Surgical Pulmonary Embolectomy for Massive and Submassive Pulmonary Embolism

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1 Research Article Karol Mudy, MD Daniel J. DiBardino, MD Judah A. Askew, MD Benjamin K. Sun, MD From: Minneapolis Heart Institute at Abbott Northwestern Memorial Hospital, Minneapolis, MN Address for correspondence: Karol Mudy, MD Minneapolis Heart Institute 920 E 28th Street, Suite 400 Minneapolis MN Karol.Mudy@allina.com Surgical Pulmonary Embolectomy for Massive and Submassive Pulmonary Embolism ABSTRACT Acute pulmonary embolism remains a common and undertreated cause of death. Treatment modalities for massive and submassive pulmonary embolism vary from an institution to institution. Surgical pulmonary embolectomy is nowadays a wellestablished, safe operation, with good short and long term results, when performed by an experienced surgeon. We review the most current medical, surgical and catheter treatment options and results, and discuss our most recently adopted algorithm. When applied within a rapidly executed, coordinated, well-defined approach, the surgical treatment provides excellent results for massive acute pulmonary embolism and the highest freedom from chronic residua. A multidisciplinary algorithm agreed upon our hospital stakeholders such as the emergency department, cardiology and cardiac surgery can streamline the approach, reduce error and hopefully improve survival. KEY WORDS pulmonary embolism, pulmonary embolectomy, thrombolysis, catheter-directed intervention n INTRODUCTION Pulmonary embolism (PE) is the third most common cause of death in United States after primary cardiac conditions and cancer. 1 It is half as common as acute myocardial infarction and three times more common than cerebrovascular accident. 1 Even given these staggering numbers, the true prevalence is most likely underestimated, since many patients are diagnosed postmortem. 2,3 When properly and promptly treated, PE is a potentially curable condition with minimally long-term sequelae. 6 We review the spectrum of presentation and recommended treatment, the latest results and present our resulting multidisciplinary approach. Evolution of Treatment The mainstay of treatment for most PE has historically been and remains anticoagulation with thrombolytic or procedural intervention (transcatheter or surgical) reserved for massive and submassive cases in which instability results. 5 According to the American Heart Association, massive PE is defined as acute PE with hypotension (systolic blood pressure less than 90 mm Hg) for at least 15 minutes or requiring inotropic support that is not due to other cause, pulselessness, or persistent bradycardia with the heart rate less than 40 beats/minute and with signs of shock. Submassive PE is defined as acute PE without hypotension (systolic blood pressure greater than 90 mm Hg), but with either right ventricular (RV) dysfunction or signs of myocardial necrosis. 8 Systemic thrombolytic therapy has a well-established place for PE with hemodynamic instability and serious RV strain. 5 At traditional dosing levels, it carries a relatively high risk of hemorrhagic complications including intracranial bleeds. When a lower dose is used in moderate pulmonary embolism (moderate pulmonary embolism treated with thrombolysis, MOPETT trial), no increased bleeding risk exists, when compared with standard anticoagulation. 9 With a more recent reduced dosing regimen, the efficacy of thrombolytic therapy seems to remain the same with decreased rates of hemorrhagic complications. 9 Ó 2018 Minneapolis Heart Institute Foundation For the patients with contraindications to systemic thrombolysis but who require aggressive therapy for instability, catheter-based intervention has become an alternative. Many devices are available that are based on either providing directed continuous thrombolytic delivery into the clot or fragmentation and/or evacuation of the thrombus with suction. They allow more aggressive treatment of hemodynam- 44 JOURNAL OF THE MINNEAPOLIS HEART INSTITUTE FOUNDATION n Volume 2 n Issue 1 n Spring/Summer 2018

2 ically unstable patients, with higher clot burden. Unfortunately, there are no large prospective or retrospective studies comparing head-to-head catheterbased therapy to surgical embolectomy. Kuo et al 10 showed very good results with catheterdirected therapy, with the use of mechanical fragmentation, aspiration, and hourly infusion of a thrombolytic agent (tissue plasminogen activator or urokinase). This study was based on a real-world prospectively collected data from a multicenter registry. It included 101 patients with PE (28 with massive and 73 with submassive). Clinical success (defined as stabilization of hemodynamics, improvement in pulmonary hypertension, right-sided heart strain, or both, and survival to hospital discharge) was achieved in 24 of 28 patients with massive PE (85.7%; 95% confidence interval [CI]: 67.3% 96.0%) and 71 of 73 patients with submassive PE (97.3%; 95% CI: 90.5% 99.7%). The mean pulmonary artery pressure improved from to mm Hg (n ¼ 92; P,.0001). Among patients monitored with follow-up echocardiography, 57 of 64 (89.1%; 95% CI: 78.8% 95.5%; P,.0001) showed improvement in right-sided heart strain. There were no major procedure-related complications, major hemorrhages, or hemorrhagic strokes. There were 6 (5.9%) in-hospital deaths (4 in massive and 2 in submassive group). Koucher and colleagues 11 showed improved results with ultrasound-assisted catheter-directed thrombolysis (USAT) combined with unfractionated heparin when compared to unfractionated heparin alone in intermediate-risk patients with acute pulmonary embolism. The reduction of RV dilation at 24 hours was significantly better in the USAT plus heparin group versus heparin alone. Catheter-directed therapy has its important role in treating patients with massive and submassive pulmonary embolism. It improves short-term hemodynamics and right ventricular performance. There is still paucity of long-term data following catheter-directed therapies. One of the large retrospective reviews of 2060 PE patients who were treated with thrombolytic therapy, out of which 591 (28.69%) with catheter-directed and 1469 (71.31%) with systemic thrombolysis, showed the former to be superior in terms of in hospital mortality and major bleeding complications. 12 Surgical pulmonary embolectomy for acute PE was historically considered a high mortality procedure. 13 The older data demonstrated that results were similar when compared to a standard anticoagulation or anticoagulation combined with thrombolysis. 14 Perspective is important, however. Much of this data came from the days when cardiopulmonary bypass itself carried a high risk of perioperative complications. MUDY ET AL Technology has significantly improved and the technique significantly refined. Greelish et al 6 showed superior long-term survival in patients with a central (type A) pulmonary embolus treated surgically comparing to patients treated medically for a central embolic disease (92% at 1 and 3 year follow-up for a surgical versus 74% and 66.6% at 1 and 3 year follow-up for a medical group, respectively [P ¼.0001]). Takahashi and colleagues 7 show excellent results of surgically treated patients with a massive pulmonary embolism and cardiovascular collapse. They presented a series of 24 patients that underwent pulmonary embolectomy between 2000 and 2011; 16 of those 24 patients (66.7%) required preoperative percutaneous cardiopulmonary support. Despite such a sick group of patients, authors achieved 87.5% in-hospital survival, with no late (5-year follow-up) deaths. The latest data show pulmonary embolectomy providing a high technical success rate, low mortality and good long-term results. 4,6 Neely and colleagues 4 reported 6.6% (7 of 105) operative mortality for a cohort of 105 patients operated for a massive and submassive pulmonary embolism, with 10.2% (5 of 49) mortality for unstable patients, and 3.6% (2 of 56) for the stable ones. Survival rates at 6 months, 1 year, and 3 years were estimated at, respectively, 75%, 68.4%, and 65.8% for massive PE, versus 92.6%, 86.7%, and 80.4% for submassive PE (P ¼.018). 4 The results of surgical pulmonary embolectomy varied over decades. We reiterate the data above that in the modern era the results of surgery under these conditions are very good with the best possible long-term outcomes. There are no prospective randomized controlled trials comparing surgical pulmonary embolectomy with catheter therapy or medical management in massive pulmonary embolism. One of the largest retrospective series comes from Brigham and Women s Hospital, where the authors describe a series of 105 patients undergoing pulmonary embolectomy for a central embolus. 4 The short- and long-term results are excellent with an operative mortality of 6.6% for the whole group (7 of 105 patients); 10.2% (5 of 49) for unstable patients; and 3.6% (2 of 56) for the stable ones, with no statistical difference (P ¼.247) between groups. Massive and Submassive PE; the Place for Surgery Based on the Chest Guidelines and Expert Panel Report from 2016, 5 the mainstay treatment strategy for massive pulmonary embolism is systemic anticoagulation and systemic thrombolytic therapy. If contraindications to fibrinolysis exists (Table 1), then catheter-based intervention is recommended. We reiterate that despite many advancements in technology, results of catheter- JOURNAL OF THE MINNEAPOLIS HEART INSTITUTE FOUNDATION n Volume 2 n Issue 1 n Spring/Summer

3 SURGICAL PULMONARY EMBOLECTOMY TABLE 1 Contraindications for systemic thrombolytic therapy. Active bleeding Past history of intracranial bleeding Ischemic stroke within 3 mo Recent neurosurgical or spinal procedure Head and craniofacial trauma Major surgery within 1 mo FIGURE 1 Incision placement for left and right pulmonary arteriotomy for surgical approach to acute PE. based interventions for massive and submassive pulmonary embolism remain suboptimal (see above). They are safe and feasible, but the therapeutic efficacy and freedom from chronic thromboembolic pulmonary hypertension remains low. Surgical pulmonary embolectomy is recommended for a massive and submassive pulmonary embolism with contraindications to thrombolytic therapy (Table 1). The list of typical indications for a surgical embolectomy is summarized in Table 2. Vanderbilt Classification simply divides pulmonary embolism into central (type A) and peripheral (type B) ones. This system is used by some centers to further determine the ideal candidacy for surgical embolectomy. 4,6 Patients with Vanderbilt Type A (clot in the main PA) pulmonary embolus are believed to be ideal candidates for surgery. When indicated, surgical pulmonary embolectomy is a well-established procedure that can be performed by the majority of cardiac surgeons. It is best done with the use of cardiopulmonary bypass using arterial cannulation and bicaval venous drainage. The patient remains normothermic and with the heart beating, avoiding cardiac arrest, unless there is a patent foramen ovale (PFO) or atrial septal defect (ASD) present. In the latter situations aortic cross clamping and cardioplegic arrest are necessary to avoid systemic air embolus and potential transfer of thrombus through the septal defect with subsequent systemic embolization. After initiation of a cardiopulmonary bypass, the main pulmonary artery is incised, with extension toward the left pulmonary artery (Figure 1, Arrow 1). This allows broad access to lobar and segmental branches of the left pulmonary artery. The embolus is typically readily visible and can be easily extracted with ring forceps. Gallstone forceps, normally used for an open common bile duct exploration, are a great additional tool allowing gentle grasping of the clots without fragmentation (Figure 4). They are also safe for the pulmonary artery intima. Open tip suction catheter allows extraction of smaller clots from segmental arteries. Additionally, massaging the lung from the outside with repeating Valsalva maneuvers, pushes small pieces of thrombus back into the larger branches of the pulmonary artery. TABLE 2 Indications for a surgical embolectomy. FIGURE 2 Incised right pulmonary artery with a suction catheter tip inside. Empty arrow: retracted ascending aorta; solid arrow: right pulmonary artery; empty arrowhead: venous drainage cannula in superior vena cava. Patient s head is toward the bottom of picture. Contraindications for thrombolysis Failure of thrombolytic therapy Failure of catheter therapy Clot in transit Large patent foramen ovale or atrial septal defect Active bleeding Severe right ventricular strain 46 JOURNAL OF THE MINNEAPOLIS HEART INSTITUTE FOUNDATION n Volume 2 n Issue 1 n Spring/Summer 2018

4 MUDY ET AL FIGURE 4 A fresh clot specimen retrieved from the left and right pulmonary artery tree. We have recreated the exact location of the individual clots on the back table as they were retrieved. FIGURE 3 Main pulmonary artery closed primarily with running 4-0 polypropylene suture (empty arrow). Solid arrow: right ventricular outflow tract; solid arrowhead: ascending aorta. Liberal use of heparinized saline in recommended during these maneuvers to wash out small fragments and the resulting clot sludge. After the left pulmonary artery embolectomy is completed, an additional separate incision in the right pulmonary artery is performed (Figure 1, Arrow 2). This is done after retracting the ascending aorta and superior vena cava in opposite directions (Figure 2). This approach provides excellent access to the whole length of the right pulmonary artery, lobar and segmental branches. The same maneuvers are applied to retrieve the thrombus burden from the right lung. Both incisions are primarily closed with a 4-0 polypropylene suture (Figure 3). Right ventricular recovery or at least improvement is typically immediately visible during and after separation from cardiopulmonary bypass. It is a common practice to place an inferior vena cava filter either in the operating room (delivered to infrarenal position in a retrograde fashion from the right atrium under fluoroscopic guidance) or immediately postoperatively. 15 Perioperative care of the embolectomy patient is standard for any cardiac surgery. Vasoactive drips and mechanical ventilation are weaned off as tolerated, but the right ventricular status must be closely monitored. The patient should be anticoagulated as soon as the chest tube drainage allows. surgery, and others to develop the current MHI algorithm for management of acute PE (Figure 5). When the patient is diagnosed with a massive pulmonary embolism and is hemodynamically unstable, an immediate conference call is initiated among the members of a multidisciplinary team, including the cardiothoracic surgeon on call. The clinical situation and imaging studies are reviewed, and the optimal management is chosen. Patients with a type A (central) massive embolism and no contraindications for surgery go to the operating room for embolectomy. In a situation of cardiovascular collapse, when there is no time for a transfer to the operating theater, venoarterial extracorporeal membrane oxygenation (ECMO) may be rapidly initiated. This way, hemodynamic stability is reestablished and further decisions may be made. If The Minnesota Heart Institute (MHI) Approach Based on the above indications and data and our experience between 2015 and 2017, we collaborated with the emergency department, cardiology, cardiac FIGURE 5 A preoperative computed tomography angiogram of the patient, from whom the clot on the previous picture was retrieved. JOURNAL OF THE MINNEAPOLIS HEART INSTITUTE FOUNDATION n Volume 2 n Issue 1 n Spring/Summer

5 SURGICAL PULMONARY EMBOLECTOMY FIGURE 6 The MHI multidisciplinary algorithm for acute pulmonary embolism. contraindications for surgery exist, anticoagulation with or without thrombolysis may be a treatment of choice, with the ECMO circuit remaining in place as long as mechanical circulatory support is necessary. For patients with a massive pulmonary embolism, for whom contraindications for surgery and thrombolysis exist, catheter-based therapy with a clot fragmentation and suctioning may be an option. Our experienced team of interventional radiologists is fluent in performing those procedures. Again, those patients can be supported with ECMO if hemodynamic instability requires. By applying this protocol, we hope to demonstrate improved outcomes for all patients with pulmonary embolism. TABLE 3 Operative characteristics and outcomes for patients operated on at Abbott Northwestern Hospital for PE. Age, y Indication for Surgery Contraindications for Systemic Thrombolysis Postoperative Complications LOS, d ICU Stay, d Mortality 1 58 Cardiogenic shock, ECMO, None Stroke (resolved), Prolonged air leak 37 8 No RV strain, central PE requiring blebectomy 2 77 RV strain, central PE Facial trauma Pneumonia 13 9 No 3 39 RV strain, clot in transit through PFO, central PE Uterine fibroids Postcardiotomy shock requiring V-A ECMO (5d), Postoperative bleeding with tamponade requiring reexploration No 4 58 RV strain, central PE History of multiple recent craniotomies for malignancy POD # 22 Ileus requiring reintubation for respiratory failure 11 6 No LOS, length of stay; PE, pulmonary embolism; ICU, intensive care unit; ECMO, extracorporeal membrane oxygenation; RV, right ventricular; PFO, patent foramen ovale 48 JOURNAL OF THE MINNEAPOLIS HEART INSTITUTE FOUNDATION n Volume 2 n Issue 1 n Spring/Summer 2018

6 MUDY ET AL FIGURE 6 Continued Between September 2015 and January 2017 there were 4 patients at Abbott Northwestern Hospital operated on for a massive PE with hemodynamic instability. The perioperative characteristics of the patients as well as the results are compiled in Table 3. All patients survived and were discharged home or to a rehabilitation facility. One patient suffered perioperative stroke that completely resolved within a few weeks. None of the patients suffered acute kidney injury requiring hemodialysis. All patients had a full recovery of right ventricular function. n Conclusion Surgical treatment provides good short- and long-term results for a subset of massive and submassive acute pulmonary embolism and offers the highest freedom from chronic residua. We hope that applying an organized, multidisciplinary algorithm will lead to quicker treatment application and improved outcomes for patients with acute PE. n REFERENCES 1. Dalen, JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis. 1975;17: Goldhaber SZ, Hennekens CH, Evans DA, Newton EC, Godleski JJ. Factors associated with correct antemortem diagnosis of major pulmonary embolism. Am J Med. 1982; 73: Rubinstein I, Murray D, Hoffstein V. Fatal pulmonary emboli in hospitalized patients. An autopsy study. Arch Intern Med. 1988;148: Neely RC, Byrne JG, Gosev I, et al. Surgical embolectomy for acute massive and submassive pulmonary embolism in a series of 115 patients. Ann Thorac Surg. 2015;100: Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease CHEST guideline and expert panel report. CHEST. 2016;149: Greelish JP, Leacche M, Solenkova NS, Ahmad RM, Byrne JG. Improved midterm outcomes for type A (central) pulmonary emboli treated surgically. JThoracCardiovascSurg. 2011;142: 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: Jaff MR, McMurtry MS, Archer SL, et al.; 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 JOURNAL OF THE MINNEAPOLIS HEART INSTITUTE FOUNDATION n Volume 2 n Issue 1 n Spring/Summer

7 SURGICAL PULMONARY EMBOLECTOMY chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123: Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; MOPETT Investigators. Moderate pulmonary embolism treated with thrombolysis (from the MOPETT Trial). Am J Cardiol. 2013;111: Kuo WT, Banerjee A, Kim PS, et al. Pulmonary embolism response to fragmentation, embolectomy, and catheter thrombolysis (PERFECT) initial results from a prospective multicenter registry. CHEST. 2015;148: Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014;129: AroraShilpkumar Lahewala S, Patel P, et al. Catheter-directed thrombolysis versus systemic thrombolysis in pulmonary embolism: predictors of in-hospital mortality and major bleeding. Circulation 2016;134(suppl 1):A Mattox KL, Feldtman RW, Beall AC Jr, DeBakey ME. Pulmonary embolectomy for acute massive pulmonary embolism. Ann Surg. 1982;195: Gulba DC, Schmid C, Borst HG, Lichtlen P, Dietz R, Luft FC. Medical compared with surgical treatment for massive pulmonary embolism. Lancet ;343: Muriel A, Jiménez D, Aujesky D, et al. Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk. JAm Coll Cardiol. 2014;63: JOURNAL OF THE MINNEAPOLIS HEART INSTITUTE FOUNDATION n Volume 2 n Issue 1 n Spring/Summer 2018

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