Catheter-Based Reperfusion Treatment of Pulmonary Embolism

Acute pulmonary embolism (PE) is a life-threatening condition with an estimated overall mortality rate of ≈15% at 3 months.² Massive (or high-risk) PE is defined as acute PE with sustained systemic arterial hypotension (usually systolic arterial pressure 90 mm Hg), cardiogenic shock, or the need for cardiopulmonary resuscitation; the in-hospital mortality rate may exceed 50%.³ Submassive (or intermediate-risk) PE is associated with preserved systemic arterial pressure, but with right ventricular dysfunction on echocardiography or with elevated cardiac biomarkers; the in-hospital mortality ranges between 6% and 8%.^4,5 Patients with low-risk PE are hemodynamically stable and have neither right ventricular dysfunction nor elevated cardiac biomarkers; these patients usually have excellent short-term prognosis once therapeutic levels of anticoagulation are established.⁶

A scientific guideline statement from the American Heart Association⁷ provides detailed recommendations on the management of acute PE, including suggestions on the use of reperfusion therapy, ie, systemic thrombolysis, catheter interventions, and surgical embolectomy (Figure 2).

Thrombolysis with a 2-hour continuous intravenous infusion of 100 mg of recombinant tissue plasminogen activator is approved by the Food and Drug Administration for patients with massive PE and may be considered in patients with submassive acute PE judged to have clinical evidence of adverse prognosis. However, a meta-analysis including 13 randomized clinical trials of fibrinolysis versus heparin treatment alone showed no significant reduction in recurrent PE or death.⁷ In addition, systemic thrombolysis has absolute and relative contraindications.⁷ Absolute contraindications include any prior intracranial hemorrhage, known structural intracranial cerebrovascular disease (eg, arteriovenous malformation), known malignant intracranial neoplasm, ischemic stroke within 3 months, suspected aortic dissection, active bleeding or bleeding diathesis, recent surgery encroaching on the spinal canal or brain, or significant closed-head or facial trauma with radiographic evidence of bony fracture or brain injury. Relative contraindications are age >75 years; current use of anticoagulation therapy; pregnancy; puncture of a noncompressible vessel; traumatic or prolonged cardiopulmonary resuscitation (>10 minutes); internal bleeding (within 2–4 weeks); history of chronic, severe, and poorly controlled hypertension or severe uncontrolled hypertension on presentation; dementia; remote (>3 months) ischemic stroke; and major surgery within 3 weeks. It is therefore not surprising that up to two thirds of the patients with massive PE do not receive systemic thrombolysis.⁵ Furthermore, even in selected patients without absolute contraindications to thrombolysis, up to 20% of major hemorrhages and 3% to 5% of intracranial bleeding complications have been reported.^2,8

Surgical embolectomy requires cardiopulmonary bypass for extracting centrally obstructing pulmonary emboli and is an alternative reperfusion treatment option if absolute contraindications to thrombolysis are present and if performed in an experienced center. According to a meta-analysis on case studies of surgical embolectomy, the pooled mortality rate of 19% from the last decade has substantially improved compared with the pooled mortality rate of 35% before 1990. This observation may likely be attributed to improved surgical techniques and to a change in patient selection.⁹

Percutaneous catheter-based interventions are appropriate if systemic full-dose thrombolysis is contraindicated or urgent recanalization of PE is warranted, and if performed in an experienced center. The goal of the catheter intervention is the removal of the obstructing thrombi from the main or lower lobe pulmonary arteries, to facilitate right ventricular recovery, and to improve symptoms and survival.^7,10 Since the first description of the Greenfield embolectomy device in 1971,¹¹ several catheter-based techniques have been introduced.¹⁰

For patients with absolute contraindications to thrombolysis, contemporary catheter intervention techniques can be separated into 4 categories: (1) thrombus fragmentation, (2) rheolytic thrombectomy, (3) suction thrombectomy, and (4) rotational thrombectomy (Table 1). For patients without absolute contraindications to thrombolysis, 2 approaches are being used: (1) conventional catheter-directed thrombolysis (CDT) and (2) pharmacomechanical thrombolysis (PMT).

PMT is defined as the combination of CDT with a mechanical catheter intervention technique. The combination of thrombus fragmentation or aspiration with CDT may be particularly useful for patients with hemodynamic instability. Another PMT approach is the Power Pulse spray technique for intraclot delivery of low doses of thrombolytic agents, facilitating rheolytic thrombectomy with the AngioJet device. Ultrasound-enhanced thrombolysis may be considered as PMT and is a combination of CDT with a sophisticated catheter system that uses high-frequency, low-power ultrasound. Ultrasound itself cannot dissolve thrombus, but enhances fibrinolysis by causing reversible disaggregation of uncrosslinked fibrin fibers, thereby increasing thrombus permeability for the thrombolytic drug. In addition, ultrasound pressure waves augment the penetration of thrombolytic drug.^22–24

Catheter interventions have not been compared in a randomized trial with treatment with systemic thrombolysis or with anticoagulation alone, and current evidence is based on single-center case series. An extensive systematic review on mechanical catheter interventions with or without CDT included 6 prospective and 29 retrospective studies with a total of 594 PE patients who underwent a mechanical catheter intervention with currently available low-profile devices (≤10F).¹⁹ The pooled clinical success rate, defined as stabilization of hemodynamic parameters, resolution of hypoxia, and survival of massive PE, was 86%. The effect of the mechanical catheter intervention on the clinical success rate is difficult to assess because 67% of patients received local thrombolysis during the procedure. The success rate was higher in studies in which at least 80% of patients received additional CDT compared with studies with less frequent use of CDT (91% versus 83%). Overall, minor and major procedural complications occurred in 8% and 2%, respectively. A total of 5 procedural-related deaths were reported, 1 from bradyarrhythmia, 1 from widespread distal embolization, 1 associated with cerebrovascular hemorrhage, and 2 with unknown cause.

Another systematic review also included studies of older techniques, such as suction embolectomy with the Greenfield device, and reported an overall clinical success rate of 95% with and 81% without additional use of CDT.²¹

Although a mechanical catheter intervention without thrombolysis is likely not as effective as an intervention with CDT, immediate improvement in hemodynamic measurements has been reported with thrombus fragmentation²⁵ and with a combination of thrombus fragmentation with rotational thrombectomy.¹⁵ It also remains unclear whether PMT is superior to CDT. In a nonrandomized retrospective study of 33 patients, ultrasound-enhanced thrombolysis resulted in an improved treatment outcome, reduced duration of the thrombolysis infusion, and reduced treatment-related hemorrhagic complications compared with CDT alone.²⁶ In a retrospective analysis of 24 patients with massive and submassive PE, ultrasound-enhanced thrombolysis rapidly reduced right ventricular enlargement by chest computed tomography.¹ A randomized clinical trial called ULTIMA is currently recruiting patients in Switzerland and Germany with submassive PE to test whether ultrasound-enhanced, low-dose thrombolysis is superior to anticoagulation alone in improving right ventricular enlargement (NCT01166997).

Publication bias likely caused an underreporting of serious complications that may occur with catheter interventions in acute PE; these include periprocedural hemodynamic deterioration, distal embolization, pulmonary artery perforation, systemic bleeding complications, lung hemorrhage, pericardial tamponade, transient heart block or bradycardia, contrast-induced nephropathy, and access-related complications, including hematoma, pseudoaneurysm, or arteriovenous fistula.

Patients undergoing invasive pulmonary angiography and catheter intervention require continuous hemodynamic and electrocardiographic monitoring. Duplex ultrasonography of the common femoral vein is useful to rule out suspected concomitant iliofemoral DVT.

In our opinion, it is important to obtain complete right heart hemodynamic measurements before and after completion of the procedure for monitoring the treatment effect (Table 2). The amount of iodine contrast agent should be kept as low as possible and depends mainly on the hemodynamic status and the size of the selected vessel. Despite lower contrast agent requirements with digital subtraction angiography, this technique is not routinely recommended, because most patients with massive PE cannot hold their breath. Nonselective angiography with large (>30 mL) amounts of contrast agent via power injector should be avoided due to the risk of worsening right ventricular failure. To minimize the risk of pulmonary artery perforation, the main and lower lobe pulmonary arteries should be considered for treatment, and segmental branches with a diameter of <6 mm should not be approached.²⁷

In addition to treatment with dose-adjusted unfractionated heparin, a catheter intervention was selected in both cases. For the first case, bilateral ultrasound-enhanced thrombolysis was immediately initiated with the administration of 26 mg t-PA over 15 hours (3-mg bolus per device, 10-mg continuous infusion per device over 15 hours) (Figure 3). At completion of the infusion, the patient had improved his hemodynamic measurements: systolic blood pressure 115 mm Hg, heart rate 84 beats per minute, and oxygen saturation 90% on 3 L of supplemental oxygen. Follow-up angiography showed complete reperfusion of the left pulmonary artery and residual nonobstructive thrombus in both pulmonary arteries. The mean pulmonary artery pressure decreased from 39 to 27 mm Hg, and cardiac output increased to from 3.1 to 4.7 L/min. For the second case, it was decided to select a catheter intervention without thrombolysis by using a combined mechanical approach with bilateral pigtail fragmentation and rheolytic thrombectomy. Two thrombectomy runs were performed in both main pulmonary arteries with the AngioJet 6F device. During thrombectomy, the device was advanced at a speed of approximately 5 mm per second. Each thrombectomy run consisted of 2 parts: 1) thrombectomy during 15 seconds from proximal to distal and 2) thrombectomy during 15 seconds from distal to proximal. At completion of the procedure, there was residual thrombus and modest improvement in flow in both pulmonary arteries. The patient remained hypotensive, with a systolic arterial pressure of 85 mm Hg and heart rate of 115 beats per minute. Mean pulmonary artery pressure remained elevated at 35 mm Hg (baseline 37 mm Hg), and cardiac output remained low at 3.2 L/min (baseline 3.0 L/min). Over the next 24 hours, the patient slowly improved, and the norepinephrine infusion was successfully weaned. Both patients were discharged alive on anticoagulant therapy.

Dr Kucher reports being a consultant for EKOS Corp and MEDRAD and having received honoraria from Sanofi-aventis, Boehringer Ingelheim, and Bayer. Dr Engelberger reports no conflict.