total of five in-stent restenoses, with three focal and two diffuse restenosis patterns. The in-segment late lumen loss was 0.13 +/- 0.58 mm. The stent edge analyses revealed a late loss of 0.21 +/- 0.66 proximally and a negative late loss of -0.10 +/- 0.67 at the distal edge segment. This study shows safety and indicators of efficacy of implantation of the paclitaxel-eluting Taxus stent for treatment of chronic total coronary occlusions. The quantitative angiographic analysis revealed beneficial results with respect to the efficacy surrogates binary restenosis rate and late loss.

Antineoplastic Agents, Phytogenic↗
PubMed2005

First report on a human percutaneous transluminal implantation of a self-expanding valve prosthesis for interventional treatment of aortic valve stenosis.

BACKGROUND: Percutaneous aortic valve replacement is a new technology for the treatment of patients with significant aortic valve stenosis. We present the first report on a human implantation of a self-expanding aortic valve prosthesis, which is composed of three bovine pericardial leaflets inserted within a self-expanding nitinol stent. The 73-year-old woman presented with severe symptomatic aortic valve stenosis (mean transvalvular gradient of 45 mmHg; valve area of 0.7 cm2). Surgical valve replacement had been declined for the patient because of comorbidities, including previous bypass surgery. METHOD AND RESULTS: A retrograde approach via the common iliac artery was used for valve deployment. The contralateral femoral vessels were used for a temporary extracorporal circulation, unloading the left ventricle during the actual stent expansion. Clinical, hemodynamic, and echocardiographic outcomes were assessed serially during the procedure. Clinical and echocardiographic follow-up at day 1, 2, and 14 post procedure was performed to evaluate the short-term outcome. The prosthesis was successfully deployed within the native aortic valve, with accurate and stable positioning and with no impairment of the coronary artery or vein graft blood flow. 2D and doppler echo immediately after device deployment showed a significant reduction in transaortic mean pressure gradient (from 45 to 8 mmHg) without evidence of aortic or mitral valve insufficiency. The clinical status has then significantly improved. These results remained unchanged up to the day 14 follow-up. CONCLUSION: This case report demonstrates a successful percutaneous implantation of a self-expanding aortic valve prosthesis with remarkable functional and clinical improvements in the acute and short-term outcome.

Aged↗
PubMed2004

Six- and twelve-month results from first human experience using everolimus-eluting stents with bioabsorbable polymer.

BACKGROUND: Everolimus, an active immunosuppressive and antiproliferative agent of the same family as sirolimus (rapamycin), has demonstrated significant reduction of neointimal proliferation in animal studies. The First Use To Underscore restenosis Reduction with Everolimus (FUTURE) I trial was the first in-human experience to evaluate the safety and efficacy of everolimus-eluting stents (EES), coated with a bioabsorbable polymer, compared with bare metal stents (BMS). METHODS AND RESULTS: FUTURE I was a prospective, single-blind, randomized trial that enrolled 42 patients with de novo coronary lesions (EES 27, BMS 15). Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low at 30 days and 6 months, without any early or late stent thrombosis for either group (P=NS). Between 6 and 12 months, there were no additional reports of major adverse cardiac events. The 6-month angiographic in-stent restenosis rate was 0% versus 9.1% (1 patient) (P=NS), with an associated late loss of 0.11 mm versus 0.85 mm (P<0.001), and the in-segment restenosis rate was 4% (1 patient) and 9.1% (1 patient) (P=NS) for EES and BMS, respectively. Intravascular ultrasound analysis revealed a significant reduction of percent neointimal volume in EES compared with BMS (2.9+/-1.9 mm3/mm versus 22.4+/-9.4 mm3/mm, P<0.001). There was no late stent malapposition in either group. The safety and efficacy of the EES appeared to be sustained at 12 months. CONCLUSIONS: In this initial clinical experience, EES with bioabsorbable polymer demonstrated a safe and efficacious method to reduce in-stent neointimal hyperplasia and restenosis.

Aged↗
PubMed2003

TAXUS I: six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions.

BACKGROUND: The TAXUS NIRx stent (Boston Scientific Corp) provides local delivery of paclitaxel via a slow-release polymer coating. The TAXUS I trial was the first in-human experience evaluating safety and feasibility of the TAXUS NIRx stent system compared with bare NIR stents (control) (Boston Scientific Corp) for treatment of coronary lesions. METHODS AND RESULTS METHODS AND RESULTS: The TAXUS I trial was a prospective, double-blind, three-center study randomizing 61 patients with de novo or restenotic lesions (< or =12 mm) to receive a TAXUS (n=31) versus control (n=30) stent (diameter 3.0 or 3.5 mm). Demographics, lesion characteristics, clinical outcomes were comparable between the groups. The 30-day major adverse cardiac event (MACE) rate was 0% in both groups (P=NS). No stent thromboses were reported at 1, 6, 9, or 12 months. At 12 months, the MACE rate was 3% (1 event) in the TAXUS group and 10% (4 events in 3 patients) in the control group (P=NS). Six-month angiographic restenosis rates were 0% for TAXUS versus 10% for control (P=NS) patients. There were significant improvements in minimal lumen diameter (2.60+/-0.49 versus 2.19+/-0.65 mm), diameter stenosis (13.56+/-11.77 versus 27.23+/-16.69), and late lumen loss (0.36+/-0.48 versus 0.71+/-0.48 mm) in the TAXUS group (all P<0.01). No evidence of edge restenosis was seen in either group. Intravascular ultrasound analysis showed significant improvements in normalized neointimal hyperplasia in the TAXUS (14.8 mm3) group compared with the control group (21.6 mm3) (P<0.05). CONCLUSIONS: In this feasibility trial, the TAXUS slow-release stent was well tolerated and showed promise for treatment of coronary lesions, with significant reductions in angiographic and intravascular ultrasound measures of restenosis.

Aged↗
PubMed2003

Initial multicenter experience with a novel distal protection filter during carotid artery stent implantation.

Atheroembolization resulting in transient or permanent neurologic impairment is the most common complication of catheter-based percutaneous carotid artery intervention. Protection of the distal cerebral vasculature during carotid stent implantation may enhance procedural safety. Carotid stent implantation with distal cerebral protection using the FilterWire EX was performed in 35 consecutive patients undergoing 36 procedures at six centers. The FilterWire was delivered and deployed successfully in all 36 cases, and embolic material was retrieved from 74% of procedures. The 30-day rate of major adverse events (death, major or minor stroke) was 0%. Transient ipsilateral periprocedural neurologic ischemia developed in two patients (5.7%), both resolving within 30 min. Distal cerebral protection with the FilterWire during carotid stenting is feasible and safe, results in capture and extraction of atheroembolic debris in the majority of patients while affording uninterrupted cerebral perfusion, and in this initial multicenter experience was associated with a high rate of procedural success without major complications.

Aged↗
PubMed2003

Optical Coherence Tomography (OCT). Potential of a new high-resolution intracoronary imaging technique.

BACKGROUND: It is believed that most myocardial infarctions result from the rupture of "vulnerable plaques", that share certain common characteristics. These plaques typically consist of a lipid-rich core in the central portion of the thickened intima, covered by a thin friable fibrous cap. Today, one of the important challenges in the field of interventional cardiology is how to identify minor or silent plaques that carry the risk of thrombosis resulting in severe cardiac events. Current imaging technologies lack the resolution to reliably identify these lesions. OCT: Optical Coherence Tomography (OCT) might have the potential to fill this role. OCT is a new non-contact, light-based imaging modality providing in situ images of tissues at near histologic resolution. As shown in various preclinical and clinical reports, OCT allows the identification of mural as well as luminal morphologies including lumen dimensions, plaques, thrombi, dissections, tissue flaps as well as information on stent geometries including apposition and symmetry. Trials comparing intravascular ultrasound (IVUS) and OCT demonstrated that OCT provided additional morphologic information, which could be used to improve plaque characterization. CONCLUSION: OCT has the potential to provide a new and more detailed look into the vessel wall, which might help to identify plaques that are at risk of rupture, and furthermore, which will influence and guide the appropriate patient-specific therapeutic approach.

Coronary Artery Disease↗
PubMed2002

Evaluation of a balloon occlusion and aspiration system for protection from distal embolization during stenting in saphenous vein grafts.

Distal embolization after angioplasty in degenerated saphenous vein grafts (SVGs) results in high rates of periprocedural myonecrosis and mortality. Temporary protection of the distal microcirculation with aspiration of dislodged debris may improve the safety of SVG intervention. To evaluate the feasibility, safety, and efficacy of distal protection using the PercuSurge GuardWire Occlusion and Aspiration System, 103 consecutive patients undergoing planned stenting of 105 SVG lesions were prospectively enrolled in a multinational, multicenter study. Before angioplasty, protection of the distal circulation was achieved with the PercuSurge GuardWire distal balloon occlusion system, followed by stenting and debris aspiration. Quality assurance measures in the study included independent on-site data monitoring, clinical event adjudication, data analysis, and use of multiple core laboratories. Mean graft age was 8.9 +/- 4.0 years. The duration of distal balloon inflation was 5.4 +/- 3.7 minutes; premature balloon deflation for ischemia was not required in any patient. Macroscopically visible red and/or yellow debris was extracted in 91% of patients. By core lab analysis, postprocedural Thrombolysis In Myocardial Infarction-III flow was present in 98.9% of grafts (vs 83.5% before intervention). No patient developed angiographic evidence of no reflow or distal embolization. Postprocedural creatine phosphokinase MB isozyme levels were elevated to >3 x normal in only 5 patients (5%), and 97 patients (94%) were free of major adverse events at 30 days. We conclude that the GuardWire distal balloon occlusion and aspiration system is an effective and safe method for protecting distal microcirculation from the adverse consequences of embolization during mechanical intervention of degenerated SVGs.

Aged↗
PubMed2002

[State of treatment of coronary artery disease by drug releasing stents].

BACKGROUND: Despite improved technologies restenosis remains the main drawback of catheter-based interventions in coronary artery disease. Local application of anti-proliferative drugs through drug releasing stents is a promising concept addressed to solve this problem. DRUG RELEASING STENTS: Today, given the technical capabilities for controlled drug release from coronary stents, the development of drug eluting stents has emerged as one of the main research areas in interventional cardiovascular medicine. Several different approaches for drug loading on coronary stents as well as a variety of antiproliferative and anti-inflammatory agents, such as paclitaxel, actinomycin D, sirolimus, tacrolimus, everolimus and dexamethasone are under clinical investigation. RESULTS: Since the first enthusiastic reports from first in-man observations with drug coated stents, the success of the combination of both a biological and a mechanical approach has been proved in several controlled studies with restenosis rates between 0% in the RAVEL trial (sirolimus, Cordis Bx Velocity trade mark stent), 0% in the TAXUS I trial (paclitaxel, Boston Scientific NIRx trade mark stent) and 4% in the ASPECT Study (paclitaxel, Cook V-Flex plus trade mark stent). The risk of stent thrombosis seems to depend on the dose of the antiproliferative drug - in the SCORE trial stent thrombosis occurred in 6.3% of patients with high dose of QP2 and the antiplatelet therapy, in the ASPECT subgroup with cilostazol instead of clopidogrel and high dose of paclitaxel in up to 25%, whereas in RAVEL and TAXUS I no stent thrombosis was observed. CONCLUSION: If the "one digit" restenosis rate observed in clinical trials could be confirmed in clinical practice without increase of complications, especially stent thrombosis using multiple and/or long stents, we can expect in the near future that implanting drug eluting stents in larger patient groups and lesion subsets will cause a reduction of patients with need for surgical revascularization.

Angioplasty, Balloon, Coronary↗