Kenneth Ouriel

A Comparison of Recombinant Urokinase with Vascular Surgery as Initial Treatment for Acute Arterial Occlusion of the Legs

BACKGROUND Recent controlled trials suggest that thrombolytic therapy may be an effective initial treatment for acute arterial occlusion of the legs. A major potential benefit of initial thrombolytic therapy is that limb ischemia can be managed with less invasive interventions. METHODS In this randomized, multicenter trial conducted at 113 North American and European sites, we compared vascular surgery (e.g., thrombectomy or bypass surgery) with thrombolysis by catheter-directed intraarterial recombinant urokinase; all patients (272 per group) had had acute arterial obstruction of the legs for 14 days or less. Infusions were limited to a period of 48 hours (mean [+/-SE], 24.4+/-0.86), after which lesions were corrected by surgery or angioplasty if needed. The primary end point was the amputation-free survival rate at six months. RESULTS Final angiograms, which were available for 246 patients treated with urokinase, revealed recanalization in 196 (79.7 percent) and complete dissolution of thrombus in 167 (67.9 percent). Both treatment groups had similar significant improvements in mean ankle-brachial blood-pressure index. Amputation-free survival rates in the urokinase group were 71.8 percent at six months and 65.0 percent at one year, as compared with respective rates of 74.8 percent and 69.9 percent in the surgery group; the 95 percent confidence intervals for the differences were -10.5 to 4.5 percentage points at six months (P=0.43) and -12.9 to 3.1 percentage points at one year (P=0.23). At six months the surgery group had undergone 551 open operative procedures (excluding amputations), as compared with 315 in the thrombolysis group. Major hemorrhage occurred in 32 patients in the urokinase group (12.5 percent) as compared with 14 patients in the surgery group (5.5 percent) (P= 0.005). There were four episodes of intracranial hemorrhage in the urokinase group (1.6 percent), one of which was fatal. By contrast, there were no episodes of intracranial hemorrhage in the surgery group. CONCLUSIONS Despite its association with a higher frequency of hemorrhagic complications, intraarterial infusion of urokinase reduced the need for open surgical procedures, with no significantly increased risk of amputation or death.

Contemporary Analysis of Descending Thoracic and Thoracoabdominal Aneurysm Repair : A Comparison of Endovascular and Open Techniques

Background— Endovascular repair of thoracic aneurysm has demonstrated low risks of mortality and spinal cord ischemia (SCI), but few large series have been published on endovascular thoracoabdominal aneurysm repair, and reports suffer from a lack of accurate comparison with similar open surgical procedures. Methods and Results— A consecutive cohort of patients with thoracic and thoracoabdominal aneurysms treated electively with endovascular repair (ER) or surgical repair (SR) techniques between 2001 and 2006 were analyzed. The association between repair technique and SCI was evaluated with univariable analysis. Adjustments for potential confounders and for the propensity to receive ER or SR were also performed in multivariable analysis. A total of 724 patients (352 ER, 372 SR) underwent repair. The mean age was 67 years, and 65% were male. ER patients were on average 9 years older (P<0.001), had more comorbid conditions, and more frequently had prior distal repair (P<0.001) or underwent a type I or IV repair. SR patients more commonly had chronic dissection or required type II or type III repairs (P<0.001). Mortality at 30 days (5.7% ER versus 8.3% SR, P=0.2) and 12 months (15.6% ER versus 15.9% SR, P=0.9) was similar. A borderline difference in SCI was found between repair techniques: 4.3% of ER and 7.5% of SR patients (P=0.08) had SCI. In patients with ER, prior distal aortic operation was associated with the development of SCI in univariable analysis (odds ratio 4.1, 95% confidence interval 1.4 to 11.7). Multivariable analysis showed that the type of required repair (type I, II, III, or IV) was the primary factor associated with the development of SCI in ER and SR patients. Conclusion— No significant difference in the incidence of mortality or SCI was found between ER and SR techniques. The strongest factor associated with SCI remains the extent of the disease. Further studies are indicated to compare ER with patients considered eligible for SR.

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism : The SEATTLE II Study

OBJECTIVES This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

Should patients with challenging anatomy be offered endovascular aneurysm repair

OBJECTIVES Treatment of abdominal aortic aneurysm is controversial in patients at high physiologic risk for open repair and high anatomic risk for endovascular repair. We compared outcome in patients at high risk because of anatomy (short or angulated neck), severe occlusive disease, or bilateral iliac aneurysms (group A) with outcome in patients at low risk (group B). MATERIAL AND METHODS Patients at high anatomic risk who underwent treatment between October 1998 and March 2002 with the Zenith endovascular graft (group A) were compared with patients at low anatomic risk enrolled in a prospective multicenter trial (group B). Variables compared included overall mortality, need for secondary interventions, development of endoleak, and change in aneurysm sac diameter. The chi(2) test, Student t test, and proportions analysis were used to assess the data. RESULTS Data for 493 patients (group A, 141; group B, 352) were evaluated. Mean follow-up was 9 months (range, 1-24 months). Perioperative mortality was similar for groups A and B (0.7% vs 1%). Frequency of endoleak was higher in patients with high-risk anatomy (25% vs 11%), but not significantly so (P >.06). The rate of aneurysm shrinkage, even in the absence of endoleak, was slower in group A (P <.05). CONCLUSIONS In physiologically challenged patients at higher anatomic risk for endovascular aneurysm repair, initial mortality rate is similar to that in patients at lower risk. Short-term technical results are acceptable. Decreased long-term survival (largely unrelated to the procedure), slightly higher frequency of endoleak, and a lower rate of sac shrinkage may temper enthusiasm for endovascular repair in this subgroup. Risks of repairing aneurysms in this patient population must be viewed in the context of expected results of intervention or medical observation.

Transfemoral endovascular aortic graft placement

PURPOSE The purpose of this study was to develop an endovascular system for transfemoral placement of straight aortic grafts and bifurcated aortoiliac grafts. METHODS Both types of graft consist of barbed, self-expanding stents attached to a woven polyester fabric. Survival studies of straight-graft function were performed in six large mongrel dogs. Digital subtraction fluoroscopic equipment was used to guide insertion and record angiograms at 0, 1, and 3 months. Bifurcated grafts were inserted in an additional eight dogs, four with distal stents and four without. Straight grafts were inserted into six cadaveric aortas (five atherosclerotic and one aneurysmal; age 68.7 + 5.7 years) to assess stent attachment. RESULTS Angiograms obtained immediately after straight-graft insertion showed placement to be within 4.6 + 1.6 mm of the intended level. Follow-up angiograms at 1 and 3 months showed no migration, no leakage, and patency of all six grafts. After bifurcated graft insertion there were no angiographic signs of perigraft leakage, with or without distal stents. The mean force required to displace straight grafts 10 mm from their original position in cadaveric aortas was 1388 + 127 g. CONCLUSION These preliminary results show that straight and bifurcated endovascular grafts can be positioned accurately and securely in the abdominal aorta.

Thrombolysis or peripheral arterial surgery: Phase I results

PURPOSE Thrombolytic therapy is widely used in the treatment of peripheral arterial occlusion, but prospective, randomized comparisons with standard therapy remain few. A multicenter trial of thrombolysis or peripheral arterial surgery (TOPAS) was organized to compare critically the use of recombinant urokinase (rUK) or surgery for the initial treatment of acute lower-extremity ischemia. Phase I of the trial was designed as a dose-ranging trial to evaluate the safety and efficacy of three doses of rUK in comparison with surgery. METHODS In a multicenter, prospective, double-blind comparison, 213 patients who had acute lower-extremity ischemia for 14 days or fewer were randomized to one of two groups. The first group received one of three dosages of rUK (catheter-directed at 2000, 4000, or 6000 IU/min for 4 hours, then 2000 IU/min to a maximum of 48 hours). The second group underwent surgery. Successful thrombolysis was followed by surgical or endovascular interventions when anatomic lesions responsible for the occlusion were unmasked. Patients were followed-up for 1 year; data were evaluated on an intent-to-treat basis. RESULTS The 4000 IU/min rUK dosage was chosen as the most appropriate thrombolytic regimen because it maximized lytic efficacy against the risk of bleeding. Complete (> 95%) lysis of thrombus was achieved in 71% of the 49 patients who were randomized to the 4000 IU/min group, with a mean infusion time of 23 hours. In contrast, complete lysis was achieved in 67% of patients who received 2000 IU/min and in 60% of patients who received 6000 IU/min. Hemorrhagic complications occurred in 2% of the 4000 IU/min group versus 13% of the 2000 IU/min group (p = 0.05) and 16% of the 6000 IU/min group (p = 0.03). In a comparison of the 4000 IU/min group with the surgical group, the 1-year mortality rate (14% vs 16%) or amputation-free survival rate (75% vs 65%) did not differ significantly. The frequency and magnitude of surgery in the patients randomized to rUK were decreased (p < 0.001). CONCLUSION The preliminary results suggest that an initial rUK dose of 4000 IU/min is safe and efficacious in the treatment of acute lower-extremity ischemia. rUK therapy is associated with limb salvage and patient survival rates similar to those achieved with surgery, concurrent with a reduced requirement for complex surgery after thrombolytic intervention.

Percutaneous AngioJet Thrombectomy in the Management of Extensive Deep Venous Thrombosis

PURPOSE This study was undertaken to evaluate the efficacy of a percutaneous mechanical thrombectomy (PMT) device for rapid thrombus removal following deep venous thrombosis (DVT). MATERIALS AND METHODS Over a 37-month period, 17 patients (14 women; mean age, 41 y +/- 20) with extensive DVT were treated with initial attempts at PMT with use of the AngioJet rheolytic thrombectomy device. Sites of venous thrombosis included lower extremities in 14 patients and upper extremity and brachiocephalic veins in three. The etiology for venous thrombosis was malignancy in seven, idiopathic etiology in three, May-Thurner syndrome and immobilization in three each, and oral contraceptive use and hypercoagulable disorder in one each. The primary endpoint was venographic evidence of thrombus extraction. Perioperative complications, mortality, and recurrence-free survival were also evaluated. RESULTS After PMT, four of 17 patients (24%) had venographic evidence of >90% thrombus removal, six of 17 (35%) had 50%-90% thrombus removal, and seven of 17 (41%) had <50% thrombus extraction. Adjunctive thrombolytic therapy was used in nine of 13 patients with <90% thrombus extraction by PMT; six patients (35%) had contraindications to pharmacologic thrombolytic therapy. An underlying lesion responsible for the occlusion was uncovered in 10 patients (59%). Significant improvement in clinical symptoms was seen in 14 of 17 patients (82%). No complications were noted directly relating to the use of the AngioJet thrombectomy catheter. None of the patients were lost to follow-up during a mean of 8.9 months +/- 5.3 (range, 2-21 months). At 4 and 11 months, recurrence-free survival rates were 81.6% and 51.8%, respectively. CONCLUSION PMT with adjunctive thrombolytic therapy is a minimally invasive, low-risk therapeutic option in patients with extensive DVT, associated with clinical benefits including thrombus removal, patency, and relief of symptoms.

Ultrasound-Guided Thrombin Injection for the Treatment of Postcatheterization Pseudoaneurysms

BackgroundThis prospective study was designed to assess the safety and efficacy of using bovine thrombin injection to treat pseudoaneurysms. Methods and ResultsFrom April 1998 through December 1999, 70 pseudoaneurysm were injected with bovine thrombin under the guidance of color duplex ultrasound. The most superficial pseudoaneurysm chamber was entered with a 1.5-inch, 19- to 22-gauge or spinal needle. Bovine thrombin, in a 1000 U/cc solution, was injected into the chamber. A total of 36 women and 34 men underwent ultrasound-guided thrombin injection (UGTI). Their mean age was 69.5 years. Most pseudoaneurysms were associated with diagnostic cardiac catheterization or percutaneous coronary intervention (80%). Two pseudoaneurysms arose from the brachial artery; the remainder were in the groin. Twenty-one patients were being treated with either heparin or warfarin, and the majority of the others were on antiplatelet therapy with aspirin or clopidogrel. UGTI was successful in 66 of the 70 patients (94%). The first patient in the series had 2 attempts at thrombin injection and refused further attempts. Two patients had undergone stent graft placement and had short, wide tracts. Both of these patients required surgical repair of their pseudoaneurysms. The fourth patient had a nearly complete pseudoaneurysm thrombosis and was lost to follow-up on discharge. No arterial thrombotic events occurred. One patient had a soleal vein thrombosis in the ipsilateral leg. ConclusionsUGTI was safe and effective in 94% of patients with postcatheterization pseudoaneurysms. Anticoagulant use did not hinder successful thrombosis. UGTI should be the initial treatment of choice for patients with postcatheterization pseudoaneurysms.

Adenocarcinoma of the small intestine

Sixty-five patients with adenocarcinoma of the small intestine were encountered over a 31 year period. The duodenum was the most common location, with a decreasing frequency distally. Associated malignancies were present in a fourth of the patients. Presenting signs and symptoms were vague and related to either obstruction or bleeding. Barium contrast examination and endoscopy for duodenal tumors were the primary diagnostic modalities. Curative treatment was wide resection of bowel and mesentery for jejunal and ileal tumors and pancreaticoduodenectomy for duodenal tumors. Favorable prognosticators included jejunal location, absence of nodal metastases, and a well-differentiated grade. Stage for stage, the prognosis of patients with adenocarcinoma of the small intestine parallels that of patients with adenocarcinoma of the colon. With greater awareness of this tumor, it is possible that earlier detection will lead to improved overall survival.

An evaluation of new methods of expressing aortic aneurysm size: Relationship to rupture

The diameter of aortic aneurysms were standardized to measures of patient size and normal aortic size in an effort to define indexes that might be more predictive of aneurysm rupture than raw aneurysm diameter alone. Normal aortic diameters were measured in 100 patients undergoing abdominal CT scans for other reasons, and an average infrarenal aortic diameter of 2.10 +/- 0.05 cm was observed. Normal aortic diameter was dependent on both age and sex, ranging from 1.71 +/- 0.06 cm in women below age 40 years to 2.85 +/- 0.04 cm in men above age 70 years. Overall, 11 (5.1%) of the ruptures occurred in aneurysms less than 5 cm in diameter, and four (1.9%) occurred in aneurysms less than 4.0 cm in diameter. When the CT scans of 100 patients undergoing elective aneurysm resection were compared with those of 36 patients with ruptured aneurysms, no threshold diameter value accurately discriminated between the two groups. However, standardization of the aneurysm diameter to the transverse diameter of the third lumbar vertebral body as an index of patient body size produced an accurate predictor of rupture when a threshold ratio of 1.0 was used. No aneurysm ruptured below this ratio, but 29% of elective aneurysms were smaller than the vertebral body diameter. Receiver operating characteristic curve analysis confirmed the superiority of the aneurysm to vertebral body diameter ratio as a discriminator of ruptured aneurysms. It appears that aneurysm diameter alone is not sufficiently predictive of rupture to be used as the sole indication for elective resection.