Gregory A. Braden

Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study☆

Background—The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. Methods and Results—Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACEs: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve ≥95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P =0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those ≥70% inhibited (P =0.009). By multivariate analysis, platelet function inhibition ≥95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P =0.04). Conclusions—Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.

Endothelial-dependent coronary vasomotor responsiveness in postmenopausal women with and without estrogen replacement therapy.

Recently, Williams et al’ reported that acute administration of estrogen attenuates the coronary vasoconstrictor response to acetylcholine in atherosclerotic cynomolgus monkeys. These observations suggest that estrogen plays a fundamentally important role in the relationship between coronary vascular endothelium and vascular smooth muscle. This study examines the influence of current estrogen replacement therapy in postmenopausal women on endothelial-dependent and independent vasomotor responsiveness to acetylcholine. Ten postmenopausal women with exertional angina undergoing routine diagnostic coronary angiography or percutaneous transluminal coronary angioplasty were studied. The protocol was approved by the Clinical Research Practices Committee and each subject gave informed consent before the study, Four women were taking estrogen replacement therapy (PremarinB 0.625 to 1.25 mglday or topical estradiol 0.1 mg). None of the women were taking progesterone. All of the women had minimal coronary artery narrowings in the proximal portion of the left anterior descending or a nondominant circumflex coronary artery. Vasoactive medications were withheld for 12-24 hours before the procedure. A 3Fr infusion catheter was positioned in the proximal left anterior descending or proximal circumflex artery through the guiding catheter. After the baseline angiogram was recorded, 3 consecutive 2-minute infusions of acetylcholine were administered into the proximal coronary artery. The

Vascular closure devices in patients treated with anticoagulation and IIb/IIIa receptor inhibitors during percutaneous revascularization.

ow rate (0.8 mllmin) was calculated to deliver a final estimated blood concentration of 10s, 10m7 and 10m6 M. After each acetylcholine infusion, repeat angiography was performed in an identical fashion to baseline. After the third acetylcholine in& sion and angiogram, a 50 pg bolus of nitroglycerin was administered and a final coronary angiogram was recorded. Heart rate, blood pressure and appropriate electrocardiographic leads were monitored during the infusions to verify the absence of any changes in hemodynamic status or evidence of &hernia. Proximal and midvessel segments of the coronary artery distal to the tip of the infusion catheter were analyzed without knowledge of the estrogen status using a quantitative coronary angiography method (Gammasonits, Chicago, Illinois). When possible, coronary segments from the noninfused half of the left coronary distribution

Qualitative and quantitative contrasts in the mechanisms of lumen enlargement by coronary balloon angioplasty and directional coronary atherectomy

OBJECTIVES The study assessed clinical outcomes of closure device use following percutaneous coronary revascularization using current standards of anticoagulation and antiplatelet therapy. BACKGROUND Evaluation of the outcomes of patients by use of vascular closure devices during coronary interventions employing current standards of anticoagulation and glycoprotein (GP) IIb/IIIa inhibitor therapy is limited. METHODS We evaluated outcomes of 4,525 consecutive patients who underwent percutaneous coronary intervention between July 1997 and April 2000. All patients received anticoagulation with heparin and GP IIb/IIIa inhibitor therapy with abciximab. The closure method was manual in 1,824 patients, Angioseal in 524 patients and Perclose in 2,177 patients. Procedural and hospital vascular outcomes were evaluated. RESULTS Closure device success was 97.1% Angioseal and 94.1% Perclose (p < 0.05). Minor vascular complications occurred in 1.8% of manual patients, 1.1% of Angioseal patients and 1.2% of Perclose patients (p = NS); major complications occurred in 1.3% of manual patients, 1.1% of Angioseal patients and 1.0% of Perclose patients (p = NS). Multivariate logistic regression identified only closure device failure as an independent predictor of a vascular complication. In patients with successful closure with a device, minor complications (0.8% vs. 1.8%, p < 0.05) and any complication (1.5% vs. 2.5%, p < 0.05) were reduced compared to manual compression. CONCLUSIONS Arterial closure following coronary interventions using anticoagulation and GP IIb/IIIa inhibitor therapy can be safely and effectively performed, with vascular complication rates similar to or lower than with manual pressure. Additionally, vascular complication rates using GP IIb/IIIa inhibitor therapy regardless of the method of arterial closure are equivalent to or lower than previously published rates of vascular complications.

Assessment of Coronary Arterial Restenosis With Phase-Contrast Magnetic Resonance Imaging Measurements of Coronary Flow Reserve

OBJECTIVES This study was designed to define and contrast the mechanisms of lumen enlargement from coronary balloon angioplasty and directional coronary atherectomy using intracoronary ultrasound imaging in vivo. BACKGROUND The mechanisms of lumen enlargement produced by percutaneous transluminal coronary balloon angioplasty and directional coronary atherectomy are not known because the coronary artery wall has not previously been studied both before and after dilation. METHODS We used intracoronary ultrasound to quantitate coronary lumen, vessel and plaque area both before and immediately after successful coronary angioplasty (n = 30) and directional coronary atherectomy (n = 25) at the site of most severe stenosis. RESULTS Angioplasty increased lumen area by 2.80 +/- 0.25 mm2 (mean +/- SE, p < 0.0001). Eighty-one percent of this lumen gain resulted from an increase in vessel area and the remaining 19% from a reduction in plaque area. Lumen gain of individual lesions was separated into three groups: 67% had an increase in vessel area (vessel expansion), 13% had a decrease in plaque area and 20% had a combination of both. In contrast, vessel expansion contributed only 22% of the lumen gain with directional coronary atherectomy, with the majority (78%) of increase in lumen size coming from a reduction in plaque area. Directional coronary atherectomy increased lumen area from 2.36 +/- 0.05 to 7.00 +/- 0.28 mm2 (p < 0.0001). Plaque reduction was the sole mechanism in 60% of lesions, vessel expansion was the sole mechanism in 12% and a combination of both mechanisms occurred in 28%. Lumen enlargement of eccentric lesions treated with directional coronary atherectomy was more commonly associated with plaque reduction (p < 0.02), whereas eccentricity did not affect the mechanism of lumen enlargement with coronary angioplasty. CONCLUSIONS This is the first study to systematically examine the coronary artery wall in vivo at the site of a severe stenosis both before and after catheter-based interventions in humans. Lumen enlargement from coronary angioplasty occurs predominantly from vessel expansion or stretching, although a reduction in plaque area contributes to the lumen gain in many patients and is the sole mechanism in a few. Lumen gain from directional coronary atherectomy is predominantly from reduction in plaque area (probably owing to tissue removal), although vessel stretching (balloon effect) occurs and is the sole mechanism in a small minority of vessels. Plaque reduction is more common in directional coronary atherectomy of eccentric lesions.

Vitaxin, a Humanized Monoclonal Antibody to the Vitronectin Receptor (αvβ3), Reduces Neointimal Hyperplasia and Total Vessel Area After Balloon Injury in Hypercholesterolemic Rabbits

BACKGROUND After successful percutaneous coronary arterial revascularization, 25% to 60% of subjects have restenosis, a recurrent coronary arterial narrowing at the site of the intervention. At present, restenosis is usually detected invasively with contrast coronary angiography. This study was performed to determine if phase-contrast MRI (PC-MRI) could be used to detect restenosis noninvasively in patients with recurrent chest pain after percutaneous revascularization. METHODS AND RESULTS Seventeen patients (15 men, 2 women, age 36 to 77 years) with recurrent chest pain >3 months after successful percutaneous intervention underwent PC-MRI measurements of coronary artery flow reserve followed by assessments of stenosis severity with computer-assisted quantitative coronary angiography. The intervention was performed in the left anterior descending coronary artery in 15 patients, one of its diagonal branches in 2 patients, and the right coronary artery in 1 patient. A PC-MRI coronary flow reserve value </=2.0 was 100% and 82% sensitive and 89% and 100% specific for detecting a luminal diameter narrowing of >/=70% and >/=50%, respectively. CONCLUSIONS Assessments of coronary flow reserve with PC-MRI can be used to identify flow-limiting stenoses (luminal diameter narrowings >70%) in patients with recurrent chest pain in the months after a successful percutaneous intervention.

A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention: Results of the Evaluating Enoxaparin Clotting Times (ELECT) Study

The vitronectin receptor (alphavbeta3) mediates several biological processes that are critical to the formation of a neointima after coronary interventions. Blockade of alphavbeta3 could reduce neointima formation by inhibiting smooth muscle cell migration, decreasing transforming growth factor-beta1 expression, enhancing apoptosis, or reducing neovasculature. The effects of short-term administration of Vitaxin, a humanized monoclonal antibody to alphavbeta3, on the responses to balloon injury were tested in hyperlipidemic rabbits. Balloon angioplasty was performed on the iliac arteries of male New Zealand White rabbits that were fed an atherogenic diet for 1 week before injury and until euthanization at 4 weeks. Rabbits were given either saline (control) or 1 of 2 dosing regimens of Vitaxin (high dose, 5.0 mg/kg, and low dose, 0.5 mg/kg), which were administered intra-arterially before injury and intramuscularly on days 2 and 3. High-dose and low-dose Vitaxin were equally effective in decreasing neointima formation even in the presence of hypercholesterolemia, a stimulus to alphavbeta3 expression. Vitaxin reduced transforming growth factor-beta1 and enhanced apoptosis in injured arteries. Despite these positive effects, Vitaxin administration was associated with a reduction in artery size, indicating a negative effect on remodeling. Vitaxin has a potential role in preventing intimal hyperplasia, especially if the negative effects on remodeling can be overcome, by dose adjustment or other strategies.

Rotational atherectomy or balloon angioplasty in the treatment of intra-stent restenosis: BARASTER Multicenter Registry†

OBJECTIVES The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every approximately 30-s rise. CONCLUSIONS Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal.

Successful “pre-closure” of 7Fr and 8Fr femoral arteriotomies with a 6Fr suture-based device (the Multicenter Interventional Closer Registry)

The BARASTER registry was formed to evaluate the initial success and long‐term results of rotational atherectomy in the management of in‐stent restenosis. Rotational atherectomy was used in 197 cases of in‐stent restenosis: 46 with stand‐alone rotational atherectomy or at most 1 atmosphere of balloon inflation (Rota strategy), and 151 with rotational atherectomy and adjunctive balloon angioplasty <1 atmosphere (Combination strategy). These were compared with 107 episodes of in‐stent restenosis treated with balloon angioplasty alone. In this observational study, the use of Combination therapy was associated with a slightly higher initial success rate (95% vs. 87% with the Rota strategy and 89% with Balloons, P = 0.08). There was a reduction in one year clinical outcomes (death, myocardial infarction or target lesion revascularization) in the combination group (38% vs. 60% with Rota and 52% with balloons, P = 0.02). These data support a benefit of the strategy of debulking with rotational atherectomy followed by adjunctive balloon angioplasty, in the management of in‐stent restenosis. Cathet. Cardiovasc. Intervent. 51:407–413, 2000.

Transluminal Extraction Catheter Atherectomy Followed by Immediate Stenting in Treatment of Saphenous Vein Grafts

The arterial sheath remains a cause of vascular complications, restricted mobility, and discomfort in patients who have undergone percutaneous interventional procedures. The rate of vascular complications and bleeding increases with longer sheath dwell times. Larger sheath sizes further elevate this risk, as might the administration of antithrombotic agents and intravenous glycoprotein IIb/IIIa inhibitors. Arterial closure devices have been advocated as a means of increasing patient comfort and facilitating rapid ambulation after interventional procedures, while possibly decreasing complication rates. Arterial closure with the 8Fr or 10Fr suture-based Prostar-Plus (Perclose Inc., Redwood City, California) has previously been shown to provide effective hemostasis. Use of the 6Fr suture-based Techstar has been shown to be effective for closure of 6Fr sheaths, but use of the smaller 6Fr device for 7Fr and 8Fr holes has not been systematically examined. Although the 8Fr device can provide hemostasis for 8Fr sheaths effectively, the current version requires subcutaneous dissection with formation of a soft tissue tract from the skin to the level of the artery. Such a tract can lead to continuous oozing, particularly in the presence of glycoprotein IIb/IIIa blockade. Potentially, such a tract may also increase the risk of infection. Therefore, use of a smaller device to close the hole formed by a larger sheath, without the need for tract formation, could represent an advance in suture-based arterial closure. The goal of this study was to determine if such an approach is safe and effective. • • • The Closer trial is a prospective registry of 380 patients conducted at 10 centers in the United States from March 2000 to December 2000. Of these, 160 patients undergoing coronary or peripheral intervention through 7Fr to 8 Fr sheaths had percutaneous sutures deployed before sheath placement (“preclose” arm), with tying of sutures after sheath removal. The preclose arm of the Closer trial was prespecified and independently powered for analysis. Informed consent was obtained from all patients. The technique of preclosure involves initial placement of a smaller size sheath than the size intended for the procedure (Figure 1). Specifically, a 6Fr sheath was placed initially. An angiogram of the femoral artery was performed to ensure placement of the sheath above the bifurcation of the superficial femoral artery and the profunda femoris branch. A femoral artery diameter of at least 5 mm and absence of any significant atheroma at the puncture site were required. If these conditions were met, then the sheath was exchanged over a guidewire for the 6Fr Closer device. The device was positioned in the artery, the sutures deployed, and the device removed over the wire, with placement of the 7Fr or 8Fr sheath. The interventional procedure was performed and once completed, the sheath was removed and the sutures tied, obtaining hemostasis. If the operator elected to maintain arterial access during this last step, the wire was reintroduced as the knot was tightened, with the wire removed just before the knot was cinched. The prespecified historical control consisted of interventional patients randomized to manual compression from the Suture To Ambulate aNd Discharge (STAND II) trial. The primary safety end point was the incidence of 30-day major groin complications, whereas the primary efficacy end point was time to discharge, measured from the time of sheath removal to the time the patient left the hospital. Secondary end points included time to hemostasis and ambulation, as well as device and procedural success. Differences in means were calculated with 95% confidence intervals. Tests of significance were performed using the nonparametric Wilcoxon method. Statistical calculations were performed with Intercooled Stata 6.0 (Stata Corp., College Station, Texas) and Microsoft Excel 5.0 (Microsoft Corp., Redmond, Washington). The mean activated clotting time was 232 seconds in the Closer patients. There were no significant differences in baseline characteristics, other than more From the Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland Ohio; Evanston Hospital, Evanston, Illinois; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Arkansas Heart Hospital, Little Rock, Arkansas; Arizona Heart Institute, Phoenix, Arizona; Sacred Heart Hospital, Pensacola, Florida; Fountain Valley Regional Hospital, Fountain Valley, California; and the St. Joseph’s Hospital, Atlanta, Georgia. Dr. Bhatt’s address is: Cleveland Clinic Foundation, Department of Cardiovascular Medicine/Desk F25, 9500 Euclid Avenue, Cleveland, Ohio 44195. E-mail: bhattd@ccf.org. Manuscript received August 29, 2001; revised manuscript received and accepted November 27, 2001.