Suture closure of the femoral arteriotomy following invasive cardiac procedures: a detailed analysis of efficacy, complications, and the impact of early ambulation in 1,200 consecutive, unselected cases.

The purpose of this study was to assess the efficacy and safety of using a percutaneous suture device to close femoral arteriotomies following invasive cardiac procedures. All patients presenting for invasive cardiac procedures performed from the femoral artery were considered for suture closure. Patients were carefully assessed for access site complications, oozing, and the impact of suture closure on the safety of early ambulation. Clinical follow-up at 3-6 months was performed to assess for late complications. Femoral artery suture closures were performed in 1,200 consecutive cases in 1,097 patients. In 12.8% of cases, the patients ambulated within 1 hr. The success rate was 91.2% and the complication rate was 3.4%. Complications included the development of a hematoma (2.1%), the need for vascular surgery (0.6%), retroperitoneal hemorrhage (0.3%), blood transfusion (0.7%), local infection (0.5%), and pseudoaneurysm formation (0.1%). Factors found to be independently predictive of procedural failure were an age > 70 years, an ACT > 300 sec, left femoral artery access, and the performance of primary angioplasty. Follow-up at 3-6 months revealed no major hemorrhagic complications. We conclude that percutaneous suture closure effectively achieves femoral artery hemostasis in patients undergoing invasive cardiac procedures. The technique permits early ambulation and is associated with a relatively low incidence of complication.

Synergy between intracoronary stenting and abciximab in improving angiographic and clinical outcomes of primary angioplasty in acute myocardial infarction.

This study examined 650 consecutive patients who presented with an acute myocardial infarction and were treated with primary angioplasty within 12 hours of symptom onset between August 1995 and December 1998. Patients were placed into 4 treatment groups depending on the adjunctive therapy they received: group 1, percutaneous transluminal coronary angioplasty (PTCA) ("balloon PTCA alone"; n = 220); group 2, PTCA plus intracoronary stent placement ("stent"; n = 128); group 3, PTCA plus abciximab therapy ("abciximab"; n = 104); and group 4, PTCA plus intracoronary stent placement plus abciximab therapy ("stent/abciximab"; n = 198). The patients' clinical characteristics, severity of disease, and total ischemia time on presentation were similar. At baseline, abciximab and stent/abciximab groups had a higher incidence of thrombus on coronary angiography. Postprocedural quantitative coronary analysis showed a significantly larger minimum luminal diameter in the stent and stent/abciximab groups than PTCA alone. Overall, stents were most efficacious in reducing target vessel revascularization rate, whereas abciximab was associated with a higher postprocedural Thrombolysis In Myocardial Infarction-3 trial flow and less "no reflow." The best angiographic result was achieved in the stent/abciximab group. Similarly, the primary combined end point of death, myocardial infarction, and target vessel revascularization at 30 days was the lowest (6.1%) in the stent/abciximab group. The combination of abciximab and stenting in primary angioplasty for acute myocardial infarction is thus synergistic and is associated with improved angiographic and clinical results at 30-day follow-up.

Clinical and angiographic characteristics of exertion-related acute myocardial infarction.

CONTEXT: Vigorous physical exertion transiently increases the risk of acute myocardial infarction (MI), but little is known about the clinical characteristics of exertion-related MI. OBJECTIVE: To compare the clinical and angiographic characteristics of patients who had an exertion-related acute MI vs those who experienced an MI not related to exertion. DESIGN AND SETTING: Prospective observational cohort study of patients with an acute MI referred to a tertiary care hospital for primary angioplasty. PATIENTS: Of 1048 patients with acute MI, 640 (64 who experienced an exertion-related MI and 576 who did not) were selected for treatment with primary angioplasty and admitted between August 1995 and November 1998. MAIN OUTCOME MEASURES: Clinical characteristics of the patients, including their habitual physical activity (determined by the Framingham Physical Activity Index and the Lipid Research Clinic Physical Activity Questionnaire), angiographic findings during coronary angiography, and the relative risk (RR) of MI during exertion. RESULTS: Patients who experienced exertion-related MI were more frequently men (86% vs 68%), hyperlipidemic (62% vs 40%), and smokers (59% vs 37%), were more likely to present with ventricular fibrillation (20% vs 11%), Killip classification III or IV heart failure (44% vs 22%), single-vessel disease (50% vs 28%), and a large thrombus in the infarct artery (64% vs 35%) and were more likely to be classified as having very low or low activity (84% vs 66%). The RR of experiencing an MI during exertion was 10.1 times greater than the risk at other times (95% confidence interval [CI], 1.6-65.6), with the highest risk among patients classified as very low active (RR, 30.5; 95% CI, 4.4-209.9) and low active (RR, 20.9; 95% CI, 3.1-142.1). CONCLUSION: These results show that exertion-related MIs occur in habitually inactive people with multiple cardiac risk factors. These individuals may benefit from modest exercise training and aggressive risk-factor modification before they perform vigorous physical activity.

Enhanced local intracoronary delivery of heparin with the Infiltrator catheter: a comparative study.

The efficacy of local drug delivery in the treatment of coronary artery disease is limited by the relatively low delivery efficiency of the available devices. A unique local drug delivery device, the Infiltrator catheter (InterVentional Technologies, Inc.), has been designed specifically to enhance efficiency by injecting drugs directly into the arterial wall through microports mounted on the balloon surface. The purpose of this study was to assess the efficiency of delivery of this device in the porcine coronary model and to compare it to a previously validated device, the hydrogel balloon (Boston Scientific, Maple Grove, Minnesota). Studies were also performed to assess the pattern of intramural heparin deposition following delivery with the Infiltrator catheter and to assess the effect of the microports on vascular integrity. The efficiency of delivery was significantly greater with the Infiltrator catheter than with the hydrogel balloon (4.5% vs. 0.08%; p = 0.02). Similarly, the absolute amount of intramurally deposited heparin was greater with the Infiltrator (111.3 +/- 38.5 units vs. 2.4 +/- 0.85 units; p = 0.02) despite the fact that more heparin was delivered with the hydrogel catheter. Histologic studies revealed characteristic discrete puncture channels in the vessel wall due to penetration of the microports. Other than this histologic finding, there was no significant difference in the extent of architectural disruption between the Infiltrator and conventional balloon inflations. Fluorescein-labeled heparin studies revealed heparin to be diffusely distributed throughout the vessel wall immediately following delivery with the Infiltrator. We conclude that the Infiltrator catheterOs unique mechanism of delivery improves the efficiency of local drug delivery without excessive vessel wall trauma.

Effect of low grade radiofrequency heating on arterial vasospasm in the porcine model.

Nineteen pigs were studied in order to assess the effect of low grade, radiofrequency-powered, thermal balloon angioplasty on the vasoconstrictor response of peripheral arteries. A mechanical stimulus was used to induce vasospasm. Thermal angioplasty reduced the extent of inducible vasospasm from 79% to 6% compared to nonthermal control inflations, which reduced the vasoconstrictor response from 75% to 60% (P < 0.001). Histologic studies demonstrated that the extent of myocyte necrosis was significantly greater in the thermally treated arteries than in the control vessels (P < 0.01). Thermal balloon angioplasty at 60 degrees C significantly attenuates peripheral arterial vasospasm induced by mechanical trauma in the porcine model. This paralytic effect may be related to the loss of myocytes secondary to thermal necrosis.

Local delivery of c-myb antisense oligonucleotides during balloon angioplasty.

Intraluminal delivery of antisense oligonucleotides to c-myb was assessed following balloon angioplasty in swine peripheral arteries. Successful delivery and intramural persistence of oligonucleotide for over 24 h were demonstrated following angioplasty with hydrogel balloons coated with 32P-labeled antisense. Delivery of fluorescein-labeled antisense demonstrated further localization within the arterial media and intracellularly. Preliminary in vitro studies demonstrated the feasibility of inhibition of porcine lymphocyte proliferation using the murine antisense to c-myb. Twelve iliac or carotid arteries underwent angioplasty with antisense-coated balloons, while the contralateral vessels underwent angioplasty with the same-sized balloons coated with the complementary sense strand. Six to seven days later, dilated arterial segments were surgically isolated. In 10 of 12 vessel pairs, antisense-treated vessels demonstrated less cellular proliferation than did contralateral sense-treated vessels, as assessed by quantitative immunohistochemical staining of proliferating cell nuclear antigen, and smooth muscle cell proliferation was reduced 18% in antisense-treated vessels compared to the contralateral sense-treated vessels (PCNA-positive nuclear area: 7.7 +/- 4.9% vs. 9.3 +/- 5.2%, P < 0.04)-intraluminal delivery of antisense oligonucleotides to c-myb is feasible with a catheter-based system and may reduce smooth muscle cell proliferation following arterial injury.

Local urokinase delivery with the Channel balloon: device safety, pharmacokinetics of intracoronary drug delivery, and efficacy of thrombolysis.

The Channel balloon is a new local drug-delivery catheter that has the dual capability of high-pressure lesion dilation and low-pressure drug infusion. The purpose of this study was to assess the safety and efficacy of this device in the local delivery of urokinase in the porcine model. Three in vivo protocols were performed in 57 anesthetized swine to assess the safety of Channel balloon use in the coronary vasculature, the pharmacokinetics of local urokinase delivery, and the ability of the catheter to lyse intraluminal thrombus. First, safety studies were performed in 18 coronary vessels in 13 pigs to compare angiographic and histologic changes following use of the Channel balloon with conventional balloon angioplasty. Second, intramural deposition of 123I-labeled urokinase was measured in 24 coronary arteries in 20 pigs to assess the efficiency and technical determinants of urokinase delivery and the time course of intramural drug retention. Finally, an in vivo thrombus model was used in 24 pigs to compare the thrombolytic capacity of local urokinase delivery with the Channel balloon in comparison with conventional urokinase infusion techniques. All balloon inflations and drug infusions with the Channel balloon were well tolerated in all animals without adverse angiographic, hemodynamic, or electrical sequelae. Comparative histologic studies with the Channel balloon demonstrated no additional vessel trauma beyond that seen with conventional balloon angioplasty. Between 0.09 and 0.35% of infused urokinase was intramurally deposited, with intracoronary persistence for at least 5 h. Drug infusion pressure did not significantly affect drug deposition, although larger amounts of urokinase were deposited with larger balloon:artery ratios and higher urokinase concentrations. In comparison to conventional systemic and guiding catheter infusions, local delivery of urokinase with the Channel balloon resulted in higher levels of clot dissolution. These studies have demonstrated safe intracoronary use of the Channel balloon in the porcine model. Local infusion of urokinase with this device results in significant intramural drug deposition that persists for at least 5 h. In comparison with conventional thrombolytic techniques, local urokinase delivery with the Channel balloon may result in enhanced intravascular thrombolysis.

Site-specific intracoronary thrombolysis with urokinase-coated hydrogel balloons: acute and follow-up studies in 95 patients.

Conventional balloon angioplasty in the presence of intracoronary thrombus is associated with an elevated risk for acute myocardial infarction, emergency bypass surgery, and death. The purpose of this study was to assess the safety and efficacy of a new technique to treat thrombus-containing stenoses consisting of the local delivery of urokinase directly to the site of intraluminal clot with hydrogel-coated balloons. Ninety-five patients with angiographically apparent intracoronary thrombus were treated with urokinase-coated hydrogel balloons either prior to (n = 74) or following (n = 21) conventional balloon angioplasty. Clinical diagnoses for the study group included acute myocardial infarction in 50 patients, postinfarction angina in 23 patients, and unstable angina in 22 patients. All hydrogel balloons were initially coated with urokinase by immersing the inflated balloon in a concentrated Abbokinase solution (50,000 units/ml) for 60 s. All patients were subsequently treated with drug-coated balloons using a balloon:artery ratio of 1:1, a mean of 2.2 +/- 1.2 inflations, and a mean total inflation time of 7.5 +/- 4.9 min. Use of urokinase-coated balloons resulted in angiographic disappearance of intracoronary thrombus in 78 patients, improvement in 14, and no change in the remaining 3 patients. Following hydrogel balloon use for the entire 95 patients, TIMI flow increased from 1.4 +/- 1.2 to 2.9 +/- 0.4, minimal lumen diameter increased from 0.4 +/- 0.4 to 2.0 +/- 0.6 mm, and thrombus score decreased from 2.0 +/- 0.9 to 0.2 +/- 0.6 (all P < 0.01). Procedural and early in-hospital complications were noted in 7 of the 95 patients (7.4%) and included abrupt closure in 3 patients, distal embolization in 1 patient, no reflow in 1 patient, sidebranch occlusion in 1 patient, and late closure in 1 patient. Two of the 3 patients with abrupt closure and the single patient with late closure required intracoronary stenting to maintain vessel patency. Two of these 7 patients sustained small myocardial infarctions, although no patient required emergency bypass surgery or experienced a procedural death. Late clinical follow-up (mean = 8.3 +/- 6.6 months; range = 2 wk to 29 mo) demonstrated adverse recurrent events in 29 of the 95 patients (30.5%), including death (n = 5), myocardial infarction (n = 2), and recurrence of angina (n = 22). The results of this study suggest that intracoronary thrombolysis can be safely and rapidly achieved by using limited quantities of urokinase delivered directly to the site of intraluminal clot with hydrogel balloons. Use of this technique may result in improved acute outcomes in comparison with conventional techniques currently being used to treat thrombus-containing stenoses.

Treatment of thrombotic saphenous vein bypass grafts using local urokinase infusion therapy with the Dispatch catheter.

Percutaneous treatment of thrombotic stenoses or total occlusions in aged saphenous vein bypass grafts is associated with a significant incidence of complications primarily related to distal embolization. The purpose of this study was to assess the efficacy of local urokinase delivery with the Dispatch catheter prior to balloon angioplasty and/or intragraft stent placement as a new technique of vein graft revascularization. Local urokinase delivery with the Dispatch catheter was performed in 15 saphenous vein grafts (mean age = 11.7 +/- 2.5 yr) in 13 patients with unstable or postinfarction angina. The target lesion was a total occlusion in 5 of the procedures and a severe vein graft stenosis in the remaining 10. In all cases, urokinase was administered directly to the site of the stenosis/occlusion via the Dispatch catheter at 0.5 cc/min and at a concentration of 30,000 units/cc. The mean urokinase infusion time for the 15 procedures was 33 +/- 10 min (range = 10-60 min) and the mean urokinase dose was 495,000 +/- 158,000 units (range = 150,000-900,000 units). Following Dispatch therapy, mean minimal lumen diameter increased from 0.34 +/- 0.32 to 1.81 +/- 0.78 mm (P < 0.01), mean TIMI flow increased from 1.9 +/- 1.4 to 2.8 +/- 0.8 (P < 0.06), and mean thrombus score was reduced from 2.3 +/- 0.6 to 0.3 +/- 0.8 (P < 0.01). Mild no reflow was noted in two cases, although no patient demonstrated angiographic evidence of gross distal embolization. One of the patients with no reflow also demonstrated a small increase in cardiac enzymes. Subsequent balloon angioplasty/stent placement was successful in 14 of the 15 procedures (93% success rate). This preliminary report suggests that pretreatment of thrombotic saphenous vein graft stenoses with local urokinase delivery via the Dispatch catheter may decrease intragraft thrombus and possibly decrease the incidence of vascular complications associated with percutaneous intervention. This technique may allow for recanalization of totally occluded vein grafts with large clot burdens by using significantly less urokinase and shorter drug administration times than conventional infusion protocols.

Local delivery of heparin to balloon angioplasty sites with a new angiotherapy catheter: pharmacokinetics and effect on platelet deposition in the porcine model.

The purpose of this study was to assess the efficacy of local heparin delivery to balloon angioplasty sites in an in vivo porcine model by using a newly designed angiotherapy catheter that allows for prolonged drug infusion while maintaining distal arterial perfusion. Protocols were designed to assess the safety of intracoronary drug delivery, the effect of infusion time and drug concentration on intramural heparin deposition, the distribution of heparin within the arterial wall, the histologic effects of local heparin delivery, the wash-out of intramurally deposited heparin, and the effect of heparin delivery on early platelet deposition following balloon injury in peripheral and coronary vessels. Local intracoronary delivery of heparin was well tolerated in all animals. Between 0.04 and 0.08% of infused heparin was intramurally deposited at the time of drug delivery, with longer infusion durations and higher concentrations of heparin resulting in greater intramural deposition. Autoradiography demonstrated homogenous distribution of heparin throughout the intima, media, and adventitia, with localization in the nuclei, cytoplasm, and extracellular space. Histologic analysis demonstrated no additional vessel trauma from local drug delivery beyond that seen with conventional angioplasty. Wash-out studies demonstrated a biexponential disappearance of intramurally deposited drug, with rapid release of heparin over the first 60 min and persistence of small amounts of drug for at least 7 d. Locally delivered heparin significantly attenuated the deposition of platelets in peripheral vessels, although a similar decrease in platelet deposition in the coronary arteries was not statistically significant. Local delivery of heparin directly to coronary angioplasty sites is possible with the use of a new angiotherapy catheter. Wash-out of heparin from the arterial wall is initially rapid, although drug is detectable for up to 1 wk following delivery. In porcine peripheral arteries, use of this technique significantly decreases early platelet deposition following balloon injury.

Catheter-based local thrombolysis with urokinase: comparative efficacy of intraluminal clot lysis with conventional urokinase infusion techniques in an in vivo porcine thrombus model.

Local delivery of urokinase directly to the site of intraluminal clot using catheter-based technology has recently been introduced as a new technique to treat intracoronary thrombus and thrombus-containing stenoses. The purpose of this study was to compare the efficacy of urokinase therapy administered by local drug-delivery catheters with conventional urokinase-infusion techniques in dissolving intraluminal clot and intramurally depositing drug at the site of arterial injury in an in vivo porcine model. Five techniques of urokinase administration were studied in 65 pigs, including intravenous systemic bolus (1,000,000 units), guiding catheter infusion (500,000 units), local intraluminal infusion with a Roubin catheter (150,000 units), local infusion by the Dispatch catheter (150,000 units), and local delivery by the hydrogel-coated balloon (700 units). All five techniques were initially compared with respect to the quantity of intraluminal lysis of 123I-fibrinogen-labeled thrombus in an in vivo thrombus model. Conventional balloon angioplasty was also assessed in this model as a nonpharmacologic, mechanical control. In addition, all five techniques were compared with respect to the quantity and efficiency of intramural urokinase deposition at coronary angioplasty sites. In the in vivo thrombolysis experiments, the quantity of artificial clot lysis measured 6.8% for systemic therapy, 20.8% for guiding catheter infusion, 25.2% for Roubin catheter infusion, 62.8% for Dispatch catheter infusion, 98.8% for hydrogel balloon delivery, and 53.6% for conventional balloon angioplasty. Both the Dispatch catheter and the hydrogel balloon resulted in more clot lysis than the systemic, guiding catheter, or Roubin catheter approaches (P < 0.05). In comparison with conventional balloon angioplasty, only the hydrogel balloon resulted in higher levels of thrombus dissolution (P < 0.05). In the intramural deposition studies, the efficiency of urokinase delivery was 0.0004% for systemic therapy, 0.004% for guiding catheter infusion, 0.004% for Roubin catheter infusion, 0.08% for Dispatch catheter infusion, and 1.8% for hydrogel balloon delivery. The Dispatch catheter resulted in higher intramural drug levels than did all other techniques (P < 0.05), whereas the efficiency of urokinase deposition was higher with the hydrogel balloon than with all other approaches (P < 0.05). In the porcine model, it is subsequently concluded that local delivery of urokinase by catheter-based techniques can result in more complete lysis of intraluminal thrombus by using similar or lower doses of drug than by using conventional urokinase infusion techniques. Mechanical deformation of thrombus, possibly to increase the surface area available for thrombolysis and to physically disrupt clot, may be an important component of the mechanism of site-specific thrombolysis, particularly with the hydrogel balloon. Local delivery techniques also deposit significant quantities of urokinase at balloon angioplasty sites, creating an intramural reservoir of drug that may result in prolonged local thrombolysis.

Localized delivery of heparin to angioplasty sites with iontophoresis.

Drug delivery by iontophoresis involves the application of an electric field to move selectively charged drug molecules across biological membranes. The purpose of this study was to assess the efficacy of intravascular iontophoresis in the local delivery of heparin to balloon angioplasty sites by using a recently designed iontophoretic catheter. In vivo heparin iontophoresis was assessed in 33 rats and 21 pigs in four protocols designed to measure the technical determinants of intramural drug deposition, the pharmacokinetics and localization of coronary delivery, and the effect of this technique on platelet deposition following balloon injury. First, iontophoresis of 3H-heparin into the aorta of 33 rats was performed to determine the effects of iontophoretic current, iontophoretic membrane balloon initiation pressure, iontophoresis time, and heparin concentration on intramural drug deposition. Second, iontophoresis of 3H-heparin was performed in 16 porcine coronary arteries to quantitate immediate drug delivery and subsequent wash-out over 24 h. Third, iontophoresis of fluorescent heparin was performed in 8 porcine coronary arteries to define intramural localization of locally delivered drug. Fourth, 111In-labeled platelet deposition was measured 1 h following balloon angioplasty and local iontophoretic heparin delivery in 16 porcine carotid and iliac vessels. Contralateral control vessels that were dilated with the same size balloon and treated with iontophoresis of saline served as controls. Rat aortic studies demonstrated that iontophoresis resulted in 13 times more intramural heparin deposition than passive delivery (passive: 0.3 +/- 0.4 microgram, iontophoresis: 4.6 +/- 1.6 micrograms, P < 0.0004). Iontophoretic membrane balloon inflation pressure had no significant effect on intramural drug deposition, but longer iontophoresis times and higher heparin concentrations resulted in higher levels of intramural heparin (P < 0.05). Porcine coronary studies demonstrated successful intramural deposition of heparin in all arteries without adverse electrical or hemodynamic sequelae, with persistence of the drug for at least 24 h. Localization studies demonstrated immediate deposition of fluorescent heparin in the intima and internal elastic lamina, with subsequent rapid diffusion of the drug into the media. Porcine platelet studies demonstrated that heparin iontophoresis decreased platelet deposition following balloon injury by approximately 66% compared with saline-treated control vessels (heparin-treated: 1.46 +/- 2.51 x 10(8), control: 4.27 +/- 7.02 x 10(8), P = 0.001). This study has demonstrated that local intramural heparin delivery is feasible with an intravascular iontophoretic catheter. Following intracoronary heparin iontophoresis in the porcine model, intramural drug is detected for at least 24 h. Local delivery of heparin with this technique significantly decreases early platelet deposition following balloon injury in peripheral porcine arteries.

Maintenance of coronary guidewire position during guide catheter exchange.

Maintaining the position of a guidewire across coronary artery lesions during angioplasty is important to permit rapid and reliable access. This article describes a technique which enables a guide catheter to be replaced while maintaining coronary guidewire position by using an additional, larger guidewire for support to prevent dislodgment of the coronary guidewire.

Recanalization of totally occluded saphenous vein grafts using local urokinase delivery with the Dispatch catheter.

Current techniques for the percutaneous revascularization of totally occluded vein grafts are limited by a low initial success rate, a significant incidence of distal embolization, and a high rate of early graft reclosure. This case report describes two patients in whom graft recanalization was attempted with the combined use of balloon angioplasty/intra-graft stent placement and local urokinase delivery using a new angiotherapy catheter. Successful recanalization was achieved in both patients without major complications, in spite of a large thrombus burden as demonstrated by angiography.

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.

Intracardiac ultrasound imaging during transseptal catheterization.

STUDY OBJECTIVE: The purpose of this study was to assess the feasibility of using small 12.5- or 20-MHz intracardiac ultrasound catheters to image the fossa ovalis and guide transseptal catheterization. DESIGN: The study was performed in three phases. First, in vitro imaging of human autopsy hearts was performed to define the intracardiac ultrasound appearance of the fossa ovalis and transseptal apparatus. Subsequently, the optimum approach for imaging the fossa ovalis in vivo was established in 30 patients. Finally, intracardiac ultrasound imaging was performed during transseptal catheterization of 10 patients undergoing percutaneous mitral commissurotomy. INTERVENTIONS: Intracardiac ultrasound imaging was performed with a 12.5- or 20-MHz single-element mechanical device in which a central imaging core is rotated within a 6F polyethylene sheath. MEASUREMENTS AND RESULTS: In both in vitro and in vivo studies, the fossa ovalis was easily identifiable as a thin membranous region surrounded by the thicker muscular portion of the interatrial septum. Initial in vivo studies established venous access by the femoral route to be superior to the internal jugular approach for catheter introduction. Studies performed during transseptal catheterization established the utility of using the fluoroscopic image of the catheter adjacent to the fossa ovalis to generate a guiding shot for positioning the transseptal apparatus. In addition, distention of the fossa prior to needle perforation could be demonstrated. However, since it was often difficult to track the tip of the needle, actual puncture of the fossa was rarely demonstrated. CONCLUSIONS: Intravascular ultrasound imaging can precisely locate the fossa ovalis in virtually all subjects. It therefore may assist transseptal catheterization.

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.

Treatment of acute stent thrombosis with local urokinase therapy using catheter-based, drug delivery systems: a case report.

Abrupt thrombotic stent closure remains a difficult problem to treat in the cardiac catheterization laboratory. A 63-yr-old white female initially underwent successful placement of a Palmaz-Schatz biliary stent in the proximal RCA following failed coronary angioplasty. One week later, the patient represented with an acute inferior infarction and thrombotic occlusion of the stent site in spite of adequate anticoagulation. A new, local drug infusion catheter (the Dispatch catheter) was placed at the angioplasty site and 150,000 units of urokinase were locally infused, with immediate restoration of normal distal flow and a subsequent marked decrease in angiographic thrombus. A small, residual thrombotic filling defect was further treated with a urokinase-coated hydrogel balloon (Hydro Plus). Following local urokinase delivery with the Dispatch catheter and hydrogel balloon, there was complete resolution of angiographic thrombus with TIMI 3 flow and no evidence of distal embolization or no-reflow. Local urokinase delivery directly to the site of thrombus with catheter-based drug delivery systems may be a useful technique for rapidly lysing intracoronary clot and re-establishing coronary flow in the setting of acute stent thrombosis.

Inhibition of platelet deposition and lysis of intracoronary thrombus during balloon angioplasty using urokinase-coated hydrogel balloons.

BACKGROUND: Conventional balloon angioplasty of intracoronary thrombus is associated with a high incidence of abrupt closure, distal embolization, and no-reflow phenomenon. The purpose of this study was to assess a new technique for treating intracoronary thrombus consisting of the local delivery of urokinase directly to the angioplasty site with urokinase-coated hydrogel balloons. METHODS AND RESULTS: We assessed local urokinase delivery using hydrogel balloons in four protocols. First, we evaluated the pharmacokinetics of urokinase delivery in vitro using 125I-labeled urokinase to measure drug loading onto hydrogel balloons, drug retention by the hydrogel polymer during blood exposure, and drug transfer from the balloon surface to the arterial wall during balloon dilatation. Second, we measured 125I-urokinase washoff from the hydrogel balloon in the intact circulation and intramural drug delivery during in vivo balloon angioplasty in 10 anesthetized New Zealand rabbits. Third, we assessed the effect of local urokinase delivery on 111In-labeled platelet deposition after balloon angioplasty in vivo in 13 porcine carotid or iliac arteries dilated with urokinase-coated balloons and compared them with contralateral control arteries dilated with saline-coated balloons. Finally, we determined the clinical efficacy of urokinase-coated balloons in 15 patients with intracoronary thrombus, including 7 who demonstrated abrupt thrombotic closure after conventional angioplasty. Between 241 and 1509 U urokinase could be loaded onto hydrogel balloons ranging in size from 2 to 8 mm. In vitro and in vivo studies demonstrated that hydrogel balloons absorbed significantly more urokinase and demonstrated less drug wash-off than nonhydrogel balloons (P < .01). Similarly, both in vitro and in vivo studies demonstrated urokinase transfer from the hydrogel to the arterial wall during balloon angioplasty, with greater intramural drug deposition with larger balloons (P < .01). Local urokinase delivery after in vivo porcine angioplasty decreased 111In-labeled platelet deposition by 47% compared with contralateral control vessels (P = .03). Use of urokinase-coated balloons in patients with intracoronary thrombus resulted in thrombus dissolution and reversal of abrupt closure in all cases, without evidence of distal embolization. CONCLUSIONS: With the use of hydrogel-coated balloons, urokinase can be delivered locally to an angioplasty site. This technique decreases platelet deposition after in vivo balloon angioplasty and is efficacious in treating intracoronary thrombus in patients, including those with abrupt thrombotic closure.

Treatment of intracoronary thrombus with local urokinase infusion using a new, site-specific drug delivery system: the Dispatch catheter.

BACKGROUND: The presence of intracoronary thrombus significantly increases the risk of conventional balloon angioplasty because of a high incidence of abrupt closure, distal embolization, and no-reflow phenomenon. The purpose of this study was to assess a new technique for treating intracoronary thrombus consisting of the local delivery of urokinase directly to the angioplasty site with a novel, catheter-based, drug delivery system. METHODS: The Dispatch catheter is a new local, drug-delivery device that allows for the prolonged infusion of therapeutic agents at an angioplasty site while still maintaining distal coronary perfusion. Six patients with angiographic or clinical evidence of intracoronary thrombus were treated with 150,000 units of urokinase over a 30-min period using this device prior to or following conventional balloon angioplasty and/or directional atherectomy. RESULTS: Successful delivery of urokinase directly to the angioplasty site was achieved in all 6 patients without hemodynamic or electrocardiographic compromise. In all six cases, local urokinase therapy resulted in complete dissolution of angiographic intracoronary thrombus and/or reduction of the coronary stenosis. Limited ischemia due to side-branch occlusion by the catheter's coils was noted in one patient. Distal embolization or no-reflow phenomenon were not observed in any case. CONCLUSION: The local drug-delivery catheter used in this study was able to successfully and rapidly achieve intracoronary thrombolysis by delivering limited quantities of urokinase directly to the angioplasty site, while still maintaining distal coronary perfusion. This technique of local, thrombolytic drug delivery may be useful in the percutaneous treatment of intracoronary thrombus and thrombus-containing stenoses.