A novel drug-coated scoring balloon for the treatment of coronary in-stent restenosis: Results from the multi-center randomized controlled PATENT-C first in human trial

ACKGROUND:Scoring balloons produce excellent acute results in the treatment of in-stent restenosis (ISR), fibro-calcific and bifurcation lesions but have not been shown to affect the restenosis rate. A novel paclitaxel-coated scoring balloon (SB) was developed and tested to overcome this limitation.METHODS AND RESULTS:SB were coated with paclitaxel admixed with a specific excipient. Patients at four clinical sites in Germany and one in Brazil with ISR of coronary bare metal stent (BMS) were randomized 1:1 to treatment with either a drug-coated or uncoated SB. Baseline and 6-month follow-up quantitative coronary angiography was performed by an independent blinded core lab and all patients will be evaluated clinically for up to one year. The primary endpoint was angiographic in-segment late lumen loss (LLL). Secondary endpoints included the rate of clinically driven target lesion revascularization (TLR), composite of major adverse cardiovascular events (MACE), stent thrombosis and other variables. Sixty-one patients were randomized (28 uncoated and 33 drug-coated SB); mean age 65 years, males 72%, and presence of diabetes 39%. At 6-month angiography, in-segment LLL was 0.48 ± 0.51 mm in the uncoated SB group versus 0.17 ± 0.40 mm in the drug-coated SB group (P = 0.01; ITT analysis). The rate of binary restenosis was 41% in the uncoated SB group versus 7% in the drug-coated SB group (P = 0.004). The MACE rate was 32% with the uncoated SB vs. 6% in the drug-coated SB group (P = 0.016). This difference was primarily due to the reduced need for clinically driven TLR in the coated SB group (3% vs. 32% P = 0.004)...

Impact of the Duett sealing device on quality of life and hospitalization costs for coronary diagnostic and interventional procedures: Results from the Study of Economic and Quality of Life substudy of the SEAL trial.

BACKGROUND: The Simple and Effective Arterial Closure (SEAL) trial examined the safety and effectiveness of the Duett vascular sealing device (Vascular Solutions, Minneapolis, Minn) versus manual compression after diagnostic and interventional coronary procedures. We compared quality of life and initial hospitalization costs among patients treated with the Duett device versus manual compression. METHODS: Functional status was assessed with the Duke Activity Status Index (DASI) at 7 and 30 days after intervention. General health status was assessed with the Short Form (SF-36) at 30 days after intervention. Hospitalization costs were derived from the UB92 formulation of the hospital bill. RESULTS: There was a strong trend toward higher functional status in patients receiving treatment with the Duett device at 7 days both before (P =.04) and after (P =.08) adjustment for significant covariates. This difference was significant in the diagnostic group but not in the interventional group. No significant differences in quality of life between the Duett device and manual compression at 30 days were found. There was no significant difference in total hospitalization costs between treatment arms (P =.91). For interventional patients, mean total in-hospital costs were $10,167 in the Duett group and $10,225 in the manual compression group (P =.82). For diagnostic patients, mean hospitalization costs were $7784 and $7996 for the Duett device and manual compression groups, respectively (P =.72). Trends toward reduced recovery/observation room costs with the Duett device (P =.06) were found; this difference was significant in the diagnostic group ($198 vs $279, P =.02). CONCLUSIONS: The Duett sealing device was associated with significantly higher functional status at 7 days after the procedure in addition to shortened time to hemostasis and ambulation, with no associated increase in cost.

Arterial access site closure with a novel sealing device: Duett.

Management of arterial access sites following percutaneous endovascular procedures is associated with patient discomfort and local complications. A new vascular sealing device, comprised of a balloon delivery catheter and a flowable procoagulant consisting of thrombin and collagen, was tested. Immediately following catheterization 200 patients (age, 66.1 +/- 11.2 years) were treated with the sealing device (Duett). Of these 200 patients, 132 underwent diagnostic catheterization, 67 underwent percutaneous transluminal coronary angioplasty, and one underwent percutaneous transluminal angioplasty. The sheath sizes included 2-5 Fr, 166-6 Fr, 25-7 Fr and 7-8 Fr. All patients undergoing diagnostic procedures received at least 5,000 U of intravenous heparin during the procedure. The Duett was used successfully in 198/200 (99%) patients immediately following completion of the endovascular procedure. In two patients a device malfunction resulted in uncomplicated crossover to manual compression. The time to hemostasis ranged from 3 to 5 minutes. All patients were walking 2 to 5 hours following the procedure unless a complication had occurred. No patient experienced leg ischemia, required surgical repair of the arterial access site, or had an infection at the site. In three patients (1.5%), a pseudoaneurysm occurred and was successfully treated with ultrasound-guided compression and three patients received a blood transfusion. No late complications were observed following hospital discharge. This novel vascular sealing device successfully achieves rapid hemostasis and allows early ambulation following percutaneous endovascular procedures with a low incidence of complications.

Immediate sealing of arterial puncture sites after cardiac catheterization and coronary interventions: initial U.S. feasibility trial using the Duett vascular closure device.

The aim of this first U.S. feasibility study was to investigate the safety and efficacy of a novel vascular sealing device, Duett, following percutaneous endovascular procedures. Immediately following a catheterization procedure, the sealing device was deployed at the femoral arterial access site in 43 patients (diagnostic 29, intervention 11, intervention + abciximab 3). Patients were followed up at 1 month with clinical assessment, ankle-brachial index measurement, and Doppler ultrasound of the treated femoral artery puncture site. Successful hemostasis was achieved with the Duett alone in 42/43 (97.7%) patients. There was one uncomplicated crossover to manual compression. The time to hemostasis was 4.0+/-1.5, 6.9+/-4.2, and 5.8+/-1.2 min for diagnostic, interventional, and abciximab patients, respectively. At 1-month follow-up, one patient (2.3%) required ultrasound-guided compression for treatment of a pseudoaneurysm. There were no other major complications. This novel vascular sealing device appears to achieve rapid and safe hemostasis successfully immediately following a wide range of percutaneous endovascular procedures.

A novel vascular sealing device for closure of percutaneous arterial access sites.

The purpose of this study was to investigate the safety and efficacy of a novel vascular sealing device that incorporates a unique low-profile balloon-positioning catheter and a procoagulant delivered after diagnostic cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA) procedures. Current management of the vascular access site after percutaneous interventions is associated with patient discomfort and complications. Based on previously reported successful results in canine models, we proceeded with this first human feasibility and safety study. Immediately after an invasive procedure, the sealing device was successfully deployed at the femoral arterial access site in 24 of 24 procedures (diagnostic 19, PTCA 5). All patients were followed up at 1 month with clinical assessment, ankle-brachial index measurement, and Doppler ultrasound. Successful hemostasis was achieved in all patients. The activated clotting time before sealing device deployment was 125.5 +/- 22.2 and 267.8 +/- 60.0 seconds for diagnostic and PTCA patients, respectively. The time to hemostasis was 2.5 +/- 0.9 minutes for diagnostic and 6.0 +/- 2.2 minutes for PTCA patients. No major complications were observed. Coagulation markers (fibrinogen, D-dimer, thrombin-antithrombin-3 complex, and prothrombin fragment 1 and 2) measured before and after sealing device deployment did not reveal excessive intravascular thrombin generation or other coagulopathy. This novel vascular sealing device successfully achieves safe and effective vascular access site hemostasis immediately after cardiac catheterization and PTCA. These promising first human results will need to be confirmed by a multicenter randomized trial.

The Duett closure device: concept and experimental results.

Purpose of this paper is to investigate the hemostatic capabilities of a novel vascular sealing device consisting of a balloon catheter and procoagulant. Vascular sheaths were placed percutaneously in the femoral arteries of dogs. The sealing device was evaluated using the balloon catheter alone in 6 femoral arteries and with the addition of a procoagulant in 21 femoral arteries. The balloon catheter alone was successfully deployed in 6 of 6 femoral arteries achieving immediate hemostasis. In a second study in which the procoagulant was delivered following balloon placement, the sealing device was successfully deployed and hemostasis was achieved in 20 of 21 attempts (95%) despite removal of the balloon catheter. In a subset of fully anticoagulated animals, hemostasis was achieved in the sealing device-treated arteries at 6.5 +/- 3.4 minutes but in none of the controls (p < 0.001). This novel vascular sealing device successfully achieves rapid hemostasis in normal and anticoagulated dogs following percutaneous vascular procedures.

Final report of the European multi-center registry using the Duett vascular sealing device.

Duett, a novel vascular sealing device, was first clinically used in July 1997. A European multi-center registry was established to evaluate the safety and procedural success of the Duett sealing device in a broad range of patients undergoing diagnostic or interventional endovascular procedures. At 25 European sites 1587 patients were enrolled. All patients (> or = 18 years) must have given informed consent for the use of the sealing device after a diagnostic and/or interventional endovascular procedure performed via a femoral arterial approach. Standard length (< or = 10 cm) 5 to 9 F introducer sheaths had to be used. An ACT of < or = 400 s, and any approved GP IIb/IIIa platelet receptor antagonist was permitted. Successful deployment could be achieved in 96.2% (1526/1587 patients) with complete hemostasis within 2 to 5 minutes in over 95% of the patients. The complication-free rate was 96.4%. Arterial occlusions were rare (4 patients) and successfully treated with surgical repair in 1 and with thrombolysis in 3 patients. Pseudoaneurysms occurred in 34 patients, the majority (30/34) were successfully treated with ultrasound-guided compression or resolved spontaneously. The total rate of major complications was 2.6% (41/1587). The final results of the European registry demonstrate that the Duett sealing device can be used with a high procedural success following diagnostic and interventional endovascular procedures. The incidence of major complications is low and comparable to all other approved vascular closure devices and manual compression. CE-mark certification was approved at the end of 1998.

Novel vascular sealing device for closure of percutaneous vascular access sites.

To investigate the hemostatic capabilities of a novel vascular sealing device consisting of a balloon catheter and procoagulant, vascular sheaths were placed percutaneously in the femoral arteries of dogs. The sealing device was evaluated using the balloon catheter alone in six femoral arteries and with the addition of a procoagulant, in 21 femoral arteries. The balloon catheter alone was successfully deployed in six of six femoral arteries achieving immediate hemostasis. In a second study in which the procoagulant was delivered following balloon placement, the sealing device was successfully deployed and hemostasis was achieved in 20 of 21 attempts (95%) despite removal of the balloon catheter. In a subset of fully anticoagulated animals, hemostasis was achieved in the sealing device-treated arteries at 6.5+/-3.4 minutes, but in none of the controls (P < 0.001). This novel vascular sealing device successfully achieves rapid hemostasis in normal and anticoagulated dogs following percutaneous vascular procedures.

Regression of severe atherosclerotic plaque in patients with mild elevation of LDL cholesterol.

BACKGROUND: Intensive risk factor reduction in patients with dyslipidemias and coronary atherosclerosis has been shown to result in alterations in coronary artery morphology and reduced clinical events. However, the impact of such interventions in populations with relatively normal levels of low-density lipoproteins (LDL) is unclear. METHODS: To test the hypothesis that intensive risk factor reduction results in angiographic regression in patients with only mildly elevated levels of LDL, 14 patients with angiographically proven coronary atherosclerosis were entered into the University of California Davis Coronary Artery Disease Regression Program and intensively treated with pharmacologic and nonpharmacologic interventions for 2 years. Quantitative angiography was performed prior to and after 2 years of therapy to determine changes in coronary artery diameter. RESULTS: As a result of this program, dietary fat intake was reduced by 58% and LDL fell from 120 +/- 7 mg/dL to 104 +/- 6 mg/dL (p = 0.05). The average diameter of the measured arterial locations (including all 53 stenoses and 292 nondiscrete regions) on study entry was 2.74 +/- 0.05 mm. After 24 months, there was a net increase in arterial diameter (regression) of +0.05 +/- 0.04 mm to 2.81 +/- 0.05 mm (p = 0.01). While there was no significant change in the average diameter of discrete stenoses, all 8 lesions > or = 50% initial diameter narrowing regressed, with a mean diameter change of + 0.2 mm. Conversely, only 1 of 8 mild lesions < or = 20% regressed, while 4 progressed. Intermediate lesions (20% to 50%, n = 37) had balanced progression and regression. CONCLUSIONS: When examined as a continuous variable, there was a significant linear correlation between initial lesion severity (% stenosis) and the extent of regression (mm). Therefore, risk factor reduction (dietary therapy, exercise, psycho-social counseling, and lipid lowering therapy) in patients with only mild dyslipidemia results in angiographic regression of more severe lesions (> 50% initial stenosis), but does not prevent progression of mild lesions (< 20%). These findings demonstrate that intensive risk factor reduction in patients with only mild elevation of lipids beneficially influences the morphology of the most severe lesions.

Coronary angioplasty of branch vessels associated with an extreme angle take-off.

Stenoses in branch vessels which originate at acute angle to the main vessel represent a technically challenging anatomy for the performance of balloon angioplasty [PTCA]. We report a novel technique utilizing a distally placed perfusion balloon that facilitated guidewire placement and subsequent balloon angioplasty of a branch vessel stenosis.

Intracoronary Doppler flow to monitor the results of selective saphenous vein graft thrombolytic therapy.

Selective intracoronary thrombolytic therapy has recently been advocated as a technique to recanalize occluded coronary bypass grafts. We report a novel approach for monitoring the results of this treatment utilizing a coronary artery doppler flow guidewire. This approach may optimize the duration of thrombolytic treatment in these patients.

Balloon catheter retrieval of dislodged coronary artery stents: a novel technique.

Potential complications of intracoronary stenting include stent dislodgement and embolization. We describe a patient in whom a stent was dislodged from a coronary balloon catheter to the iliac artery. A peripheral angioplasty balloon was used to withdraw the stent into the arterial sheath and thereby remove it from the patient.

Reversible coronary artery kinking caused by cardiopulmonary support.

Cardiopulmonary support is utilized to provide optimal hemodynamic stability in high risk patients undergoing percutaneous transluminal coronary angioplasty. This report describes a patient undergoing supported angioplasty in whom multiple new severe stenoses were noted following coronary dilation and that were completely reversed by discontinuing cardiopulmonary support.

Coronary thrombus: a novel catheter-based approach to treatment.

The presence of coronary thrombus during intracoronary interventions increases the risk of complications during the procedure. We describe a novel approach to infusing thrombolytic agents selectively into a coronary artery utilizing a new low-profile perfusion balloon. This approach may add a useful new treatment for resistant intracoronary thrombi.

Percutaneous transluminal coronary angioplasty of chronic total occlusions. Primary success, restenosis, and long-term clinical follow-up.

BACKGROUND: Angioplasty of chronically totally occluded vessels has been associated with a success rate well below and restenosis rate well above that for angioplasty of stenosed segments. However, long-term clinical outcome after successful revascularization of a chronically totally occluded vessel has not been reported in detail. METHODS AND RESULTS: Accordingly, data for 480 patients undergoing angioplasty for chronic total occlusion at Emory University Hospital, Atlanta, Ga., from 1980 to 1988 were analyzed for predictors of in-hospital procedural and clinical (procedural success and absence of in-hospital complications) success, restenosis, and 4-year clinical follow-up. The study population was grouped by procedural and clinical success and failure. The groups were then compared for outcome, both in hospital and long term. The initial clinical success rate was 66% (317 of 480 patients). Independent correlates of failure were the number of vessels diseased (p less than 0.001), vessel location of the lesion (p = 0.016), and absence of any distal antegrade filling (p = 0.002). Follow-up data revealed 98% cardiac survival and 96% overall survival at 4 years for the group as a whole. Freedom from myocardial infarction or cardiac death was significantly greater in patients with clinical success (93%) than with clinical failure (89%, p = 0.0044). In the successful group, 87% were free from coronary surgery after 4 years compared with 64% in the failure group (p less than 0.0001). Two thirds of the patients were free of angina at last follow-up. The presence of angina at follow-up was the same for patients successfully treated and for those with failed angioplasty, which may be related to the frequent use of coronary surgery in the failure group. CONCLUSIONS: In well-selected cases, the success rate for angioplasty of chronic total occlusion is acceptable. Furthermore, long-term clinical benefit is suggested by the high freedom from coronary surgery, myocardial infarction, and death in the patients who underwent successful revascularization.

Correction of subclavian artery stenosis by percutaneous angioplasty.

Subclavian artery stenosis is an infrequently recognized cause of left-sided chest and arm pain that can mimic the signs and symptoms of angina pectoris. In addition, more proximal subclavian artery stenoses can be associated with cerebrovascular symptoms in the "subclavian steal syndrome." This article reviews the clinical experience in four patients who presented with different manifestations of subclavian artery stenosis and who were all successfully treated by percutaneous angioplasty. Their clinical presentation, angiographic findings, and post-angioplasty results are documented. In conclusion, it is felt that nonsurgical correction of critical subclavian artery stenosis, using current angioplasty techniques, is the preferred method of treatment.

Risk factors, time course and treatment effect for restenosis after successful percutaneous transluminal coronary angioplasty of chronic total occlusion.

Advances in technology and operator experience, and increased use of angiography early after myocardial infarction have led to greater use of percutaneous transluminal coronary angioplasty (PTCA) for chronic, total coronary artery occlusions. To better assess long-term outcome, 257 consecutive patients with successful PTCA of a total occlusion with late angiographic follow-up from 484 patients (53%) with PTCA success were reviewed. The mean +/- standard deviation patient age was 54 +/- 10 years, 79% were men, the duration of total occlusion was 11 +/- 15 weeks and the post-PTCA diameter stenosis was 24 +/- 12%. Eighty-two, 27 and 63% of patients received long-term aspirin, dipyridamole and warfarin therapy, respectively. Angiography at 8 +/- 8 months demonstrated restenosis (greater than or equal to 50% diameter stenosis) in 41% of patients restudied within 6 months and in 66% of patients restudied within 12 months by life table analysis. In multivariate regression analysis of 19 variables, 2 were independently correlated with the occurrence of restenosis: post-PTCA diameter stenosis greater than 30% (p = 0.02) and coronary artery dilated (left anterior descending and right coronary arteries greater than the left circumflex coronary artery) (p = 0.05). In log rank analysis that also considered the timing of angiographic detection of restenosis, dilatation of a proximal left anterior descending stenosis was also a significant predictor of restenosis (p = 0.01), and dilatation within 4 weeks of the presumed time of occlusion was only weakly predictive (p = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)