Thrombolytic therapy of acute pulmonary embolism: current status and future potential.

Recombinant human tissue-type plasminogen activator (rt-PA), a relatively clot-specific fibrinolytic agent, represents a novel and promising approach to thrombolytic therapy of pulmonary embolism. Therefore, the efficacy and safety of peripheral intravenous rt-PA therapy were assessed in 47 patients with angiographically documented pulmonary embolism. The drug regimen was 50 mg over 2 hours followed by repeat angiography and, if necessary, an additional 40 mg over 4 hours. By 6 hours, 44 of the 47 patients had angiographic evidence of clot lysis that was slight (n = 5), moderate (n = 12) or marked (n = 27). Among the 34 patients with pulmonary hypertension before treatment (mean pulmonary artery pressure exceeding 17 mm Hg), the pressure decreased from 43/17 (mean 27) to 31/13 (mean 19) mm Hg (p less than 0.0001). Fibrinogen decreased 33% from baseline at 2 hours and 42% from baseline at 6 hours. There were two major complications that required surgical control of bleeding: hemorrhage from a pelvic tumor and mediastinal tamponade in a patient 8 days after coronary artery bypass surgery. The initial results demonstrate that, among selected patients, peripheral intravenous rt-PA can rapidly and, for the most part, safely lyse pulmonary embolism within 6 hours.

Renal vasomotion in essential hypertension: influence of vasodilators.

To assess factors responsible for phasic behavior of renal blood flow in essential hypertension, we applied an analytic method based on the estimation of power spectral density to xenon transit through the kidney and examined the renal vasodilator response to a range of agents in 53 normal subjects and 53 patients with essential hypertension. The renal vasodilator response to the calcium channel blocking agent diltiazem, but not the response to alpha-adrenergic blockade (phentolamine) or angiotensin converting enzyme inhibition (teprotide or captopril), was associated with a significant reduction in the amplitude of renal vasomotion. Acetylcholine, a vasodilator that acts through the release of a vasorelaxant factor or factors from endothelium, induced an unanticipated increase in renal vasomotion. These observations further dissociate factors responsible for basal renal vascular tone and periodic changes in renal vascular tone and raise the possibility that abnormalities in the flux of calcium into renal arterioles contribute to increased renal vasomotion in essential hypertension.

Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis.

PURPOSE: To compare the efficacy and safety of recombinant human tissue-type plasminogen activator (rt-PA, supplied as Activase) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis (DVT) of the leg. PATIENTS AND METHODS: Sixty-four patients underwent 65 randomizations to rt-PA alone (n = 36), rt-PA plus heparin (n = 17), or heparin alone (n = 12) in a prospective, multicenter, randomized, open-label trial, with efficacy assessed by a radiology panel unaware of treatment assignment. Patients randomly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein, with a maximum dose of 150 mg. All patients then received heparin and warfarin for the remainder of the hospitalization. Follow-up venography was performed 24 to 36 hours after initiation of therapy. RESULTS: Complete or more than 50% lysis occurred in 10 (28%) patients treated with rt-PA, five (29%) patients with rt-PA plus heparin, and no patient treated with heparin. No lysis occurred in 16 (44%) patients treated with rt-PA plus heparin, and 10 (83%) patients who received heparin alone (p = 0.04). There was one major complication, a nonfatal intracranial hemorrhage in a patient who received rt-PA alone. At 7 to 10 days after initiation of treatment, the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients, including those assigned to receive heparin alone. CONCLUSION: (1) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone; (2) the addition of heparin to rt-PA does not improve the lysis rate; (3) DVT treated with heparin is commonly associated with a rise in the transaminase level; (4) heparin does not increase the risk of bleeding from rt-PA therapy; and (5) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT.

Influence of variability of interpretation of contrast venography for screening of postoperative deep venous thrombosis on the results of a thromboprophylactic study.

To assess interobserver variability of venography for screening for postoperative deep venous thrombosis (DVT), we used 185 bilateral ascending contrast venograms (366 lower limbs) which were performed using the long-leg film technique, in the frame of a trial of the efficacy of two low-molecular-weight-heparin fractions (initial evaluation). These venograms were submitted in a multicenter setting to three further readers who performed a serial scoring as DVT, no DVT or non-evaluable. DVTs were diagnosed in 78, 55 and 59/366 limbs (initial evaluation: 58). The proximal locations of DVTs were 16, 9 and 16 (initial evaluation: 15) and the non evaluable limbs 3, 5 and 18 (initial evaluation: 0). Apparent pairwise agreement between the three readers ranged from 87 to 90% (true coefficient of agreement Kappa 0.63-0.70). It ranged from 89 to 93% (Kappa 0.63-0.74) for the comparison between the readers and the initial evaluation. This considerable degree of disagreement among experienced readers should be taken into account in calculating sample sizes in prospective thromboprophylactic studies. Indeed, one of the two prophylactic regimens proved to be significantly (p = 0.012, p = 0.031, p = 0.049) or non-significantly (p = 0.073) superior to the other one depending upon the reading of venograms.

Efficacy and safety of repeated boluses of urokinase in the treatment of deep venous thrombosis.

The only Food and Drug Administration-approved thrombolytic regimen for treatment of deep venous thrombosis (DVT) is a 24- to 72-hour continuous infusion of intravenous streptokinase. This approach to DVT thrombolysis is not entirely satisfactory because of the bleeding complications that may accompany this therapy. In the current study, we treated 27 patients with DVT with a novel dosing regimen of urokinase: 1,000,000 U administered as a 10-minute bolus, with a total of 3 boluses given over approximately 24 hours. Patients were given heparin overnight between bolus urokinase doses. Efficacy was assessed by comparing baseline and prehospital discharge vascular imaging studies, which constituted either venous ultrasound or contrast venography. A vascular-imaging panel of physicians, unaware of the sequence of paired studies, found that 14 patients (52%) had clot lysis (6 slight, 6 moderate and 2 marked), 9 (33%) had no change, and 4 (15%) had more extensive thrombosis after treatment (1 slight, 2 moderate and 1 marked). There were no bleeding complications. At 48 hours after starting urokinase, mean plasma fibrinogen levels had decreased 61% from baseline, and the mean bleeding time had increased 28% from baseline (but remained within the normal range). Because of the promising efficacy and safety that were found in this case series, it is concluded that further testing of bolus urokinase is warranted against anticoagulation alone.

How to maximize the safety of coronary and pulmonary angiography in patients receiving thrombolytic therapy.

Patients who receive thrombolytic therapy in close temporal relationship to undergoing coronary or pulmonary angiography are at high risk of developing hemorrhagic complications, particularly at the vascular access site. A single-wall percutaneous puncture technique, use of a sheath for vascular access, use of a pigtail catheter for pulmonary angiography, avoidance of a temporary pacing catheter, and shortening the duration of thrombolytic therapy will decrease these complications. However, to maximize the safety of thrombolytic therapy, invasive vascular procedures should be avoided whenever possible.

Frequency of pulmonary embolism in patients with low-probability lung scan and negative lower extremity venous ultrasound.

STUDY OBJECTIVES: To define the prevalence of pulmonary embolism (PE) in patients who are undergoing pulmonary arteriography because of a high clinical suspicion for PE but who have had a low-probability lung scan and a negative lower extremity venous ultrasound examination. DESIGN: A retrospective review of the medical records of 365 consecutive patients who underwent pulmonary arteriograms for suspected PE was undertaken. RESULTS: Of the 365 pulmonary arteriograms, 62 were performed in patients with suspected PEs despite a low-probability lung scan and a negative lower extremity venous ultrasound examination. In the latter group, five patients (8%; 95% confidence interval, 2.7% to 18%) had PEs revealed on the arteriogram. CONCLUSIONS: In patients whose presentation provokes a high clinical suspicion for PE despite having had a low-probability lung scan, a negative lower extremity venous ultrasound examination is insufficient to preclude proceeding to pulmonary angiography.

Evaluation of optimized biplane pulmonary cineangiography.

Biplane pulmonary cineangiograms utilizing a short cine pulse width and automatic brightness control were performed in 47 patients during normal respiration. The diagnostic quality of the arteriograms was categorized as good in 33 patients, fair in 12 patients, and poor in two patients. Of the 18 patients in whom pulmonary emboli were identified, cineangiography displayed certain diagnostic features to advantage, including motion of emboli in ten and respiratory scissoring of vessels overcoming vascular superimposition in three. Optimized pulmonary cineangiography is an acceptable alternative to serial film pulmonary angiography for the diagnosis of pulmonary embolism.

Preoperative angiographic uterine artery embolization in the management of cervical pregnancy.

The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of extensive hemorrhage during attempted evacuation. In some cases, hysterectomy has been the necessary treatment to control bleeding. We report two cases of cervical pregnancy detected by ultrasound. Before pregnancy termination, the uterine arteries were successfully embolized using angiographic techniques. As a result, surgical evacuation was performed with minimal hemorrhage; hysterectomy was not required and the patients' potential fertility was retained.

Percutaneous transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) has revolutionized the treatment of patients with coronary disease. As many as 25 per cent of those requiring myocardial revascularization can now undergo PTCA instead of bypass surgery. This article reviews PTCA techniques, clinical results, case selection, complications, recent advances in equipment design, restenosis rate, use in acute myocardial infarction, and PTCA of coronary bypass grafts.

Patency results of percutaneous and surgical revascularization for femoropopliteal arterial disease.

To estimate the patency results of percutaneous transluminal angioplasty and bypass surgery in the treatment of femoropopliteal arterial disease, a Medlars search of the English-language medical literature was performed. Inclusion required that studies 1) report original data, 2) report patency with a life table or Kaplan-Meier analysis with the number at risk or standard errors, 3) define patency as hemodynamic improvement, 4) report the distribution of covariates, and 5) not duplicate other published material. Using a method based on the proportional-hazards model and the actuarial life-table approach, the results were adjusted for differences in case-mix of the study populations and patency was predicted for subgroups at various levels of risk for failure. The unadjusted pooled life tables yielded five-year patencies of 45% (+/- 2%) for angioplasty, 73% (+/- 2%) for bypass surgery using a vein graft, and 49% (+/- 3%) for bypass surgery using a polytetrafluoroethylene graft. Adjusted five-year primary patencies after angioplasty varied from 12% to 68%, the best results being for patients with claudication and stenotic lesions. Adjusted five-year primary patencies after surgery varied from 33% to 80%, the best results being for saphenous vein bypass performed for claudication. The authors conclude that pooling life-table data without adjustment for covariates can be misleading. Indication, lesion type, vein graft availability, and site of the distal graft anastomosis need to be considered in predicting patency results of revascularization for femoropopliteal arterial disease.

Hysterosalpingography and fallopian tube cannulation: use of a double-balloon introducing catheter.

A double-balloon introducing catheter for cervical cannulation is described. The catheter can be used for hysterosalpingography and allows coaxial passage of a 5-F curved catheter to selectively catheterize the fallopian tubes. The device has been used successfully in eight patients and may offer several advantages over other currently available equipment.

Drug variables in thrombolytic therapy.

Fibrinolytic therapy has become an accepted treatment modality for recent peripheral arterial and bypass graft occlusions and, in some cases, for chronic arterial occlusions. Streptokinase, urokinase, and tissue plasminogen activator have all been used for intraarterial infusion with varying protocols and results. This review focuses on dosing variables and clinical results for the various thrombolytic agents in peripheral arterial and bypass graft occlusions. Also discussed are new thrombolytic agents and the effects of concomitant use of other drugs as part of the treatment regimen.

Typhlitis: a cause of gastrointestinal hemorrhage in children.

Three children with typhilitis complicating acute leukemia and presenting with severe intestinal hemorrhage are described. The arteriographic findings were hypervascularity of the cecum with intense mucosal staining, opacification of superficial ulcers, and arteriovenous shunting into dilated mesenteric veins. The three children were managed successfully with medical, surgical, and embolic therapies, respectively.

Angiography in gastrointestinal bleeding in children.

Twenty-seven children aged 1 day to 16 years studied arteriographically for acute or chronic gastrointestinal bleeding were reviewed. Children with known esophageal varices and portal hypertension were excluded. Final diagnoses were made in 25 patients by means of surgery, endoscopy, biopsy, laboratory data, and clinical follow-up. Of these 25 cases, arteriography gave a correct diagnosis in 64% and was falsely negative in 36%. In acute gastrointestinal bleeding, arteriographic diagnosis was correct in 71% and falsely negative in 29%. In chronic or recurrent gastrointestinal bleeding, arteriographic diagnosis was correct in 55% and falsely negative in 45%. The common causes of bleeding in this study were gastric and duodenal ulcers, gastritis, vascular malformations, and typhlitis. Transcatheter therapy was attempted in six acute bleeders, with success in three (50%).

Accuracy of color Doppler flow mapping for evaluation of the severity of femoropopliteal arterial disease: a prospective study.

The usefulness of color Doppler flow mapping for estimating the severity of femoropopliteal lesions was compared with that of angiography in 35 patients (70 extremities). Sonography depicted significant (greater than 40% luminal narrowing) arterial lesions in 45 of 47 lower extremities in which such lesions were present (sensitivity, 0.96 [95% confidence limits; 0.86, 0.99]). The absence of significant segmental stenosis or occlusion was confirmed in 15 of the 23 normal extremities (specificity, 0.65 [0.45, 0.81]). Occlusions amenable to bypass surgery were correctly predicted in 25 of 26 (sensitivity, 0.96 [0.81, 0.99]) and were excluded in 41 of 44 extremities (specificity, 0.93 [0.82, 0.98]). Lesions amenable to angioplasty were detected in 16 of 21 instances, with overestimation of severity in three lesions that were judged suitable for bypass surgery; two lesions were missed. Preangiographic screening with color Doppler flow mapping is an accurate method for predicting the presence of femoropopliteal artery occlusions amenable to bypass surgery. It is also a sensitive method for predicting the presence of peripheral arterial disease.

Percutaneous venous interventions.

Percutaneous procedures by interventional radiologists are becoming an increasingly frequent part of the overall care of patients with complex venous thrombotic diseases. Inferior vena caval filters are used in the setting of failed or contraindicated anticoagulation. Catheter-directed thrombolysis is considered for patients with extensive iliofemoral deep venous thrombosis. Venous angioplasty is often indicated for patients with dialysis shunt venous stenoses, upper extremity venous stenoses and for stenoses within venous bypass grafts. Venous stenting is often employed following angioplasty to ensure long-term procedural success. Finally, suction and mechanical thrombectomy and embolectomy are relatively new procedures that are available to optimize patient management.

Treatment of fibromuscular dysplasia and renal artery aneurysm with use of a stent-graft.

A Jostent stent-graft was placed in a renal artery with a focal stenosis and an associated aneurysm in a young patient with fibromuscular dysplasia. Arteriographic follow-up at 16 months showed that the stent-graft remained patent and the aneurysm was excluded.

Caudal-posteroanterior view in coronary arteriography.

Posteroanterior (PA) and caudally angulated PA views were obtained in 20 patients undergoing routine coronary arteriography. Although the left main coronary artery (LMCA) was seen well on both views in all patients, the PA-caudal view improved depiction of the LMCA bifurcation in 15 (75%). In addition, the PA-caudal view markedly improved depiction of the circumflex artery, affording optimal depiction of this artery and its branches in 78%-89% of patients. Neither the PA nor the PA-caudal view allowed adequate depiction of the left anterior descending artery. Thus, the PA-caudal view should supplant the PA view in routine coronary arteriography.

Short-term response to thrombolytic therapy in deep venous thrombosis: predictive value of venographic appearance.

To determine whether the response to thrombolytic therapy for lower-extremity deep venous thrombosis (DVT) can be predicted from the venographic appearance, 139 thrombosed venous segments were analyzed. Initial and follow-up venograms were obtained in 62 patients randomized to 24-hour infusions of recombinant human-tissue-type plasminogen activator (rTPA) (n = 34), rTPA plus heparin (n = 16), or heparin alone (n = 12). Segmental response to therapy was evaluated by means of blinded review of the paired venograms. The response (50%-100% lysis) to rTPA alone was significantly greater in venous segments involved with nonobstructive thrombi than in those with obstructive thrombi (12 of 23 vs five of 51; P less than .005). Results were similar for the combination of rTPA and heparin (five of six vs six of 30, P less than .01). No significant difference was seen in the response of either obstructive or nonobstructive thrombus to heparin alone. Thrombotic tails responded substantially (greater than 50% decrease in size) to rTPA with or without heparin in 22 of 24 patients. The venographic appearance of DVT appears to help in predicting the therapeutic response to thrombolytic therapy.