Endovascular Treatment of Massive and Submassive Pulmonary Embolism Ethan Dobrow, MD,* and Paul Kim, MD† Massive and submassive pulmonary embolism constitutes the high- and intermediaterisk categories of pulmonary embolism. Both are associated with higher rates of mortality and morbidity and may benefit from more aggressive management than from standard anticoagulation alone. Endovascular treatment is a promising treatment modality that may offer added benefit at low additional risk. Tech Vasc Interventional Rad 17:121-126 C 2014 Elsevier Inc. All rights reserved. KEYWORDS pulmonary embolism, thrombolysis, thrombectomy
Introduction Acute pulmonary embolism (PE) is a common lifethreatening illness, with an estimated incidence of 530,000 cases in the United States per year.1 Acute PE can be stratified as high-risk or massive PE, intermediaterisk or submassive PE, and low-risk or nonmassive PE, with nearly 300,000 deaths a year attributable to PE.2 Mortality rates are high when patients present in hemodynamic shock, with reports up to 58%, and usually occur within an hour of presentation.3 Patients who survive are at risk for the development of recurrent PE or chronic thromboembolic pulmonary artery (PA) hypertension.4,5 Most deaths associated with PE are attributable to right ventricular (RV) failure.6 Patients presenting with massive PE demonstrate systemic hypotension (systolic blood pressure less than 90 mm Hg), cardiogenic shock, cardiac arrest, or RV dysfunction. Patients with submassive PE demonstrate echocardiographic and enzymatic evidence of RV dysfunction and myocardial injury but preserved systolic pressures (490 mm Hg). Patients with low-risk PE show no evidence of right-sided heart strain or myocardial injury. It is crucial to appropriately risk stratify these patients so that the treatment can be appropriately administered.
Massive PE In patients with massive PE, rapid escalation of care is imperative. The use of anticoagulation with unfractionated heparin, low-molecular-weight heparin, or fondaparinux has been advised.2,4 Intravenous infusion of the thrombolytic alteplase (IV r-tPA) (Genentech, South San Francisco, CA) at a dose of 100 mg infused over 2 hours has Food and Drug Administration approval for use in massive PE and is recommended for unstable patients with PE.7 However, after appropriate screening many patients have absolute contraindications to IV r-tPA. Even in patients who are carefully screened and without contraindications, the risk of major hemorrhage is 20% and the risk of intracranial hemorrhage is 3%-5%.4 In a large retrospective study reviewing thrombolytic therapy for massive PE, the authors found that over the past decade, only 30% of unstable patients received IV thrombolysis with an inhospital mortality rate of 15%. The remaining 70% of patients had an in-hospital mortality rate of 47%, with a pooled in-hospital mortality rate more than 37%.8 William Kuo et al in a meta-analysis of catheter-directed thrombolysis (CDT) for massive PE demonstrated a nearly 87% improvement in the clinical status. There was a major complication rate of 2.4% with only 1 reported intracranial hemorrhage among 571 patients.9
Submassive PE *Department of Radiology, Maine Medical Center, Portland, ME. †Vascular and Interventional Physicians, Spectrum Medical Group, South Portland, ME. Address reprint requests to Paul Kim, MD, Vascular and Interventional Physicians, Spectrum Medical Group, South Portland, ME. E-mail: [email protected] 1089-2516/13/$ - see front matter & 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.tvir.2014.02.010
Patients presenting with submassive PE, or intermediaterisk PE, often remain normotensive. Despite this more stable presentation, this subset of patients remains at an increased risk for adverse outcomes with mortality rates in the range of 5%-10%.10 Submassive PE is defined as maintenance of systolic blood pressures Z90 mm Hg, 121
E. Dobrow and P. Kim
122 but with echocardiographic or computed tomography evidence of right-sided heart strain as well as laboratory markers of RV strain or ischemia. On imaging with either echocardiography or pulmonary computed tomography angiography, a right-ventricular-to-left-ventricular end-diastolic ratio of Z0.9 has been demonstrated to be an independent predictor of increased mortality. This group remains at an increased risk of developing chronic PE and chronic thromboembolic PA hypertension.10-16
Rationale for CDT Although the IV infusion of r-tPA is Food and Drug Administration approved for the treatment of massive PE, it is estimated that only 30% of patients have been given this treatment over the past decade.8 Many patients have contraindications for systemic thrombolysis, and in such cases, further treatment options include surgical embolectomy, which itself has a pooled mortality rate of 19%,17 or endovascular treatment. Endovascular treatment with modern techniques has shown to be effective and safe in the treatment of massive PE, with a pooled success rate of nearly 86% with a low rate of major complications at 2.4% compared with the 20% rate of major complications from IV r-tPA.4,9 Catheter-directed fragmentation allows rapid maceration of large, central pulmonary emboli, which has the dual effect of increasing pulmonary perfusion and decreasing PA pressures, thereby decreasing RV strain. The most frequent mechanical technique employs clot fragmentation with the rotating pigtail catheter.17-19 Endovascular treatments can be tailored based on the clinical risk of bleeding so that, if able, pharmacologic treatments can be combined with catheter treatments to administer lower overall doses of thrombolytic agent directly into the thrombus as compared with IV thrombolysis. Flow studies have validated the concept that intrathrombus infusion of the thrombolytic agent improves thrombolysis by demonstrating that obstructing pulmonary emboli causes alteration in hemodynamics such that the drug administered upstream is prevented from making contact with its intended target, with rapid washout of the drug through nonobstructed pulmonary arteries.20 The intrathrombus infusion can be delivered using a standard infusion catheter or in combination with high-frequency, low-power ultrasound waves with the EKOS system. This technology has the added benefit of causing the fibrin strands to thin and loosen, thus allowing greater exposure of plasminogen receptor sites, as well as increasing thrombus permeability, which can result in greater penetration of the drug.21 Data also suggest that more aggressive treatment of submassive PE with a thrombolytic may result in lower short-term morbidity and likelihood of clinical deterioration during the hospital stay.22 The ULTIMA trial and a recent retrospective study by Kennedy et al have shown that pharmacomechanical thrombolysis with the EKOS ultrasound-accelerated infusion catheter is both safe and effective at reversing RV dysfunction at 24 hours and at
90 days, without the associated risks of full-dose systemic thrombolysis.21,23
Endovascular Treatment of Submassive and Massive PE Submassive PE Given that these patients have overall low in-hospital mortality, it is important to document that they have signs of a PE that are significant enough to warrant endovascular treatment. The trigger for using an endovascular approach for treating these patients is evidence of right-sided heart strain based on either echocardiography or computed tomography angiography imaging. If they have signs of right-sided heart strain and PE and are willing to undergo endovascular treatment, we plan for CDT. Because most of these patients are hemodynamically stable, we treat these procedures as urgent but not emergent (ie, start treatment within 24 hours of consultation). We perform these procedures under moderate sedation using IV fentanyl and midazolam. Upon obtaining bilateral common femoral vein access, we often place a retrievable inferior vena cava (IVC) filter in the infrarenal IVC in patients who have a deep venous thrombosis. Our reasoning for placing a filter is that these patients have a significant-enough burden of thrombus, causing rightsided heart dysfunction for which additional protection in the acute phase is reasonable. An alternative singleaccess option includes using a 12-F dual-lumen or 14-F triple-lumen sheath (St. Jude). We then use a variety of pulmonary catheters (APC, Grolman, Cook Medical, Bloomington, IN) to select the main PA. On obtaining PA pressure measurements, we select the right and left pulmonary arteries in sequential fashion. Because the PA pressures are high enough to preclude the use of a power injection, hand injections of 15 mL of iodinated contrast (Omnipaque 350, GE Healthcare) are administered at a high frame rate (6-7 frames per second), as these patients are sometimes unable to perform an adequate breath hold. After placement of a stiff-exchange length wire, an 8-F, 65-cm sheath (Destination sheath, Terumo, Somerset, NJ) is advanced either to the main PA or into the right or left PA. Using an angled catheter and glide wire, the most involved branch or segment of each PA is selected. The catheter is then exchanged for a 12-cm infusion-length catheter for ultrasound-accelerated thrombolysis (BTGEKOS Corporation, Bothell, WA). In an identical fashion, the same steps are performed for selecting the thrombosed segments of the contralateral PA, and a second infusion catheter is placed. Alteplase (Genentech, San Francisco, CA) infusion is started at 0.5 mg/h on each side for a total dose of 1 mg/h (Fig. 1). Systemic unfractionated heparin is administered during thrombolysis to maintain a partial thromboplastin time of 50-65 seconds. These patients are monitored overnight in an intensive care unit or in a step-
Endovascular treatment of massive and submassive pulmonary embolism
123
Figure 1 A 38-year-old man after undergoing urologic surgery 6 hours prior presents with a massive PE. (A) Right pulmonary angiogram demonstrates upper lobe thrombus. (B) A 6-mm balloon angioplasty performed with mildly improved perfusion. (C) Rheolytic thrombectomy performed with AngioJet (arrow). (D) Resolution of thrombus in affected pulmonary artery.
down unit that is trained in the care of patients undergoing thrombolysis. After approximately 24 hours of infusion, the patient is brought back to the procedure room. Changes in oxygen requirement, patient’s symptoms, and vital signs are documented. After removing the EKOS catheters over a wire, PA pressures are remeasured through the sheaths. Repeat pulmonary angiograms are performed. The interventionalist then determines if thrombolysis should be terminated. If the PA pressures remain significantly elevated, we may elect to continue infusion or reposition the catheter into another thrombosed segment. The maximal duration of thrombolysis in our experience has been 48 hours. We obtain a repeat echocardiogram 24 hours after completion of thrombolysis to document the
improvement in RV diameter and function. The patients are transitioned to oral anticoagulation. We routinely use low-molecular-weight heparin and warfarin for a minimum duration of 6 months. A follow-up of these patients is conducted in 3 months at our clinic to assess their clinical status and also to evaluate them for potential IVC filter retrieval at that time.
Massive PE At our institution, patients with suspected massive PE are quickly evaluated for contraindications to systemic thrombolysis. If they are not excluded, they are administered a bolus of tenecteplase IV (0.5 mg/kg with a maximum dose of 50 mg) (Genentech, San Francisco, CA). Although the application of tenecteplase for PE at this time is off label, it
124
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Figure 2 A 66-year-old woman with a submassive PE. (A and B) Bilateral angiograms demonstrate significant clot burden and PA systolic pressure of 58 mm Hg. (C) Placement of bilateral EKOS catheters into right upper and left lower lobes. (D and E) Twenty-four hours later, improvement in perfusion was seen with decrease in main PA pressure to 26 mm Hg.
Endovascular treatment of massive and submassive pulmonary embolism may be a promising alternative to alteplase as it has the benefit of a more rapid delivery than systemic alteplase and has a greater specificity for fibrin. If the patients remain hypotensive or are excluded from systemic thrombolysis, interventional radiology is consulted for emergent thrombectomy. Because of the potential rapid and escalating mortality associated with massive PE, we bring the patient to the angiography suite immediately. The initial setup and steps are similar to our approach to submassive PE with an IVC filter placed followed by catheterization of the PAs with pressure measurements and hand injection angiograms. However, the end point is different, in that our primary goal is to debulk the volume of thrombus proximally so as to allow for some degree of pulmonary venous return to the left side of the heart to allow for systemic perfusion. Therefore, we begin with mechanical thrombectomy. On selection of the thrombosed pulmonary arteries, mechanical fragmentation is attempted with either a pigtail catheter or a balloon maceration. A balloon is undersized relative to the PA to reduce the risk of rupture. Typically a balloon with a diameter of 6-8 mm is used for segmental branches and a balloon with a diameter of 8-12 mm is used for right and left main pulmonary arteries (Fig. 2). Aspiration through the guide sheath is also performed intermittently to remove any mobile or liquefied thrombus. Although controversial, rheolytic thrombectomy with the Solent Omni AngioJet catheter (MedRad, Minneapolis, MN) is employed on occasions when the methods described earlier are not sufficient. We use short (1-2 second) pulses with close attention paid to the electrocardiogram tracings to watch for bradycardia or asystole (Fig. 2). Epinephrine and atropine should be readily available to intervene if necessary. In our experience, no patients have suffered from sustained bradycardia or had an adverse cardiac event secondary to AngioJet thrombectomy utilization in the pulmonary arteries. We have used the AngioJet Solent and AVX catheters to perform thrombectomy in both central and segmental pulmonary arteries. Perforations of vessels beyond the central pulmonary arteries have been reported, and, therefore, extreme care must be taken when treating these vessels. We commonly use boluses of alteplase during thrombectomy procedures. Despite the fact that some patients were excluded from systemic thrombolysis (usually secondary to recent surgery or trauma), we use boluses of alteplase weighing 8-12 mg to a maximum of 20 mg during the procedure. In our experience, no patient has had a significant hemorrhage (requiring transfusion or intracranial hemorrhage) despite using these boluses in seemingly high-risk patients for bleeding. The primary end point is improvement in systemic blood pressure and decrease in PA pressure. If there remains a significant clot burden despite pharmacomechanical attempts, we leave an EKOS infusion catheter for continued thrombolysis at 0.5 mg/h per lung. At this point, the algorithm is similar to that for the patients with submassive PE and they are brought back at 24 hours for repeat PA pressure measurements and angiograms.
125
If the patient with massive PE survives until discharge, we set up an appointment with him or her at 6 weeks postdischarge for clinical follow-up and discussion of potential IVC filter retrieval.
Alternative Thrombectomy Devices The Aspirex catheter (Straub Medical, Wangs, Switzerland) is an over-the-wire (035 in) thrombectomy device indicated for use in the peripheral circulation that uses high-speed rotation and fragmentation aspiration to remove thrombus. Although its Instructions for Use warns against the use of this device in the pulmonary circulation, there are case reports that show some promise in treating PE.24 The Helix Thrombectomy Device (ev3/Covidien) is a 7-F device indicated for removal of clot from dialysis arteriovenous fistula and grafts, which directs a highpressure impeller outflow to the vessel wall with ongoing active aspiration. Mechanical thrombectomy devices such as the Trerotola device (Arrow International) or Cleaner (Argon Medical, Plano, TX) are also approved for thrombectomy of clotted dialysis arteriovenous fistulae and grafts and use direct mechanical disruption of the thrombus for maceration. These devices do not run over the wire, and care must be taken to avoid dissection, perforation, and arrhythmias. AngioVac (Angiodynamics, Latham, NY) is a filtering system used as an adjunct to extracorporeal bypass. It is a 22-F catheter with a balloon-activated distal tip shaped like a funnel. During bypass, active aspiration of the venous flow extends through the filtering system that eliminates all debris from the circulation before returning blood flow to the patient. A perfusionist is required to assist with the bypass portion of the procedure. Although only case reports exist at this time, it appears to be a rapid endovascular method to remove large volumes of thrombus from large veins and the pulmonary arteries.
Conclusion Endovascular therapy has growing evidence for its utilization as part of the treatment algorithm for submassive and massive PE. There are a variety of techniques available for removing or reducing thrombus within the pulmonary circulation. Catheter-based techniques appear to be successful and safe in treating both massive and submassive PE.
References 1. Heit JA, Cohen AT, Anderson FA: Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the U.S. Blood 106:267a, 2005 2. Tapson VF: Acute pulmonary embolism. N Engl J Med 358: 1037-1052, 2008 3. Wood KE: Major pulmonary embolism: Review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest 121:877-905, 2002
126 4. Goldhaber SZ, Visani L, De Rosa M: Acute pulmonary embolism: Clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 353:1386-1389, 1999 5. Piazza G, Goldhaber SZ: Acute pulmonary embolism, part II: Treatment and prophylaxis. Circulation 114:e42-e47, 2006 6. Piazza G, Goldhaber SZ: The acutely decompensated right ventricle: Pathways for diagnosis and management. Chest 128:1836-1852, 2005 7. Kearon C, Kahn KR, Agnelli G, et al: Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 133:454S-545S 8. Stein PD, Matta F: Thrombolytic therapy in unstable patients with acute pulmonary embolism: Saves lives but underused. Am J Med 125:465-470, 2012 9. Kuo WT, Gould MK, Louie JD, et al: Catheter-directed therapy for the treatment of massive pulmonary embolism: Systematic review and meta-analysis of modern techniques. J Vasc Interv Radiol 20:1431-1440, 2009 10. Fremont B, Pacouret G, Jacobi D, et al: Prognostic value of echocardiographic right/left ventricular end-diastolic diameter ratio in patients with acute pulmonary embolism: Results from a monocenter registry of 1416 patients. Chest 133:358-362, 2008 11. Quiroz R, Kucher N, Schoepf UJ, et al: Right ventricular enlargement on chest computed tomography: Prognostic role in acute pulmonary embolism. Circulation 109:2401-2404, 2004 12. Schoepf UJ, Kucher N, Kipfmueller F, et al: Right ventricular enlargement on chest computed tomography: A predictor of early death in acute pulmonary embolism. Circulation 110:3276-3280, 2004 13. Kline JA, Steuerwald MT, Marchick MR, et al: Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: Frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 136:1202-1210, 2009
E. Dobrow and P. Kim 14. van der Meer RW, Pattynama PM, van Strijen MJ, et al: Right ventricular dysfunction and pulmonary obstruction index at helical CT: Prediction of clinical outcome during 3-month follow-up in patients with acute pulmonary embolism. Radiology 235:798-803, 2005 15. Klok FA, Zondag W, van Kralingen KW, et al: Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events. Am J Respir Crit Care Med 181:501-506, 2010 16. Jimenez D, Uresandi F, Otero R, et al: Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: Systematic review and metaanalysis. Chest 136:974-982, 2009 17. Engelberger RP, Kucher N: Catheter-based reperfusion treatment of pulmonary embolism. Circulation 124:2139-2144, 2011 18. Schmitz-Rode T, Janssens U, Duda SH, et al: Massive pulmonary embolism: Percutaneous emergency treatment by pigtail rotation catheter. J Am Coll Cardiol 36:375-380, 2000 19. Kuo WT: Endovascular therapy for acute pulmonary embolism. J Vasc Interv Radiol 23:167-179, 2012 20. Schmitz-Rode T, Kilbinger M, Günther RW: Simulated flow pattern in massive pulmonary embolism: Significance for selective intrapulmonary thrombolysis. Cardiovasc Intervent Radiol 21:199-204, 1998 21. Kennedy RJ, Kenney HH, Dunfee BL: Thrombus resolution and hemodynamic recovery using ultrasound-accelerated thrombolysis in acute pulmonary embolism. J Vasc Interv Radiol 24:841-848, 2013 22. Konstantinides S, Geibel A, Heusel G, et al: Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 347:1143-1150, 2002 23. Kucher N: The ULTIMA trial. Presented at the 2013 American College of Cardiology Meeting, March 9-11, 2013, San Francisco, CA 24. Bunc M, Popovic P: Massive pulmonary embolism: Percutaneous emergency treatment using an Aspirex thrombectomy catheter. Cardiovasc Intervent Radiol 33:1052-1055, 2010
Introduction Acute pulmonary embolism (PE) is a common lifethreatening illness, with an estimated incidence of 530,000 cases in the United States per year.1 Acute PE can be stratified as high-risk or massive PE, intermediaterisk or submassive PE, and low-risk or nonmassive PE, with nearly 300,000 deaths a year attributable to PE.2 Mortality rates are high when patients present in hemodynamic shock, with reports up to 58%, and usually occur within an hour of presentation.3 Patients who survive are at risk for the development of recurrent PE or chronic thromboembolic pulmonary artery (PA) hypertension.4,5 Most deaths associated with PE are attributable to right ventricular (RV) failure.6 Patients presenting with massive PE demonstrate systemic hypotension (systolic blood pressure less than 90 mm Hg), cardiogenic shock, cardiac arrest, or RV dysfunction. Patients with submassive PE demonstrate echocardiographic and enzymatic evidence of RV dysfunction and myocardial injury but preserved systolic pressures (490 mm Hg). Patients with low-risk PE show no evidence of right-sided heart strain or myocardial injury. It is crucial to appropriately risk stratify these patients so that the treatment can be appropriately administered.
Massive PE In patients with massive PE, rapid escalation of care is imperative. The use of anticoagulation with unfractionated heparin, low-molecular-weight heparin, or fondaparinux has been advised.2,4 Intravenous infusion of the thrombolytic alteplase (IV r-tPA) (Genentech, South San Francisco, CA) at a dose of 100 mg infused over 2 hours has Food and Drug Administration approval for use in massive PE and is recommended for unstable patients with PE.7 However, after appropriate screening many patients have absolute contraindications to IV r-tPA. Even in patients who are carefully screened and without contraindications, the risk of major hemorrhage is 20% and the risk of intracranial hemorrhage is 3%-5%.4 In a large retrospective study reviewing thrombolytic therapy for massive PE, the authors found that over the past decade, only 30% of unstable patients received IV thrombolysis with an inhospital mortality rate of 15%. The remaining 70% of patients had an in-hospital mortality rate of 47%, with a pooled in-hospital mortality rate more than 37%.8 William Kuo et al in a meta-analysis of catheter-directed thrombolysis (CDT) for massive PE demonstrated a nearly 87% improvement in the clinical status. There was a major complication rate of 2.4% with only 1 reported intracranial hemorrhage among 571 patients.9
Submassive PE *Department of Radiology, Maine Medical Center, Portland, ME. †Vascular and Interventional Physicians, Spectrum Medical Group, South Portland, ME. Address reprint requests to Paul Kim, MD, Vascular and Interventional Physicians, Spectrum Medical Group, South Portland, ME. E-mail: [email protected] 1089-2516/13/$ - see front matter & 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.tvir.2014.02.010
Patients presenting with submassive PE, or intermediaterisk PE, often remain normotensive. Despite this more stable presentation, this subset of patients remains at an increased risk for adverse outcomes with mortality rates in the range of 5%-10%.10 Submassive PE is defined as maintenance of systolic blood pressures Z90 mm Hg, 121
E. Dobrow and P. Kim
122 but with echocardiographic or computed tomography evidence of right-sided heart strain as well as laboratory markers of RV strain or ischemia. On imaging with either echocardiography or pulmonary computed tomography angiography, a right-ventricular-to-left-ventricular end-diastolic ratio of Z0.9 has been demonstrated to be an independent predictor of increased mortality. This group remains at an increased risk of developing chronic PE and chronic thromboembolic PA hypertension.10-16
Rationale for CDT Although the IV infusion of r-tPA is Food and Drug Administration approved for the treatment of massive PE, it is estimated that only 30% of patients have been given this treatment over the past decade.8 Many patients have contraindications for systemic thrombolysis, and in such cases, further treatment options include surgical embolectomy, which itself has a pooled mortality rate of 19%,17 or endovascular treatment. Endovascular treatment with modern techniques has shown to be effective and safe in the treatment of massive PE, with a pooled success rate of nearly 86% with a low rate of major complications at 2.4% compared with the 20% rate of major complications from IV r-tPA.4,9 Catheter-directed fragmentation allows rapid maceration of large, central pulmonary emboli, which has the dual effect of increasing pulmonary perfusion and decreasing PA pressures, thereby decreasing RV strain. The most frequent mechanical technique employs clot fragmentation with the rotating pigtail catheter.17-19 Endovascular treatments can be tailored based on the clinical risk of bleeding so that, if able, pharmacologic treatments can be combined with catheter treatments to administer lower overall doses of thrombolytic agent directly into the thrombus as compared with IV thrombolysis. Flow studies have validated the concept that intrathrombus infusion of the thrombolytic agent improves thrombolysis by demonstrating that obstructing pulmonary emboli causes alteration in hemodynamics such that the drug administered upstream is prevented from making contact with its intended target, with rapid washout of the drug through nonobstructed pulmonary arteries.20 The intrathrombus infusion can be delivered using a standard infusion catheter or in combination with high-frequency, low-power ultrasound waves with the EKOS system. This technology has the added benefit of causing the fibrin strands to thin and loosen, thus allowing greater exposure of plasminogen receptor sites, as well as increasing thrombus permeability, which can result in greater penetration of the drug.21 Data also suggest that more aggressive treatment of submassive PE with a thrombolytic may result in lower short-term morbidity and likelihood of clinical deterioration during the hospital stay.22 The ULTIMA trial and a recent retrospective study by Kennedy et al have shown that pharmacomechanical thrombolysis with the EKOS ultrasound-accelerated infusion catheter is both safe and effective at reversing RV dysfunction at 24 hours and at
90 days, without the associated risks of full-dose systemic thrombolysis.21,23
Endovascular Treatment of Submassive and Massive PE Submassive PE Given that these patients have overall low in-hospital mortality, it is important to document that they have signs of a PE that are significant enough to warrant endovascular treatment. The trigger for using an endovascular approach for treating these patients is evidence of right-sided heart strain based on either echocardiography or computed tomography angiography imaging. If they have signs of right-sided heart strain and PE and are willing to undergo endovascular treatment, we plan for CDT. Because most of these patients are hemodynamically stable, we treat these procedures as urgent but not emergent (ie, start treatment within 24 hours of consultation). We perform these procedures under moderate sedation using IV fentanyl and midazolam. Upon obtaining bilateral common femoral vein access, we often place a retrievable inferior vena cava (IVC) filter in the infrarenal IVC in patients who have a deep venous thrombosis. Our reasoning for placing a filter is that these patients have a significant-enough burden of thrombus, causing rightsided heart dysfunction for which additional protection in the acute phase is reasonable. An alternative singleaccess option includes using a 12-F dual-lumen or 14-F triple-lumen sheath (St. Jude). We then use a variety of pulmonary catheters (APC, Grolman, Cook Medical, Bloomington, IN) to select the main PA. On obtaining PA pressure measurements, we select the right and left pulmonary arteries in sequential fashion. Because the PA pressures are high enough to preclude the use of a power injection, hand injections of 15 mL of iodinated contrast (Omnipaque 350, GE Healthcare) are administered at a high frame rate (6-7 frames per second), as these patients are sometimes unable to perform an adequate breath hold. After placement of a stiff-exchange length wire, an 8-F, 65-cm sheath (Destination sheath, Terumo, Somerset, NJ) is advanced either to the main PA or into the right or left PA. Using an angled catheter and glide wire, the most involved branch or segment of each PA is selected. The catheter is then exchanged for a 12-cm infusion-length catheter for ultrasound-accelerated thrombolysis (BTGEKOS Corporation, Bothell, WA). In an identical fashion, the same steps are performed for selecting the thrombosed segments of the contralateral PA, and a second infusion catheter is placed. Alteplase (Genentech, San Francisco, CA) infusion is started at 0.5 mg/h on each side for a total dose of 1 mg/h (Fig. 1). Systemic unfractionated heparin is administered during thrombolysis to maintain a partial thromboplastin time of 50-65 seconds. These patients are monitored overnight in an intensive care unit or in a step-
Endovascular treatment of massive and submassive pulmonary embolism
123
Figure 1 A 38-year-old man after undergoing urologic surgery 6 hours prior presents with a massive PE. (A) Right pulmonary angiogram demonstrates upper lobe thrombus. (B) A 6-mm balloon angioplasty performed with mildly improved perfusion. (C) Rheolytic thrombectomy performed with AngioJet (arrow). (D) Resolution of thrombus in affected pulmonary artery.
down unit that is trained in the care of patients undergoing thrombolysis. After approximately 24 hours of infusion, the patient is brought back to the procedure room. Changes in oxygen requirement, patient’s symptoms, and vital signs are documented. After removing the EKOS catheters over a wire, PA pressures are remeasured through the sheaths. Repeat pulmonary angiograms are performed. The interventionalist then determines if thrombolysis should be terminated. If the PA pressures remain significantly elevated, we may elect to continue infusion or reposition the catheter into another thrombosed segment. The maximal duration of thrombolysis in our experience has been 48 hours. We obtain a repeat echocardiogram 24 hours after completion of thrombolysis to document the
improvement in RV diameter and function. The patients are transitioned to oral anticoagulation. We routinely use low-molecular-weight heparin and warfarin for a minimum duration of 6 months. A follow-up of these patients is conducted in 3 months at our clinic to assess their clinical status and also to evaluate them for potential IVC filter retrieval at that time.
Massive PE At our institution, patients with suspected massive PE are quickly evaluated for contraindications to systemic thrombolysis. If they are not excluded, they are administered a bolus of tenecteplase IV (0.5 mg/kg with a maximum dose of 50 mg) (Genentech, San Francisco, CA). Although the application of tenecteplase for PE at this time is off label, it
124
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Figure 2 A 66-year-old woman with a submassive PE. (A and B) Bilateral angiograms demonstrate significant clot burden and PA systolic pressure of 58 mm Hg. (C) Placement of bilateral EKOS catheters into right upper and left lower lobes. (D and E) Twenty-four hours later, improvement in perfusion was seen with decrease in main PA pressure to 26 mm Hg.
Endovascular treatment of massive and submassive pulmonary embolism may be a promising alternative to alteplase as it has the benefit of a more rapid delivery than systemic alteplase and has a greater specificity for fibrin. If the patients remain hypotensive or are excluded from systemic thrombolysis, interventional radiology is consulted for emergent thrombectomy. Because of the potential rapid and escalating mortality associated with massive PE, we bring the patient to the angiography suite immediately. The initial setup and steps are similar to our approach to submassive PE with an IVC filter placed followed by catheterization of the PAs with pressure measurements and hand injection angiograms. However, the end point is different, in that our primary goal is to debulk the volume of thrombus proximally so as to allow for some degree of pulmonary venous return to the left side of the heart to allow for systemic perfusion. Therefore, we begin with mechanical thrombectomy. On selection of the thrombosed pulmonary arteries, mechanical fragmentation is attempted with either a pigtail catheter or a balloon maceration. A balloon is undersized relative to the PA to reduce the risk of rupture. Typically a balloon with a diameter of 6-8 mm is used for segmental branches and a balloon with a diameter of 8-12 mm is used for right and left main pulmonary arteries (Fig. 2). Aspiration through the guide sheath is also performed intermittently to remove any mobile or liquefied thrombus. Although controversial, rheolytic thrombectomy with the Solent Omni AngioJet catheter (MedRad, Minneapolis, MN) is employed on occasions when the methods described earlier are not sufficient. We use short (1-2 second) pulses with close attention paid to the electrocardiogram tracings to watch for bradycardia or asystole (Fig. 2). Epinephrine and atropine should be readily available to intervene if necessary. In our experience, no patients have suffered from sustained bradycardia or had an adverse cardiac event secondary to AngioJet thrombectomy utilization in the pulmonary arteries. We have used the AngioJet Solent and AVX catheters to perform thrombectomy in both central and segmental pulmonary arteries. Perforations of vessels beyond the central pulmonary arteries have been reported, and, therefore, extreme care must be taken when treating these vessels. We commonly use boluses of alteplase during thrombectomy procedures. Despite the fact that some patients were excluded from systemic thrombolysis (usually secondary to recent surgery or trauma), we use boluses of alteplase weighing 8-12 mg to a maximum of 20 mg during the procedure. In our experience, no patient has had a significant hemorrhage (requiring transfusion or intracranial hemorrhage) despite using these boluses in seemingly high-risk patients for bleeding. The primary end point is improvement in systemic blood pressure and decrease in PA pressure. If there remains a significant clot burden despite pharmacomechanical attempts, we leave an EKOS infusion catheter for continued thrombolysis at 0.5 mg/h per lung. At this point, the algorithm is similar to that for the patients with submassive PE and they are brought back at 24 hours for repeat PA pressure measurements and angiograms.
125
If the patient with massive PE survives until discharge, we set up an appointment with him or her at 6 weeks postdischarge for clinical follow-up and discussion of potential IVC filter retrieval.
Alternative Thrombectomy Devices The Aspirex catheter (Straub Medical, Wangs, Switzerland) is an over-the-wire (035 in) thrombectomy device indicated for use in the peripheral circulation that uses high-speed rotation and fragmentation aspiration to remove thrombus. Although its Instructions for Use warns against the use of this device in the pulmonary circulation, there are case reports that show some promise in treating PE.24 The Helix Thrombectomy Device (ev3/Covidien) is a 7-F device indicated for removal of clot from dialysis arteriovenous fistula and grafts, which directs a highpressure impeller outflow to the vessel wall with ongoing active aspiration. Mechanical thrombectomy devices such as the Trerotola device (Arrow International) or Cleaner (Argon Medical, Plano, TX) are also approved for thrombectomy of clotted dialysis arteriovenous fistulae and grafts and use direct mechanical disruption of the thrombus for maceration. These devices do not run over the wire, and care must be taken to avoid dissection, perforation, and arrhythmias. AngioVac (Angiodynamics, Latham, NY) is a filtering system used as an adjunct to extracorporeal bypass. It is a 22-F catheter with a balloon-activated distal tip shaped like a funnel. During bypass, active aspiration of the venous flow extends through the filtering system that eliminates all debris from the circulation before returning blood flow to the patient. A perfusionist is required to assist with the bypass portion of the procedure. Although only case reports exist at this time, it appears to be a rapid endovascular method to remove large volumes of thrombus from large veins and the pulmonary arteries.
Conclusion Endovascular therapy has growing evidence for its utilization as part of the treatment algorithm for submassive and massive PE. There are a variety of techniques available for removing or reducing thrombus within the pulmonary circulation. Catheter-based techniques appear to be successful and safe in treating both massive and submassive PE.
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