Enhanced intracoronary thrombolysis with urokinase using a novel, local drug delivery system. In vitro, in vivo, and clinical studies

BACKGROUND: Current pharmacological regimens for treating intracoronary thrombus in the cardiac catheterization laboratory generally involve the administration of thrombolytic agents that result in a systemic fibrinolytic state and/or require prolonged arterial drug infusion. The purpose of the present study was to assess a new technique for treating intracoronary thrombus consisting of the local infusion of limited quantities of urokinase with a novel drug delivery device. METHODS AND RESULTS: THe Dispatch coronary infusion catheter is a new local drug delivery system that allows for the prolonged infusion of therapeutic agents at an angioplasty site while distal coronary flow is maintained. Three experimental protocols were performed to determine the in vitro, in vivo, and clinical efficacy of this device. First, in vitro thrombolysis of fresh, porcine thrombus trapped in a 4-mm plastic tube with a 50% constriction and perfused with 20% porcine plasma was measured. Twenty-three thrombi were weighed before and after no treatment (n = 5), "systemic" urokinase administration (n = 4), local infusion of 150,000 U urokinase with a standard end-hole catheter (n = 4), local infusion of saline with the Dispatch catheter (n = 5), and local infusion of 150,000 U urokinase with the Dispatch catheter (n = 5). Second, 25 porcine coronary arteries in 23 pigs were dilated in vivo with conventional balloon angioplasty and then treated with 123I-labeled urokinase that was administered either by the Dispatch catheter (150,000 U; n = 16), intravenous systemic bolus (1,000,000 U; n = 3), guiding catheter infusion (500,000 U; n = 3), or local end-hole catheter infusion (150,000 U; n = 3). All vessels were subsequently harvested to quantify intramural deposition and subsequent washout of urokinase at the angioplasty site. Finally, 19 patients with angiographic evidence of intracoronary thrombus were treated with local urokinase infusion with the Dispatch catheter either before or after balloon angioplasty or directional atherectomy. In vitro studies demonstrated that infusion of urokinase with the Dispatch catheter decreased thrombus weight by 66% compared with no treatment (-25%), "systemic" urokinase administration (25%), end-hole catheter urokinase infusion (32%), or infusion of saline by the Dispatch catheter (32%) (P < or = .005). In vivo studies demonstrated immediate deposition of 0.12% of the urokinase delivered by the Dispatch catheter to the angioplasty site, compared with 0.0007% with systemic bolus, 0.003% with guiding catheter infusion, and 0.007% with local infusion with an end-hole catheter (P < .001). Urokinase deposited by the Dispatch catheter persisted intramurally for at least 5 hours. Patient studies demonstrated reduction of thrombus-containing stenoses and complete disappearance of intracoronary thrombus in all cases in which 150,000 U urokinase was locally infused over 30 minutes. There was no evidence of abrupt closure, distal embolization, or no reflow in any patient. CONCLUSIONS: Local urokinase delivery with the Dispatch catheter can result in rapid and complete intracoronary thrombolysis using substantially less drug than standard thrombolytic techniques. Intramural deposition of drug with this technique creates a local reservoir of urokinase that may provide prolonged thrombolytic activity at the infusion site.     

Thrombosis in ischemic heart disease

Thrombus formation on a fissured or disrupted atherosclerotic plaque is the main pathogenetic mechanism for the acute coronary syndromes of myocardial infarction and unstable angina. Myocardial infarction results from an acute total occlusion of the artery, while unstable angina is secondary in most cases to mural thrombus formation. Thrombus formation has also been implicated in chronic atherosclerotic disease progression and in restenosis following coronary angioplasty. Therapeutic measures to treat thrombus rely on the ability of drugs to either prevent thrombus extension, dissolve its fibrin component, or prevent further platelet aggregation. Other measures rely on the ability of intracoronary techniques to open coronary arteries. The primary prevention of intracoronary thrombus formation is evolving. Measures to stabilize plaques or to reduce hypercoagulability are being tested or have been tested in recent trials.     

Primary angioplasty using a urokinase-coated hydrogel balloon in acute myocardial infarction during pregnancy

A 38-year-old multigravid white female presented at 16 weeks gestation with an acute inferoposterolateral myocardial infarction. Emergent coronary angiography demonstrated a total proximal occlusion of a large dominant left circumflex artery with a filling defect at the site of the occlusion suggestive of thrombus. Primary angioplasty using a urokinase-coated hydrogel balloon resulted in successful recanalization of the vessel with restoration of normal TIMI Grade III flow and, most notably, apparent complete lysis of the intracoronary thrombus. After a subsequently uneventful pregnancy, a healthy baby was delivered.     

Management of intracoronary thrombosis complicating percutaneous transluminal coronary angioplasty

With technological advances in equipment and increased experience of operators, the success rates of percutaneous transluminal coronary angioplasty (PTCA) now exceed 90%. However, acute periprocural occlusion continues to complicate approximately 6% of all procedures, and many of these occlusions are due to intracoronary (IC) thrombus. Patients at highest risk for this complication include those with acute ischemic syndromes or with angiographically apparent thrombus. These individuals may be candidates for the use of prolonged heparin infusions prior to dilatation, intracoronary thrombolytic therapy, or monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor. All patients undergoing PTCA should receive adequate antiplatelet therapy, including aspirin, and heparin with dosing monitored by activated clotting times (ACT). In addition, some recommend the use of ionic contrast material. When IC thrombus accumulates following intervention, initial therapy should include IC nitroglycerin followed by a combination of redilatation and IC urokinase infusion. Prolonged balloon inflations may be useful, particularly with the use of autoperfusion catheters. Platelet glycoprotein IIb/IIIa receptor antagonists may prove to be beneficial in this situation as well. If the patient's clinical status deteriorates in spite of these measures, emergency coronary artery bypass graft surgery may be required.     

In vivo radiofrequency thermal balloon angioplasty of porcine coronary arteries: histologic effects and safety

The purpose of this study was to assess the safety and histologic effects of radiofrequency thermal balloon angioplasty in the coronary vasculature of normal pigs. Radiofrequency thermal balloon angioplasty was performed in 30 coronary arteries of 16 nonatherosclerotic pigs. Heated inflations were performed at either 50 degrees, 60 degrees, or 70 degrees C for 30 or 60 seconds, and were compared with five nonheated inflations in five additional arteries. All balloon inflations were performed at 2 atm pressure with a balloon/vessel diameter ratio of 1.2 to 1. Heart rate, arterial pressure, and left ventricular pressure were monitored continuously for each animal. A 12-lead ECG, coronary angiography, and two-dimensional transthoracic echocardiography were performed before and 1 hour after each balloon inflation. Each animal was subsequently put to death for postmortem cardiac examination. Heated inflations were well tolerated in 28 of the 30 arteries without significant adverse effects. During one inflation, ventricular fibrillation occurred because of prolonged ischemia from an occlusive guiding catheter. In another artery, a heated inflation resulted in a dissection with a transient decrease in distal coronary flow. Histologic examination revealed a significant increase in wall thinning and elastic fiber straightening with heating at 70 degrees C for both 30 and 60 seconds, and a significant increase in intracoronary thrombus with heating at 70 degrees C for 60 seconds. Depth of periarterial myocardial heat necrosis paralleled the increase in temperature, with an average depth of 166 microns at 50 degrees C, 312 microns at 60 degrees C, and 1031 microns at 70 degrees C. In vivo, radiofrequency coronary angioplasty can be performed relatively safely without significant electrical, hemodynamic, or ischemic changes beyond those seen with conventional nonthermal angioplasty. The extent of heat-induced vessel wall thinning, elastic tissue straightening, intracoronary thrombus formation, and periarterial myocardial necrosis are all related to balloon temperature or duration of heating.     

Intracoronary stenting in acute myocardial infarction

Stent implantation into an infarct-related artery during acute myocardial infarction is generally contraindicated because of the risk of stent thrombosis. We report on 3 patients who had successful stenting for an acute occlusive dissection that developed during direct infarct coronary angioplasty and was refractory to conventional prolonged balloon dilatation, with good long-term clinical and angiographic results. The prerequisites for success include proper premedication, presence of only a minimal amount of thrombus in the infarct-related artery, liberal use of intracoronary thrombolytic therapy, as perfect an angiographic result as possible, as well as careful and aggressive post-stenting anticoagulation.     

Profibrillatory effects of intracoronary thrombus in acute regional ischemia of the in situ porcine heart

BACKGROUND: An intracoronary thrombus during regional ischemia is related to life-threatening arrhythmias. The electrophysiological consequences of a thrombus are unknown. METHODS AND RESULTS: In open chest pigs, regional ischemia was induced by intracoronary injection of a thrombus (protocol 1). In protocol 2, coronary ligation was followed by injection of heparinized blood. Three consecutive episodes of ischemia (10 minutes) and reperfusion (20 minutes) were studied in protocols 3 and 4 (ligation). During the former, an intracoronary thrombus started the third period of ischemia. Multiple (78) local electrograms were recorded simultaneously, and activation patterns were determined. In a first period of ischemia, ventricular fibrillation (during the first 10 minutes) occurred more often after intracoronary thrombosis than during the other protocols (4/7 versus 2/19, P<.05) despite similar size of the ischemic tissue. The incidence of delayed arrhythmias (between 15 and 30 minutes) was not different. Epicardial activation delay was larger 2 to 4 minutes after intracoronary thrombosis compared with ligation. ST elevation was larger with than without a thrombus (2 minutes of ischemia, 12.9+/-4.1 versus 8.2+/-3.0 mV; +/-SD, P<.05). In protocols 3 and 4 the second period and third period of ischemia were similar irrespective of the presence of an intracoronary thrombus. CONCLUSIONS: More conduction slowing underlies the profibrillatory effect of an intracoronary thrombus relative to coronary ligation. After preconditioning with ischemia, the profibrillatory effects are no longer detectable.     

"Rescue" utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty

OBJECTIVES: This study sought to test the effect on thrombus score of the "rescue" utilization of the glycoprotein IIb/IIIa antagonist abciximab given to patients in whom intracoronary thrombus has developed as a complication after percutaneous transluminal coronary angioplasty (PTCA) and to determine its clinical utility. BACKGROUND: Abciximab is effective in the prevention of acute ischemic complications when given prophylactically to patients during high risk PTCA. However, its ability to therapeutically dissolve newly formed intracoronary thrombus occurring as a complication after PTCA is not known. METHODS: We performed an observational study in 29 consecutive patients who received abciximab (0.25 mg/kg body weight intravenous bolus, followed by a 12-h infusion at 10 microg/min) after attempted PTCA caused either the new development or further progression of thrombus. Angiograms were analyzed to determine thrombus score and Thrombolysis in Myocardial Infarction (TIMI) flow grade before and after abciximab. Procedural and clinical success and long-term outcome were also determined. RESULTS: Thrombus score decreased from 3.0 +/- 0.9 (mean +/- SD) to 0.86 +/- 0.92 (p < 0.001), and TIMI flow grade increased from 2.5 +/- 0.7 to 2.9 +/- 0.3 (p = 0.008). No instances of distal embolization or no-reflow were noted. The procedural success (< or = 50% residual stenosis) rate was 97%. The clinical success (procedural success with no in-hospital myocardial infarction, bypass surgery or death) rate was 93%. CONCLUSIONS: Dissolution of thrombus and restoration of TIMI grade 3 flow were readily achieved after administration of abciximab when delivered in a "rescue" manner after the development of thrombosis after PTCA. This novel use of abciximab will need to be validated in randomized trials.     

Mechanisms of luminal enlargement and quantification of vessel wall trauma following balloon coronary angioplasty and directional atherectomy

OBJECTIVES: The purpose of this study was to assess the dual action of lumen enlargement and vessel wall damage following either balloon angioplasty or directional atherectomy, using intracoronary ultrasound, and angioscopy. BACKGROUND: Differences in the mechanisms of action of balloon angioplasty and directional atherectomy may have a significant bearing on the immediate outcome and the restenosis rate at 6 months. METHODS: A total of 36 patients were studied before and after either balloon angioplasty (n = 18) or directional atherectomy (n = 18). Ultrasound measurements included changes in lumen area, external elastic membrane area and plaque burden. In addition, the presence and extent of dissections were assessed to derive a damage score. Angioscopic assessment of the dilated or atherectomized stenotic lesions was translated into semi-quantitative dissection, thrombus and haemorrhage scores. RESULTS: Atherectomy patients had a larger angiographic vessel size compared with the angioplasty group (3.55 +/- 0.46 mm vs 3.00 +/- 0.64 mm, P < 0.05); however, minimal lumen diameter (1.18 +/- 0.96 mm vs 0.85 +/- 0.49 mm) and plaque burden (17.04 +/- 3.69 vs 15.23 +/- 4.92 mm2) measurements did not differ significantly. As a result of plaque reduction, atherectomy produced a larger increase in luminal area than the angioplasty group (5.80 +/- 1.78 mm2 vs 2.44 +/- 1.36 mm2, P < 0.0001). Lumen increase after angioplasty was the result of 'plaque compression' (50%) and wall stretching (50%). Additionally, in both groups there was indirect angioscopic evidence of thrombus 'microembolization' as an adjunctive mechanism of lumen enlargement. Angioscopy identified big flaps in six and small intimal flaps in 11 of the atherectomized patients as compared with five and 12 patients in the angioplasty group. Changes in thrombus score following both coronary interventions were identical (0.72 +/- 3.42 points atherectomy vs -0.38 +/- 3.27 points balloon angioplasty, ns). CONCLUSIONS: Lumen enlargement after directional atherectomy is mainly achieved by plaque removal (87%), whereas balloon dilation is the result of vessel wall stretching (50%) and plaque reduction (50%). Despite the fact that the luminal gain achieved by directional atherectomy is twice that achieved with balloon angioplasty, the extent of trauma induced by both techniques seems to be similar.     

Intravascular ultrasound assessment of direct percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction

BACKGROUND: Acute myocardial infarction is caused by sudden thrombotic occlusion of the coronary artery due to a previous rupture of atherosclerotic plaque. OBJECTIVE: To use intracoronary ultrasound measurements to evaluate lumen and plaque changes in patients with acute myocardial infarction. METHODS: Patients (n = 103) with acute myocardial infarction who had been scheduled to undergo primary percutaneous transluminal coronary angioplasty (PTCA) were selected. Both before and after successful coronary angioplasty, intracoronary 30 MHz ultrasound studies were performed using a 3.5F monorail catheter. The ultrasound catheter was successfully advanced into the occluded vessel segment without major complications prior to PTCA in 79 of 103 (76.7%) patients and after PTCA in 88 of 103 (85.3%) patients. RESULTS: The plaques were eccentric in 66 patients (83.5%). The plaque morphology was purely low echogenic in 14 (17.7%), highly echogenic in six (7.6%) and mixed in 59 (74.7%) patients. Partial (59 of 79, 74.7%) or ring-like calcification (3 of 79, 3.8%) was observed in 62 patients (78.5%). Plaque fissuring or dissection was detected prior to PTCA in 25 patients (31.7%). Coronary angioplasty successfully enlarged the inner luminal area from 2.1 +/- 0.7 to 7.4 +/- 1.9 mm2 (P < 0.01), whereas the plaque-thrombus area decreased significantly (13.8 +/- 1.7 mm2 before and 9.0 +/- 1.9 mm2 after PTCA; P < 0.01). The total vessel area remained virtually constant (15.9 +/- 1.9 mm2 before and 16.4 +/- 2.5 mm2 after PTCA, NS). PTCA-induced plaque rupture or dissection was observed in only 13 (16.5%) patients. CONCLUSION: Intracoronary ultrasound imaging can be performed safely and successfully prior and subsequent to PTCA in selected patients with acute myocardial infarction. Early reperfusion via PTCA seems to be attributable to a significant reduction in the amount of low-echogenic plaque and thrombus material, whereas factors like balloon-induced dissection and stretching of vessels play only a minor role.     

Pharmacologic myocardial protection during percutaneous transluminal coronary angioplasty by intracoronary application of dipyridamole: impact on hemodynamic function and left ventricular performance

OBJECTIVES: The aim of this study was to investigate whether intracoronary infusion of dipyridamole represents a suitable tool for preventing deterioration of left ventricular performance and hemodynamic function during percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Coronary angioplasty represents a suitable model for establishing myocardial ischemia in humans. Balloon inflation is usually accompanied by significant deterioration in left ventricular systolic and diastolic properties. A brief episode of ischemia followed by reperfusion, termed preconditioning, has been identified as a mechanism for rendering the myocardium more resistant to ischemia. Adenosine is considered an important mediator of preconditioning. Dipyridamole is an important drug that interferes with myocardial adenosine metabolism by inhibiting its cellular reuptake. METHODS: In 20 patients undergoing elective coronary angioplasty of a major vessel, assessment of angiographic left ventricular performance and hemodynamic variables was performed before, during and after PTCA. Patients were randomly allocated to pretreatment with intracoronary infusion of dipyridamole before percutaneous transluminal coronary angioplasty (10 patients) or conventional pretreatment without dipyridamole (10 patients). RESULTS: Dipyridamole pretreatment resulted in significant preservation of systolic and diastolic left ventricular performance during percutaneous transluminal coronary angioplasty, as documented by an unaffected global ejection fraction (vs. a deterioration of 29.2% with conventional pretreatment, p < 0.01) and an increment in diastolic stiffness of only 12.7% (vs. an increment of 57.3% with conventional pretreatment, p < 0.01). Apart from one instance of coronary steal phenomenon, no significant side effects of dipyridamole infusion could be detected. CONCLUSIONS: It is concluded that intracoronary application of dipyridamole may result in the induction of myocardial preconditioning by improving systolic and diastolic ventricular performance during percutaneous transluminal coronary angioplasty, thereby potentially reducing the risk of the angioplasty procedure.     

Systemic and translesional activation of coagulation, fibrinolytic, and inhibitory systems in candidates for coronary angioplasty: basal state and effect of successful dilation

OBJECTIVES: Thrombosis is a major contributor to complications associated with coronary interventions. It is unclear whether patients who have undergone angioplasty are predisposed to thrombus formation because of underlying perturbations in their hemostatic equilibrium. METHODS: Concentration or activity was measured for 14 plasma proteins involved in the coagulation, fibrinolytic, and inhibitory systems. Baseline systemic measurements were compared between patients undergoing balloon angioplasty (n = 15) and normal subjects (n = 32), with sampling repeated at the end of the procedure. To better assess the local hemostatic environment near the site of dilation, intracoronary arterial samples were also obtained just proximal and distal to the dilated stenosis. RESULTS: Multiple differences in measured coagulation proteins were found at baseline between the angioplasty candidates and control subjects, including higher mean concentration of plasma fibrinogen (P <.001) and lower high-molecular-weight kininogen concentration (P <.01) and factor XII activity (P <.01). Concentrations of the inhibitory proteins antithrombin III and protein S also differed significantly (P <.001 and P <.01, respectively), with a trend toward lower protein C concentration as well (P <.05). Finally, heightened fibrinolysis was suggested by a marked increase in mean plasma d-dimer concentration in the angioplasty candidates (293 +/- 191 ng/mL vs 116 +/- 31 ng/mL, P <.01), with a more modest increase in tissue plasminogen activator (P <.05) and decrease in alpha2-antiplasmin (P <.001). Importantly, none of the parameters obtained during the procedure differed significantly from samples obtained before and after angioplasty, and no translesional gradients were observed. CONCLUSIONS: Patients with active ischemic syndromes who are considered candidates for coronary angioplasty demonstrate significant and multiple alterations in their coagulation, inhibitory, and fibrinolytic systems. However, no further changes were observed during coronary dilation, either systemically or locally, after pretreatment with typical doses of heparin and aspirin.     

Prospective, randomized trial of prolonged intracoronary urokinase infusion for chronic total occlusions in native coronary arteries

OBJECTIVES: The purpose of this study was to determine the safety and efficacy of three dosing regimens of intracoronary urokinase for facilitated angioplasty of chronic total native coronary artery occlusions. BACKGROUND: Percutaneous transluminal coronary angioplasty of chronically occluded (>3 months) native coronary arteries is associated with low initial success secondary to an inability to pass the guide wire beyond the occlusion. METHODS: Patients were enrolled if a chronic total occlusion >3 months old could not be crossed with standard angioplasty equipment. Of the 101 patients enrolled, 41 had successful guide wire passage and were excluded from urokinase treatment. The remaining 60 patients were randomized to receive one of three intracoronary dosing regimens of urokinase over 8 h (group A = 0.8 million U; group B = 1.6 million U; group C = 3.2 million U), and angioplasty was again attempted after completion of the urokinase infusion in 58 patients. RESULTS: Coronary angioplasty was successful in 32 patients (53%) (group A 52%, group B 50%, group C 59%, p = 0.86). This study had a 90% power to detect at least a 50% difference between dosing groups at alpha 0.05. Bleeding complications requiring blood transfusion did not differ significantly among the dosing groups (A 0%, B 15%, C 6%, p = 0.14), although major bleeding episodes were less common in group A (p < 0.05). There were no major procedural or in-hospital complications. Angiographic follow-up in 69% of the patients with successful angioplasty revealed target vessel patency in 91% but an angiographic restenosis rate of 59%. CONCLUSIONS: A prolonged supraselective intracoronary infusion of urokinase can be safely administered and may facilitate angioplasty of chronic total occlusions. Lower doses of urokinase are equally effective and result in fewer bleeding complications than do higher dosage regimens. Vessel patency is frequently maintained, but restenosis remains a problem.     

Intracoronary artery thrombus formation in unstable angina: a clinical, biochemical and angiographic correlation

OBJECTIVES: We examined the relation between the level of urinary fibrinopeptide A and the presence of angiographic intracoronary thrombus in patients with unstable angina to determine whether this marker predicts active thrombus formation. BACKGROUND: Although it is known that thrombus plays a role in acute ischemic syndromes, a noninvasive method to predict its presence in individual patients with unstable angina has not been determined. Fibrinopeptide A is a polypeptide cleaved from fibrinogen by thrombin and thus is a sensitive marker of thrombin activity and fibrin generation. METHODS: Angiographic thrombus, graded 0 to 4, and the presence of ST segment depression or T wave inversions, or both, on the electrocardiogram (ECG) were related to fibrinopeptide A levels in 24 patients with rest angina of new onset, 18 with crescendo angina, 19 with stable angina and 9 with chest pain but without coronary artery disease. All patients had chest pain within the 24 h of sample acquisition. RESULTS: The angiographic incidence of thrombus was significantly higher in patients with new onset of rest angina (67%, p < 0.001) and crescendo angina (50%, p < 0.001) as were fibrinopeptide A levels (p = 0.002). Fibrinopeptide A levels correlated significantly (p < 0.001) with the presence of a filling defect (grade 4 intracoronary thrombus) or contrast staining (grade 3). All patients with fibrinopeptide A > or = 8 ng/mg creatinine showed grade 3 to 4 thrombus and 15 of 16 patients with levels > or = 6.0 ng/mg creatinine exhibited angiographic evidence of thrombus (13 with grades 3 to 4). Patients with reversible ST changes on the ECG had significantly higher levels of fibrinopeptide A (p < 0.001), and ST changes correlated significantly with the presence of angiographic thrombus (p < 0.001). Nonetheless, a significant minority of patients with unstable angina had neither angiographic nor biochemical evidence of thrombus. CONCLUSIONS: Elevated fibrinopeptide A levels in unstable angina reflected active intracoronary thrombus formation and were present in patients with angina of new onset as well as crescendo angina. Reversible ST changes are accompanied by thrombin activity and angiographic thrombus formation. However, a sizable percentage of patients with unstable angina had no evidence of thrombus and these patients may have had transient platelet aggregation without fibrin thrombus formation.     

The use of relational databases in the transition from quality assurance to continuous quality improvement: a clinical practice model

BACKGROUND AND OBJECTIVE: The solid-state, mid-infrared holmium:YAG laser (2.1 microm wavelength) is a relatively new percutaneous device that has recently been evaluated in a multicenter study. Because of its unique wavelength and photoacoustic effects on atherosclerotic plaques, this laser may be useful in treatment of symptomatic patients with coronary artery disease. This study sought to evaluate the safety and efficacy of mid-infrared laser angioplasty in the treatment of coronary artery lesions. PATIENTS AND METHODS: Laser angioplasty was performed on 2,038 atherosclerotic lesions in 1,862 consecutive patients with a mean age of 61 +/- 11 years. Clinical indications included unstable angina (69%), stable angina (20%), acute infarction (6%), and positive exercise test (5%). Complex lesion morphology included eccentricity (62%), thrombus (30%), total occlusion (27%), long lesions (14%), and saphenous vein grafts (11%). RESULTS: This laser catheter alone successfully reduced stenosis (>20%) in 87% of lesions. With adjunct balloon angioplasty, 93% procedural success was achieved. The presence of thrombus within the target lesion was a predictor of procedural success (OR = 2.0 [95% confidence interval 2.0, 4.0], P = .04). Bifurcation lesions (OR = 0.5 [95% confidence interval 0.2, 1.0], P = .05) and severe tortuosity of the treated vessel (OR = 0.4 [95% confidence interval 0.2, 0.9], P = .02) were identified as significant predictors of decreased laser success. Calcium within the lesion was associated with reduced procedural success (OR = 0.57 [95% confidence interval 0.34, 0.97], P = .03), and calcified lesions required significantly more energy pulses than noncalcified lesions (119 +/- 91 pulses vs. 101 +/- 86 pulses, respectively, P = .0002). Complications included in-hospital bypass surgery 2.5%, Q-wave myocardial infarction 1.2%, and death 0.8%. Perforation occurred in 2.2% of patients; major dissection in 5.8% of patients, and spasm in 12% of patients. No predictor of major complications was identified. Six-month angiographic restenosis was documented in 54% of patients, and clinical restenosis occurred in 34% of patients. CONCLUSION: Mid-infrared laser has a safety profile similar to that of other debulking devices. This laser may be useful in select patients presenting with acute ischemic syndromes associated with intracoronary thrombus; however, like other coronary lasers, it is limited by the need for adjunctive balloon angioplasty and/or stenting to achieve adequate final luminal diameter. No beneficial effects on reducing 6-month restenosis rates were observed.     

Medullary mechanism of the inhibition on renal sympathetic efferent activities by stimulation of the cervical vagal afferent nerve in rabbits

The presence of angiographic evidence of thrombus is generally thought to be a contraindication to coronary stent placement. This report describes four patients in whom angiographic thrombus was lysed using the Dispatch infusion catheter prior to coronary stenting. Urokinase was infused via the Dispatch catheter with resolution of angiographic evidence of thrombus in all cases. No complications were encountered using this technique, and all patients had excellent angiographic results after stenting. We conclude that lysis of intracoronary thrombus using the Dispatch infusion catheter is feasible and appears safe in this small study. Further trials are needed to determine if this technique reduces the acute stent thrombosis rate compared to other techniques for stent deployment in the presence of angiographic evidence of thrombus.     

IV vancomycin-oral ciprofloxacin: a safe and efficient therapeutic protocol for CAPD peritonitis (preliminary report)

We report on a case of intractable recurrent ventricular fibrillation that responded poorly to antiarrhythmic medication and balloon angioplasty, but resolved instantaneously following intracoronary stenting.     

Reducing bias in language assessment: processing-dependent measures

OBJECTIVES: This study sought to correlate angiographically detected complex lesions and intracoronary thrombus with the severity of clinical presentation in unstable angina (UA). BACKGROUND: Unstable angina is usually related to acute thrombosis superimposed on a disrupted plaque. Complex and thrombotic lesions are more prevalent in UA and have been associated with a worse prognosis. The highest levels of the Braunwald classification of UA (III = rest angina within 48 h of presentation; C = postinfarction angina; and c = angina refractory to maximal medical therapy) can be used to assess the severity of clinical presentation, but they have not been directly correlated with thrombotic and complex lesions. METHODS: We conducted a prospective study of 284 patients with UA who underwent cardiac catheterization. A single angiographer with no knowledge of the clinical classifications interpreted all angiograms. Culprit lesions identified in 200 patients were classified as simple or complex. Complex lesions included the categories complex morphology, intracoronary thrombus (ICT) or total occlusion. Lesions were also quantitatively analyzed, and Thrombolysis in Myocardial Infarction (TIMI) flow was assessed. Univariate and multivariate logistic regression analyses of the angiographic findings were performed controlling for all cardiac risk factors, previous angioplasty or bypass surgery and multivessel disease, and we sequentially compared Braunwald classes III, C and c with classes < III, < C and < c, respectively. RESULTS: Class III was associated with complex lesions (p = 0.04) and decreased TIMI flow (p = 0.03). Class C angina correlated with complex lesions (p = 0.04), ICT (p = 0.005) and decreased TIMI flow (p = 0.03). Class c angina was associated with ICT (p = 0.02). The degree of stenosis by quantitative angiography was not associated with any particular Braunwald class. CONCLUSIONS: Recent rest pain and refractory or postinfarction UA, or both, are strongly associated with the general category of complex lesions and specifically with angiographically detected ICT and decreased TIMI flow.     

Subacute stent thrombosis: evolving issues and current concepts

During percutaneous coronary revascularization, intracoronary stents are effective in the treatment of abrupt vessel closure and improvement of suboptimal angioplasty results, and compared to balloon angioplasty, they reduce stenosis recurrence. Opposing these benefits, subacute thrombosis of stents is associated with a substantial increase in periprocedural morbidity and mortality. To review factors associated with stent thrombosis and to study the impact of evolving procedural techniques on the incidence of stent thrombosis, we reviewed all English articles from MEDLINE (1988 to 1995) with key words "stent" and "thrombosis." Stent registry data and recent abstracts from scientific meetings were also reviewed. Factors related to the clinical setting, the lesion, the stent and the procedural technique that affect the risk of stent thrombosis were identified. Sixty clinical studies were reviewed and include 7,914 patients receiving intracoronary stents. Studies were separated into those reporting stents placed emergently or electively without adjunct high-pressure balloon inflations, stents placed in saphenous vein graft conduits, and stents placed with high-pressure balloon inflations but without subsequent oral anticoagulants. Overall, subacute thrombosis was substantially higher in stents placed emergently (10.1%) compared to those placed electively (4.3%). Among contemporary trials employing high-pressure balloon inflations, the rate of stent thrombosis appears markedly lower (1.3%) despite reduced postprocedural anticoagulation. Taken together, these studies suggest factors associated with a heightened risk of stent thrombosis, many of which can be avoided with proper case selection and contemporary techniques.     

Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. Restenosis Stent Study Group

BACKGROUND: Intracoronary stenting reduces the rate of restenosis after angioplasty in patients with new coronary lesions. We conducted a prospective, randomized, multicenter study to determine whether intracoronary stenting, as compared with standard balloon angioplasty, reduces the recurrence of luminal narrowing in restenotic lesions. METHODS: A total of 383 patients who had undergone at least one balloon angioplasty and who had clinical and angiographic evidence of restenosis after the procedure were randomly assigned to undergo standard balloon angioplasty (192 patients) or intracoronary stenting with a Palmaz-Schatz stent (191 patients). The primary end point was angiographic evidence of restenosis (defined as stenosis of more than 50 percent of the luminal diameter) at six months. The secondary end points were death, Q-wave myocardial infarction, bypass surgery, and revascularization of the target vessel. RESULTS: The rate of restenosis was significantly higher in the angioplasty group than in the stent group (32 percent as compared with 18 percent, P= 0.03). Revascularization of the target vessel at six months was required in 27 percent of the angioplasty group but in only 10 percent of the stent group (P=0.001). This difference resulted from a smaller mean (+/-SD) minimal luminal diameter in the angioplasty group (1.85+/-0.56 mm) than in the stent group (2.04+/-0.66 mm), with a mean difference of 0.19 mm (P=0.01) at follow-up. Subacute thrombosis occurred in 0.6 percent of the angioplasty group and in 3.9 percent of the stent group. The rate of event-free survival at 250 days was 72 percent in the angioplasty group and 84 percent in the stent group (P=0.04). CONCLUSIONS: Elective coronary stenting was effective in the treatment of restenosis after balloon angioplasty. Stenting resulted in a lower rate of recurrent stenosis despite a higher incidence of subacute thrombosis.