Surgical Pulmonary Embolectomy

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1 Clinician Update Surgical Timothy J. Poterucha, MD; Brian Bergmark, MD; Sary Aranki, MD; Tsuyoshi Kaneko, MD; Gregory Piazza, MD, MS Case Presentation A 66-year-old man with a recent prosthetic knee infection, status post prosthesis removal, was admitted with recurrent septic arthritis. On his seventh hospital day, as he was signing his discharge paperwork, he developed acute respiratory distress. On physical examination, he was tachycardic to 118 beats/min, relatively hypotensive from 144/78 mm Hg earlier in the day to 94/54 mm Hg, and hypoxemic, with an oxygen saturation of 94% on a 100% nonrebreather facemask. The ECG showed sinus tachycardia. An urgent contrast-enhanced chest computed tomogram (CT) demonstrated large saddle pulmonary embolism (PE) and severe right ventricular (RV) enlargement, with an RV diameterto-left ventricular (LV) diameter ratio of 1.8 (Figure 1). The patient was administered a bolus of intravenous unfractionated heparin followed by a continuous infusion. An urgent bedside transthoracic echocardiogram showed severe RV dilation, moderateto-severe pulmonary hypertension, and RV pressure overload as suggested by systolic deviation of the interventricular septum toward the LV (Figure 2). The Vascular Medicine and Cardiac Surgery services were consulted for consideration of advanced therapies. Because of concern for major bleeding associated with fibrinolytic therapy in the setting of recent major surgery, surgical pulmonary embolectomy was recommended. Introduction Despite advances in diagnostics and therapeutics, acute PE remains a life-threatening condition with an in-hospital mortality rate of 7% for all-comers and 31% for patients with hemodynamically unstable (massive) PE. 1 Current management algorithms emphasize risk stratification to identify patients who may benefit from early advanced therapies in addition to anticoagulation. 2 4 Risk categories of massive, submassive, and low-risk PE are based on clinical, radiological, and laboratory criteria. Massive PE is characterized by systemic arterial hypotension, syncope, cardiogenic shock, cardiac arrest, or respiratory failure. Submassive PE is defined by evidence of RV dysfunction on imaging (RV/LV diameter >0.9 on contrastenhanced chest CT or RV dilation and hypokinesis on echocardiography), elevated cardiac biomarkers (such as cardiac troponin), or both, in a patient with preserved systemic arterial pressure. Submassive PE comprises a patient population at increased risk of adverse outcomes and early mortality. Low-risk PE patients have none of these features and typically have an uneventful clinical course when treated with therapeutic anticoagulation alone. Advanced therapies are often considered for patients with submassive or massive PE to rapidly relieve RV pressure overload and avert hemodynamic deterioration. Advanced therapies for reperfusion include systemic fibrinolysis, catheter-based pharmacomechanical intervention, and surgical pulmonary embolectomy. A recent meta-analysis showed a 1.7% absolute mortality From Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA (T.J.P.); Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA (B.B., G.P.); and Division of Cardiac Surgery, Department of Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA (S.A., T.K.). The online-only Data Supplement is available with this article at /-/DC1. Correspondence to Gregory Piazza, MD, MS, Cardiovascular Division, Brigham and Women s Hospital, 75 Francis St, Boston, MA gpiazza@partners.org (Circulation. 2015;132: DOI: /CIRCULATIONAHA ) 2015 American Heart Association, Inc. Circulation is available at DOI: /CIRCULATIONAHA

2 Poterucha et al Surgical 1147 Figure 1. Contrast-enhanced chest computed tomogram (CT) demonstrating acute pulmonary embolism (PE) in a 66-year-old man who developed sudden dyspnea, severe hypoxemia, and relative hypotension. Coronal views demonstrating a large, dense filling defect straddling the bifurcation of the main pulmonary artery consistent with saddle PE (A) and extending into the right and left main pulmonary arteries (arrows, B). Axial view demonstrating a right ventricular (RV) diameter of 4.8 cm in comparison with 2.6 cm for the left ventricle (LV; RV-to-LV diameter ratio of 1.8; normal <0.9) consistent with severe RV enlargement (C). benefit with systemic fibrinolysis versus anticoagulation alone in submassive PE, but this was achieved with the cost of a 6% absolute increase in the rate of major bleeding, including a 1.5% rate of intracranial hemorrhage. 5 The intracranial hemorrhage rate with systemic fibrinolysis has been estimated to be 3% in the real-world experience of the International Cooperative Pulmonary Embolectomy Registry, which included all patients with acute PE. 6 Fear of the risk of intracranial hemorrhage associated with systemic fibrinolysis has driven strong interest in alternative therapies to rapidly relieve RV pressure overload, while minimizing the risk of intracranial hemorrhage. Although catheter-based pharmacomechanical therapy is emerging as a promising strategy, surgical pulmonary embolectomy has been available for several decades as an option for the 40% of patients with PE who have at least 1 contraindication to systemic fibrinolysis. 7 As surgical techniques, experience, and perioperative care have improved, the potential to expand the role of surgical pulmonary embolectomy has grown. Historical Use of Surgical The first successful surgical pulmonary embolectomy was performed in Germany in 1924 by Dr Martin Kirschner, and cardiopulmonary bypass was incorporated when it became available in the 1960s. 8 Surgical mortality rates in the middle-to-late 20th century exceeded 30%, resulting in the restriction of surgical pulmonary embolectomy to patients in refractory shock with no other options. 9 The observation that surgical pulmonary embolectomy was rarely associated with favorable outcomes led to the conclusion that patients who died during the operation were too ill to undergo surgery, whereas those who survived surgery were well enough that they should have been managed medically. 10 As a result, the operation was doomed to failure, with patients being considered too sick or too well to undergo surgical pulmonary embolectomy. The technique was abandoned at most hospitals in the 1980s to 1990s. During this time, surgical techniques were refined in a small number of centers and outcomes began to improve. A study by Gulba et al 11 showed a 77% survival rate with surgical pulmonary embolectomy in patients with shock from PE, which was comparable to the 67% survival rate demonstrated with fibrinolytic therapy. In a cohort of 24 patients with circulatory collapse, including nearly half who were resuscitated from a cardiac arrest, Takahashi et al 12 reported a 5-year survival rate of 87.5%. In addition, this cohort had excellent long-term recovery, with estimated pulmonary artery systolic pressures decreasing from a mean of 66.9 to 28.5 mm Hg. The evidence for favorable outcomes with surgical pulmonary embolectomy in massive PE has led to an increase in the use of surgical pulmonary embolectomy as first-line treatment rather than as rescue therapy. Surgical Pulmonary Embolectomy in Submassive PE With the encouraging outcomes data for surgical pulmonary embolectomy in the treatment of massive PE, some experts have advocated that surgical pulmonary embolectomy could be a valid option for patients with submassive PE at high risk for adverse outcomes or with contraindications to fibrinolysis. 10 In 2002, Aklog et al 13 published their results of surgical pulmonary embolectomy in a series of 29 patients with submassive PE, with evidence of moderate-to-severe RV dysfunction, showing an 89% 1-month survival. Notably, this was a singlecenter study with a dedicated team of a single cardiologist and 2 cardiothoracic surgeons available 24 hours a day, and the surgery was performed without the use of cardioplegia or aortic cross-clamping. The first patients treated in this cohort had a high rate of recurrent PE, resulting in life-threatening decompensation, and inferior vena cava (IVC) filter placement was

3 1148 Circulation September 22, 2015 Figure 2. Transthoracic echocardiogram, apical 4-chamber view, demonstrating right ventricular (RV) and right atrial (RA) dilation and RV pressure overload with interventricular septal deviation toward the left ventricle (LV; arrows) in a 66-year-old man diagnosed with acute saddle pulmonary embolism (A). Color Doppler interrogation of the tricuspid valve demonstrating moderate-to-severe tricuspid regurgitation (blue; B). Pulse wave Doppler of the tricuspid valve regurgitant jet demonstrating an estimated pulmonary artery systolic pressure of 67 mm Hg (47 mm Hg plus an estimated RA pressure of 20 mm Hg; C). LA indicates left atrium. associated with reduced PE recurrence and improved outcomes. A subsequent report from the same center in 2005 with 47 patients showed a 6% operative mortality and 86% 1-year survival. 14 Greelish et al 15 reported a case series in 2011 of 107 patients with central PE in which 15 patients were treated surgically and 88 medically. In this cohort, 47% of patients treated with surgery had hypotension on presentation in comparison with 8% in the medical management group. Despite the higher acuity among the patients in the surgical group, their survival was improved, with 29% of patients in the surgical arm and 43% of patients in the medical management arm dying within the first 30 days. Both deaths in the surgical group occurred in patients requiring preoperative cardiopulmonary resuscitation. Similar to the experience of Aklog et al, 13 nearly all patients in the surgical arm had IVC filters placed perioperatively. The largest case series of surgical embolectomy by Neely et al 16 shows that outcomes for surgical pulmonary embolectomy have continued to improve. In a series of 115 patients undergoing surgical pulmonary embolectomy, the authors report an overall mortality rate of 6.6%. Notably, this study included 56 patients with submassive PE who underwent surgical pulmonary embolectomy because of contraindications to fibrinolysis, failure of catheter-based therapies, or severe RV dysfunction. In the subgroup of patients with submassive PE, the operative mortality rate was 3.6%. Recent registry data have suggested improved survival for patients with massive PE who proceed directly to surgical pulmonary embolectomy, rather than reserving surgical pulmonary embolectomy for those in whom fibrinolysis is unsuccessful. 17 With short-term surgical mortality rates ranging from 3.6% to 13% in the most recent studies, the potential of firstline surgical pulmonary embolectomy as an alternative to systemic fibrinolysis has expanded. Indications for Surgical The American Heart Association, American College of Chest Physicians, and European Society of Cardiology recommend surgical pulmonary embolectomy for patients with massive PE and contraindications to fibrinolysis who have surgically accessible, centrally located PE (Table 1). 2 4 Contraindications for systemic fibrinolysis include active bleeding, recent ischemic stroke, any past history of

4 Poterucha et al Surgical 1149 Table 1. Major Indications for Surgical Massive or submassive centrally located pulmonary embolism with any of the following: Contraindication to fibrinolytic therapy Active bleeding Failed fibrinolysis or catheter-based therapy Clot-in-transit Large patent foramen ovale Moderate-to-severe right ventricular dysfunction hemorrhagic stroke, and surgery within the past month (Table 2). 2 In addition to those patients with contraindications to fibrinolysis, there are 4 other patient populations traditionally considered for surgical pulmonary embolectomy. Patients with massive or submassive PE in whom systemic or catheter-based therapies have failed are appropriate candidates for surgical pulmonary embolectomy. These patients are at increased risk for further clinical deterioration, and those patients who proceed directly to surgery have improved outcomes in comparison with those who undergo repeat fibrinolysis. 18 When considering surgical pulmonary embolectomy after failed fibrinolysis, the urgency of the need for intervention must be weighed against the risk of bleeding. Second, patients with clot-in-transit in the right atrium or RV have an estimated mortality rate of 29% and are at high risk for abrupt hemodynamic deterioration, often without warning and with little time to administer fibrinolytic therapy or mobilize an interventional cardiology team (Figure 3 and Movie I in the online-only Data Supplement). 19 Third, patients with a large patent foramen ovale have worse outcomes than patients without, with relative risks of death and ischemic stroke of 2.4 and 5.9, respectively. 20 Proceeding to surgery rather than attempting fibrinolysis allows for an opportunity to repair the patent foramen ovale to prevent paradoxical embolism in the future. Finally, patients with submassive PE and moderate-to-severe right heart strain may benefit from the immediate hemodynamic improvement in pulmonary vascular resistance and RV pressure overload provided by surgical pulmonary embolectomy Imaging Evaluation of Patients Undergoing Surgical The imaging test of choice for PE is contrast-enhanced CT. In addition to making the diagnosis of PE, CT also provides anatomic information that identifies the location and extent of the PE. Large central PE is defined as being present within the lateral mediastinal borders and will be accessible through surgical pulmonary embolectomy, whereas small peripheral PE will not be. 15 For patients with a PE identified by using ventilation-perfusion lung scanning who cannot undergo contrast-enhanced CT owing to a dye allergy or other contraindications, transesophageal echocardiography can be used to assess for clot-in-transit or the presence of PE in the proximal pulmonary arteries. If the anatomy is not clear to the surgical team, imaging should be reviewed with experienced chest or cardiovascular imaging specialists. Often, multiplanar reformatted images provide additional information to guide the operative approach. Table 2. Major Contraindications to Systemic Fibrinolysis Active bleeding Recent neurological, spinal, or craniofacial surgery or injury to the head or face Any past history of intracranial hemorrhage Intracerebral malignancy, mass, aneurysm, or arteriovenous malformation Ischemic stroke within the past 3 mo Major surgery within the past month Noncompressible vascular punctures or trauma Prolonged cardiopulmonary resuscitation Current severe hypertension or past history of prolonged severe hypertension Age >75 y or dementia Pregnancy Management of Patients Undergoing Surgical On diagnosis of PE, all patients without contraindications should be administered immediate therapeutic dose anticoagulation to prevent thrombus propagation and further embolic events. Intravenous unfractionated heparin administered as a bolus and then an infusion titrated to an activated partial thromboplastin time of 60 to 80 seconds is preferred if surgical pulmonary embolectomy is being considered. Continuous infusion intravenous unfractionated heparin allows for hour-to-hour control of the intensity of anticoagulation. During cardiopulmonary bypass, an activated clotting time target of 480 seconds is required. Typically, a pulmonary arteriotomy is made longitudinally in the main pulmonary artery distal to the pulmonic valve and short of the pulmonary artery bifurcation. A saddle PE will be visualized via this incision, and gentle traction is often successful in removing the saddle PE and associated left pulmonary artery thrombus. If residual thrombus is suspected in the right pulmonary artery, an additional incision can be made in the right pulmonary artery between the aorta and superior vena cava to retrieve additional thrombus. Blind exploration of the fragile pulmonary arteries should be avoided. Centers offering surgical pulmonary embolectomy should not only have expertise in performing the surgery, but also experience in the postoperative support of these patients and management of potential complications. Major complications can include persistent RV dysfunction, resulting in failure to wean from cardiopulmonary bypass, and cardiac tamponade, sternal wound infection, and postoperative bleeding, as well. Multiple studies have documented a high rate of recurrent PE in patients after surgical pulmonary embolectomy, and these events can be life-threatening in the presence of preexisting RV failure In the International Cooperative Registry, patients who underwent IVC filter placement had a lower 90-day mortality, 21 and it has become standard

5 1150 Circulation September 22, 2015 as surgical pulmonary embolectomy when appropriate. Figure 3. Transthoracic echocardiogram, apical 4-chamber view, showing clot-in-transit (arrows) extending from the right atrium (RA) into the right ventricle (RV). The RV is dilated. LA indicates left atrium; and LV, left ventricle. practice at some centers to insert IVC filters intraoperatively or immediately postoperatively in patients who undergo surgical pulmonary embolectomy Whether and when to retrieve IVC filters inserted perioperatively remains subject to debate. Postoperatively, anticoagulation should be restarted promptly to prevent propagation of deep vein thrombosis or distal PE. Oral anticoagulation is then instituted with warfarin or a non vitamin K antagonist oral anticoagulant. The duration of anticoagulation should take into account the circumstances surrounding the PE. However, extended-duration anticoagulation is often considered in unprovoked (idiopathic) PE or in patients with lifethreatening PE presentation. PE Response Teams Because of the complexities of patient selection for advanced therapies in acute PE, many centers have instituted multidisciplinary PE response teams. These teams bring together experts in cardiovascular medicine, cardiothoracic surgery, echocardiography, emergency medicine, radiology, and pulmonology to select appropriate patients for advanced therapies and to determine the optimal reperfusion strategy. The use of these multidisciplinary teams may allow rapid access to advanced therapies such Figure 4. Gross pathological specimen from surgical pulmonary embolectomy in 66-yearold man with a saddle pulmonary embolism. Case Follow-Up The patient underwent successful urgent surgical pulmonary embolectomy (Figure 4). With rapid improvement in his oxygenation and hemodynamic status, he was extubated the following morning. An IVC filter was placed postoperatively. At the time of hospital discharge, the patient was transitioned from intravenous unfractionated heparin to oral rivaroxaban 20 mg daily. In vascular medicine clinic follow-up, he had returned to his baseline functional status and was free of dyspnea. None. Disclosures References 1. Casazza F, Becattini C, Bongarzoni A, Cuccia C, Roncon L, Favretto G, Zonzin P, Pignataro L, Agnelli G. Clinical features and short term outcomes of patients with acute pulmonary embolism. The Italian Pulmonary Embolism Registry (IPER). Thromb Res. 2012;130: doi: /j. thromres Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123: doi: /CIR.0b013e f. 3. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR; American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e419s e494s. doi: /chest Konstantinides SV ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35: doi: /eurheartj/ ehu393.

6 Poterucha et al Surgical Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, Kumbhani DJ, Mukherjee D, Jaff MR, Giri J. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a metaanalysis. JAMA. 2014;311: doi: /jama Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353: Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD, Rauber K, Iversen S, Redecker M, Kienast J. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol. 1997;30: McFadden PM, Ochsner JL. Aggressive approach to pulmonary embolectomy for massive acute pulmonary embolism: a historical and contemporary perspective. Mayo Clin Proc. 2010;85: doi: / mcp Meyer G, Tamisier D, Sors H, Stern M, Vouhé P, Makowski S, Neveux JY, Leca F, Even P. Pulmonary embolectomy: a 20-year experience at one center. Ann Thorac Surg. 1991;51: Goldhaber SZ. Surgical pulmonary embolectomy: the resurrection of an almost discarded operation. Tex Heart Inst J. 2013;40: Gulba DC, Schmid C, Borst HG, Lichtlen P, Dietz R, Luft FC. Medical compared with surgical treatment for massive pulmonary embolism. Lancet. 1994;343: Takahashi H, Okada K, Matsumori M, Kano H, Kitagawa A, Okita Y. Aggressive surgical treatment of acute pulmonary embolism with circulatory collapse. Ann Thorac Surg. 2012;94: doi: /j. athoracsur Aklog L, Williams CS, Byrne JG, Goldhaber SZ. Acute pulmonary embolectomy: a contemporary approach. Circulation. 2002;105: Leacche M, Unic D, Goldhaber SZ, Rawn JD, Aranki SF, Couper GS, Mihaljevic T, Rizzo RJ, Cohn LH, Aklog L, Byrne JG. Modern surgical treatment of massive pulmonary embolism: results in 47 consecutive patients after rapid diagnosis and aggressive surgical approach. J Thorac Cardiovasc Surg. 2005;129: doi: /j. jtcvs Greelish JP, Leacche M, Solenkova NS, Ahmad RM, Byrne JG. Improved midterm outcomes for type A (central) pulmonary emboli treated surgically. J Thorac Cardiovasc Surg. 2011;142: doi: /j.jtcvs Neely RC, Byrne JG, Gosev I, Cohn LH, Javed Q, Rawn JD, Goldhaber SZ, Piazza G, Aranki SF, Shekar PS, Leacche M. Surgical embolectomy for acute massive and submassive pulmonary embolism in a series of 115 patients (published online ahead of print July 10, 2015). Ann Thorac Surg. doi: /j. athoracsur Aymard T, Kadner A, Widmer A, Basciani R, Tevaearai H, Weber A, Schmidli J, Carrel T. Massive pulmonary embolism: surgical embolectomy versus thrombolytic therapy should surgical indications be revisited? Eur J Cardiothorac Surg. 2013;43:90 94; discussion 94. doi: /ejcts/ezs Meneveau N, Séronde MF, Blonde MC, Legalery P, Didier-Petit K, Briand F, Caulfield F, Schiele F, Bernard Y, Bassand JP. Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Chest. 2006;129: doi: /chest Torbicki A, Galié N, Covezzoli A, Rossi E, De Rosa M, Goldhaber SZ; ICOPER Study Group. Right heart thrombi in pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry. J Am Coll Cardiol. 2003;41: Konstantinides S, Geibel A, Kasper W, Olschewski M, Blümel L, Just H. Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism. Circulation. 1998;97: Kucher N, Rossi E, De Rosa M, Goldhaber SZ. Massive pulmonary embolism. Circulation. 2006;113: doi: /CIRCULATIONAHA Key Words: anticoagulation embolectomy pulmonary embolism venous thromboembolism

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