By Samuel Nadler, MD, PhD
Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle, WA
Dr. Nadler reports no relationships relevant to this field of study.
SYNOPSIS: Catheter-directed thrombolysis safely reduced mean pulmonary artery pressures and right ventricular strain in massive and submassive PE.
SOURCE: Kuo WT, et al. Pulmonary embolism response to fragmentation, embolectomy, and catheter thrombolysis (PERFECT): Initial results from a prospective multicenter registry. Chest 2015 April 9 [Epub ahead of print].
Pulmonary embolism (PE) that is associated with hemodynamic instability and right heart strain carries significant mortality, and in severe cases, can be treated with thrombolysis. However, systemic thrombolysis is associated with major bleeding complications and hemorrhagic stroke, which mitigates its overall benefit. Catheter-directed thrombolysis (CDT) allows thrombolytics to be delivered directly into the thrombus, thereby lowering the required dose and potentially reducing these associated complications, which can result in improved overall outcomes.
The PERFECT study is a prospective registry of 101 patients receiving CDT in six centers in the United States and one in Europe. Patients included in this study had massive (28/101) or submassive (73/101) PEs within the main or lobar pulmonary artery leading to right ventricular strain or hemodynamic instability, were ≥ 18 years of age, had no contraindication to therapeutic anticoagulation, and did not have tumor thrombus. Massive PE was defined as sustained hypotension or the requirement of inotropic support. Submassive PE was defined by RV strain assessed by echocardiography or CT scanning. Tissue plasminogen activator (tPA), or urokinase, was infused into the clot using standard infusion catheters or ultrasound-assisted infusion catheters (USAT). Massive PEs were pre-treated with mechanical thrombolysis or thrombectomy prior to infusion. Clinical success was defined as stabilization of hemodynamic parameters, improvement of pulmonary artery pressure, and survival to hospital discharge. This was accomplished in 85.7% (24/28) and 97.3% (71/73) of patients with massive and submassive PE, respectively. There were six deaths reported, but no major procedure-related complications, major hemorrhages, or hemorrhagic strokes. Minor bleeding occurred in 12.9% (13/101), all of which were self-limiting and did not require blood transfusions. These episodes were due to hematoma formation at the access site (6/13) as well as two episodes of hemoptysis and hematuria, and one episode each of epistaxis, vaginal bleeding, and IV site bleeding.
COMMENTARY
The main purposes of this study were to add to the understanding of the safety and feasibility of CDT and build upon the previously reported ULTIMA and SEATTLE II studies.1,2 This was not a randomized controlled trial of CDT vs systemic thrombolysis. Although this study involved a “real-world population” as the authors note, it was conducted in select centers that already had expertise in this treatment, and therefore, the generalizability of this study is unclear. With that caveat, this study demonstrated efficacy of CDT for reducing mean pulmonary artery pressures and markers of right ventricular strain, similar to previous studies. As there currently seems to be equipoise between systemic thrombolysis and CDT for submassive PE, a well-designed, randomized controlled study should be undertaken to address which treatment modality is best suited for this condition.
This registry sheds light on two other aspects of the management of massive and submassive PE. First, 64.4% (65/101) of patients received inferior venal cava (IVC) filters. It is not clear if these were removable filters and what the indication was for placement. Presumably, there was concern for additional clot burden in the legs. During the infusion of thrombolytics, which averaged greater than 20 hours, no systemic anticoagulation was administered, and this might predispose to extension of lower extremity deep venous thrombosis necessitating IVC filter placement. Second, there seemed to be no benefit to USAT catheters compared with standard infusion catheters. The two systems demonstrated similar reductions in pulmonary artery pressures (-13.76 vs -14.02 mm Hg), average infusion times (23.19 vs 20.76 hours), and average tPA doses (30.27 vs 25.63 mg).
In considering whether CDT is most appropriate for the treatment of submassive PE, some insights can be gained by comparing this registry with the recently published PEITHO trial, a randomized controlled trial of systemic thrombolysis plus heparin vs heparin alone for submassive PE.3 In PEITHO, the 30-day mortality was 2.4% (12/506) vs 3.2% (16/499) in the systemic thrombolytic and heparin-only arms, respectively. In PERFECT, the in-hospital mortality for submassive PE was 2.7% (2/73). Conversely, PEITHO reported major bleeding in 11.5% and 2.4% of patients receiving thrombolytics and heparin vs heparin alone, compared with no reported major bleeding in the much smaller PERFECT study. Thus, this study suggests that CDT is equally effective at treating submassive PE compared with systemic thrombolysis and may lead to fewer complications. However, a randomized controlled trial directly comparing these treatments is needed.
REFERENCES
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Kucher N, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014;129:479-486.
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Piazza G, et al. A prospective, single-arm, multicenter trial of the EkoSonic endovascular system with activase for acute pulmonary embolism (SEATTLE II). American College of Cardiology 63rd Annual Scientific Meeting, Washington, DC, March 28-31,2014.
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Meyer G, Vicaut, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370:1402-1411.
