Massive and Submassive Pulmonary Embolism: Experience With an Algorithm for Catheter-Directed Mechanical Thrombectomy
Article Outline
Background
The role of catheter-directed mechanical thrombectomy (CDMT) for the treatment of massive pulmonary embolism (MPE) and submassive pulmonary embolism (SMPE) is not clearly defined. We report our experience with an algorithm for CDMT as a primary treatment in patients with MPE and SMPE.
Methods
We retrospectively reviewed our experience in treating MPE and SMPE in consecutive patients over a 2-year period (2008-2010). Patients with computed tomography angiography evidence of saddle, main branch, or ≥2 lobar pulmonary emboli in the setting of hypoxia, tachycardia, echocardiographic right heart strain, and/or cardiogenic shock underwent AngioJet CDMT, with or without adjunctive thrombolytic power-pulse spray. Outcomes, including angiographic success, clinical improvement, complications, and survival to discharge, were evaluated.
Results
Fifteen patients (8 men, 7 women; 14 SMPE, 1 SMPE) with a mean age of 59 years (range: 35-90 years) were treated for heart strain (100%), tachycardia (67%), hypoxia (67%), and cardiogenic shock (7%). Ten patients (67%) also received Alteplase power-pulse spray. Resolution of symptoms and improvement in heart strain were achieved in all patients. There were no in-hospital mortalities. Complications occurred in 3 patients (20%), including 2 patients with acute tubular necrosis and 1 patient with an intraoperative cardiac arrest. Average hospitalization was 9 days (range: 4-26 days). All patients were discharged on full anticoagulation. None required supplemental oxygen at discharge.
Conclusion
CDMT as primary treatment of MPE and SMPE has a high rate of technical and clinical success in a high-risk patient population. Experience and strict patient selection criteria may improve therapeutic outcomes.
Introduction
As the third leading cause of cardiovascular death in the United States, venous thromboembolism remains a common and lethal clinical entity.1, 2, 3 Acute symptomatic pulmonary embolism has an annual incidence greater than 500,000, with an estimated 30% mortality.2, 3 Despite current prophylactic measures and advancements in diagnostic modalities, the incidence of acute fatal pulmonary embolism among hospitalized patients has remained remarkably constant over the recent decades (10%-15%).3, 4, 5
The two most severe forms of acute pulmonary embolism are massive pulmonary embolism (MPE) and submassive pulmonary embolism (SMPE). MPE is defined as saddle, main branch, or ≥2 lobar pulmonary emboli, with associated cardiogenic shock. It carries an estimated 60% mortality, two-thirds of which occur within the first hour after onset.3, 5, 6 SMPE occurs in hemodynamically stable patients who demonstrate evidence of right heart strain, which is most commonly identified by echocardiography or by measurement of cardiac enzymes.3, 6 SMPE carries an estimated 15%-20% 30-day mortality rate, and has been associated with chronic thromboembolic pulmonary hypertension and subsequent cor pulmonale.7
Although systemic anticoagulation remains the cornerstone of therapy for acute symptomatic pulmonary embolism, the morbidity and mortality associated with MPE and SMPE warrant treatment beyond anticoagulation alone. More aggressive therapeutic options include systemic intravenous thrombolysis, surgical embolectomy, catheter-directed intra-arterial thrombolysis, and catheter-directed mechanical thrombectomy (CDMT). Despite major advancements in endovascular technology and growing experience internationally, the role of CDMT in treatment of acute pulmonary embolism remains inadequately defined.8, 9, 10 This is partially attributable to limited retrospective data, lack of large-scale randomized clinical trials, and the availability of various catheter-based devices, most of which are not approved by the United States Food and Drug Administration for treatment of pulmonary embolism.9, 10 As such, no standardized algorithm has been instituted for incorporation of CDMT into the acute pulmonary embolism treatment protocol. The goal of this study is to present a single center’s experience with such an algorithm using well-established criteria to evaluate outcomes.
Materials and Methods
We retrospectively reviewed our experience with CDMT of MPE and SMPE using the AngioJet rheolytic device (Possis, Minneapolis, MN) in consecutive patients over a 2-year period (2008-2010). Systemic thrombolysis was used neither before nor after our catheter-directed intervention. Outcomes were evaluated based on the resolution of shock, resolution of presenting symptoms, improvement in right heart strain, postinterventional complications, and in-hospital mortality.
Definitions
Shock was defined as systemic arterial hypotension (systolic blood pressure <90 mmHg, or >40 mmHg decrease from baseline) with clinical evidence of end-organ hypoperfusion (altered mental status, oliguria, lactic acidemia, etc.).8, 11 Shock resolution was achieved if hemodynamic stability (restoration of systolic blood pressure to >90 mmHG and/or <40 mmHg decrease from baseline without vasopressor support) was present in the absence of clinically evident end-organ hypoperfusion (including, but not limited to, creatinine and mentation at baseline levels, normal lactic acid levels). Right heart strain was defined as troponin level >0.01 ng/mL, or echocardiographic findings of right ventricular dilatation (right to left ventricular end-diastolic area ratio >1.0), right ventricular hypokinesis (McConnell’s sign), septal deviation, paradoxic septal motion, moderate to severe tricuspid regurgitation, or severe pulmonary hypertension (>40 mmHg).12, 13, 14
Algorithm
Figure 1 outlines our treatment algorithm. On clinical suspicion of an acute pulmonary embolism, patients underwent rapid risk stratification using various diagnostic modalities, including computed tomography angiography (CTA), transthoracic echocardiography (TTE), electrocardiography, troponin measurements, and duplex ultrasound of the lower extremities when indicated. In patients with a high clinical suspicion of a pulmonary embolism and a rapidly deteriorating clinical picture, once the diagnosis of MPE or SMPE was confirmed, no further diagnostic modalities were pursued because immediate intervention was the priority. When rapid clinical deterioration was not imminent, duplex ultrasound was obtained before CTA to verify the presence of a lower extremity deep vein thrombosis. If the clot burden was extensive (involving two or more named venous beds), or if the patient was deemed as a high-risk candidate for recurrent venous thromboembolism (bed-ridden or limited ambulation, perioperative status, history of past venous thromboembolism), an inferior vena cava (IVC) filter was placed immediately after the procedure. Patients without duplex ultrasound did not meet the aforementioned criteria and did not have any contraindication to anticoagulation. Therefore, anticoagulation alone was chosen as the treatment of choice in these patients following CDMT.
Fig. 1
Algorithm outline for CDMT as primary treatment for MPE and SMPE. CDMT, catheter-directed mechanical thrombectomy; MPE, massive pulmonary embolism; SMPE, submassive pulmonary embolism; CTA, computed tomography angiography; EKG, electrocardiography; TTE, transthoracic echocardiography; US, ultrasound (lower extremity); RHS, right heart strain; rt-PA, recombinant tissue plasminogen activator.
After the diagnosis of pulmonary embolism was established, complete anticoagulation (goal partial thromboplastin time: 60-90 seconds) was initiated and patients were categorized into two major groups. Those without shock or evidence of right heart strain were medically managed without any further intervention. Those with MPE or SMPE underwent further risk stratification based on their bleeding risk factors. Those with bleeding risks underwent CDMT alone, whereas those without bleeding risks underwent CDMT with adjunctive Alteplase (Genentech, San Francisco, CA) power-pulse spray during the same intervention. High-risk bleeding contraindications included patients with high risk for fall (includes those aged > 65 years with a history of previous fall, syncope or presyncope, stroke, or altered mental status), recent (<3 weeks) surgery or trauma, known intracranial disease, or any ongoing internal bleeding.
Technical Details
All interventions were performed either in the operating room equipped with a mobile C-arm device or in the catheterization suite. Percutaneous femoral venous access was achieved in all patients using a 6-French short sheath exchanged for a 7-French, 90-cm Shuttle sheath (Cook Medical, Bloomington, IN), which was then selectively placed over a 0.035-inch J-wire into the right and left pulmonary arteries. Systemic anticoagulation was resumed to maintain an activated clotting time ≥250 seconds. Prophylactic intravenous aminophylline was administered based on surgeons’ preference, so as to counteract the well described phenomenon of AngioJet-mediated bradycardia and hypotension. Bilateral pulmonary angiograms were performed through a 5-French pigtail catheter in both anteroposterior and ipsilateral oblique views. The 6-French Xpeedior (Possis, Minneapolis, MN) catheter was then advanced over a 0.035-inch stabilizer wire into the clot, where mechanical lysis was carried out. On the basis of, clinical picture, bleeding risks, and extent of embolic burden, adjunctive Alteplase power-pulse spray was administered through the same AngioJet catheter, with the exception that the aspiration port was turned off using a 3-way stopcock. Completion angiogram was then performed to evaluate the extent of clot lysis, which was graded as significant (> 75%), moderate (50%-75%), and minimal (< 50%). Adjunctive IVC filters were placed, as outlined earlier in the text.
Postinterventional Course
Patients were transferred to the intensive care unit for postoperative monitoring and were resumed on full anticoagulation. They were discharged from the hospital if they were asymptomatic with hemodynamic stability and had a therapeutic international normalized ratio.
Results
In general, 15 patients were treated, including 7 women. Mean age was 59 ± 16 years (range: 35-90 years). SMPE was identified in 14 patients (93%) and MPE in one (7%). All patients presented with saddle, main branch, or two or more lobar pulmonary emboli. Prophylactic aminophylline was administered in nine patients (60%), adjunctive Alteplase was administered in 10 (67%), and IVC filters were deployed in 10 (67%). A mean volume of 127 mL (range: 117-147 mL) of iodinated contrast was administered during CTA and CDMT. A mean dose of 29 mg of Alteplase (range: 20-37 mg) was administered during CDMT. Table I summarizes the demographic and clinical presentation of patients. Of note, right heart strain was identified in all patients. Among these, the most common finding was right ventricular dilatation (100%) and elevated troponins (87%).
Table I. Baseline demographic, clinical, and diagnostic data of all treated patients
| N = 15 | n (%) |
|---|---|
| Male | 8 (53) |
| Female | 7 (47) |
| Age (years) | 35-90 (mean 60 ± 16, median 59) |
| Risk factors | |
 Immobilization | 10 (67) |
| Recent surgery | 5 (33) |
| Malignancy | 4 (27) |
| Autoimmune/proinflammatory | 3 (20) |
| Recent trauma | 1 (7) |
| Coagulopathy | 1 (7) |
| Symptoms | |
| Dyspnea | 11 (73) |
| Chest pain | 7 (47) |
| Presyncope/syncope | 5 (33) |
| Palpitations | 2 (13) |
| Clinical presentation | |
| Submassive pulmonary embolus | 14 (93) |
| Massive pulmonary embolus | 1 (7) |
| Hypoxia | 10 (67) |
| Tachycardia | 10 (67) |
| Right heart strain | 15 (100) |
| Right ventricular dilatation | 15 (100) |
| Troponin I > 0.01 ng/mL | 13 (87) |
| Pulmonary hypertension | 7 (47) |
| Paradoxical septal motion | 7 (47) |
| Diagnostic modalities | |
| Computed tomography angiography | |
| Main branch embolus | 15 (100) |
| Saddle embolus | 11 (73) |
| ≥2 lobar emboli | 7 (47) |
| Lower extremity duplex ultrasound | |
| Lower extremity deep vein thrombosis | 10 (67) |
Completion angiogram demonstrated significant clot resolution in nine patients (67%), moderate in five (33%), and minimal in one (7%) (Fig. 2). Of those receiving adjunctive Alteplase,10 all had moderate to significant clot resolution. Of those not receiving Alteplase,5 only one (20%) had minimal clot resolution (Table II).
Fig. 2
(A) Pretreatment diagnostic angiography demonstrates marked decrease in right lung perfusion with obstructive embolus in right lower lobar pulmonary artery. (B) Posttreatment angiography shows marked improvement in right lung perfusion and lysis of previously noted embolus. Also demonstrated is the characteristic absence of flow at the periphery of the lung after AngioJet rheolysis. This is a transient phenomenon attributed to the microembolization of fragmented clot.
Table II. Extent of clot lysis with and without adjunctive local administration of tissue plasminogen activator (tPA) power-pulse spray
| Effect of adjunctive tPA on % clot resolution | > 50% | < 50% |
|---|---|---|
| + tPA (10) | 10 (100%) | 0 |
| − tPA (5) | 4 (80%) | 1 (20%) |
There were no clinically apparent in-hospital recurrences or in-hospital mortalities. At the time of discharge, resolution of symptoms was achieved in all patients. None required home oxygen therapy. All were discharged on full oral anticoagulation. Shock resolution was successfully achieved in the only patient with MPE. Postoperative TTE was obtained in 11 of 15 patients (73%). Of these, all demonstrated improvement or resolution of right heart strain. Of those presenting with elevated cardiac enzymes (13 patients; 87%), all demonstrated postinterventional normalization.
The overall complication rate was 3 in 15 (20%) patients. There were 2 minor (13%) cases of postinterventional acute renal failure (defined as serum creatinine ≥ 1.5 times baseline value or urine output < 0.5 mL/kg/hr) secondary to acute tubular necrosis in two hemodynamically stable patients without any preexisting renal disease. Peak serum creatinine levels were 2.9 and 3.9. These were managed conservatively with intravenous fluid resuscitation without the need for hemodialysis. There was 1 major (7%) case of intraprocedural cardiac arrest. This occurred in a 40-year-old woman with no history of cardiopulmonary disease. She presented with a large saddle embolus, severe right heart strain (troponin I: > 6 ng/mL; pulmonary artery pressure: > 60 mmHg), and presyncopal complaints, despite stable hemodynamics initially. She underwent CDMT with adjunctive thrombolysis under local anesthesia. Of note, she did not receive preprocedural aminophylline infusion. She became progressively hypoxic during the course of her treatment, requiring urgent intubation which led to cardiac arrest. Advanced cardiac life support was required for 30 seconds until successful regain of pulse was achieved. The case was aborted. Despite a prolonged course in the intensive care unit, she had an otherwise successful postprocedural recovery without any further complications. She was asymptomatic, with no evidence of right heart strain at discharge.
Discussion
The American College of Chest Physicians currently recommends catheter-based intervention only for those patients with MPE in whom systemic thrombolysis is contraindicated secondary to bleeding risks, or when sufficient time for intravenous infusion of the thrombolytic agent does not exist.8 However, multiple single-center series, as well as recent meta-analyses, have reported CDMT of acute symptomatic pulmonary embolism as a safe and effective modality, with favorable or comparable major complication rates relative to systemic thrombolysis.10 Furthermore, the growing awareness of chronic thromboembolic pulmonary hypertension as a serious complication of symptomatic pulmonary embolism has prompted some to advocate early catheter-based intervention for SMPE.7, 15, 16, 17, 18, 19, 20 These investigators propose that presence of right heart strain in the setting of acute pulmonary embolism, regardless of the hemodynamic status, is a risk factor for increased mortality, recurrence, and cor pulmonale that can be avoided if prompt catheter-based intervention is instituted in the symptomatic population.10
Given the limited clinical applicability, high hemorrhagic complication rates (≤ 25%), and controversial survival benefit of systemic thrombolysis, some debate exists as to whether CDMT should replace systemic thrombolysis in experienced centers as first-line treatment for acute symptomatic pulmonary embolism.21, 22, 23 It is important to point out that surgical embolectomy remains an important therapeutic option in treatment of acute pulmonary embolism. However, the relatively high morbidity and in-hospital mortality rates of approximately 30% have limited its utility as first-line treatment.3 CDMT has the theoretical advantage of both mechanical as well as biochemical clot lysis. As such, the thrombolytic dose can be minimized or possibly eliminated when mechanical fragmentation of the clot is sufficient to restore flow. Furthermore, it can be infused directly at the exposed surface of the fragmented clot without the need for systemic infusion, thereby minimizing the associated bleeding risk.
In the current experience with CDMT as primary therapy for MPE and SMPE, a high technical and clinical success rate was observed. This can be partially attributed to a relatively stable patient population, with only one case of MPE. This high success rate was present both with and without adjunctive thrombolysis. Furthermore, it did not appear that the addition of adjunctive thrombolysis during the procedure increased the risk of postprocedural mortality or hemorrhagic complications. It was also noted that the angiographic picture may not necessarily correlate with the extent of clinical improvement (Fig. 3).
Fig. 3
Extent of clot resolution did not appear to correlate with the clinical picture in this 59-year-old man. (A) Pretreatment computed tomography demonstrates large, saddle embolus with bilateral lobar arterial involvement. Although hemodynamically stable, severe right heart strain (pulmonary artery systolic pressure 60 mmHg; troponin I 0.6 ng/mL on presentation) was detected on pretreatment echocardiography. (B) Posttreatment computed tomography demonstrates resolution of saddle embolus but bilateral distal lobar emboli persist. Despite a suboptimal angiographic picture, this patient had an unremarkable postoperative course with rapid resolution of symptoms, and marked improvement in right heart strain over a 7-day length of stay (pulmonary artery pressure: <30 mmHg; troponin: < 0.012 ng/mL at discharge).
One possible explanation for this observation is that it is really the primary central bulk of clot that requires mechanical thrombectomy so that the patient experiences prompt clinical improvement. Therefore, any further attempts at achieving a higher percentage of clot resolution in the distal pulmonary vasculature may be an over-aggressive approach that can place the patient at an increased risk of perioperative complications. In our practice, we have used the clinical picture of the patient as our guide to length and extent of catheter-based intervention, and have placed only secondary emphasis on the anatomical picture. It has been our experience that improvement in oxygen saturation, tachypnea, tachycardia, and blood pressure is achieved as soon as the main bulk of clot is thrombectomized from the central pulmonary circulation. Once these clinical improvements are observed, we cease any further treatment even if the anatomical picture may still show significant residual clot. Therefore, based on our experience, the utility of catheter-directed thrombolysis during CDMT to achieve greater clot resolution remains questionable. It may best serve its role as an adjunctive measure if little or no clinical improvement is achieved in a timely manner by CDMT alone.
Despite the absence of periprocedural mortality, an overall 20% complication rate was encountered. In absence of shock, preexisting renal disease, and nephrotoxic pharmacotherapy, the two minor cases of transient renal insufficiency were attributed to a multifactorial process including a low-flow state and inadequate preoperative hydration exacerbated by contrast-induced nephropathy and AngioJet-mediated hemoglobinuria. To minimize such complications, we do not routinely obtain follow-up postprocedural CT scans, unless clinically indicated. Instead, we encourage the use of less invasive techniques such as TTE, cardiac enzyme trends, electrocardiography monitoring, and physical examination to gauge therapeutic success.
The case of the intraprocedural cardiac arrest was caused by several potential factors. The first was a severely compromised cardiac reserve signaled by TTE and cardiac biomarkers. Distal microembolization of fragmented clots may have contributed to the intraprocedural hypoxia, with further reduction in preload and worsening of right heart strain upon induction and intubation. Finally, the well-described phenomenon of AngioJet-mediated bradyarrhythmia and heart block must be considered. This entity has been reported in up to 15% of pulmonary embolectomy cases reported in the literature, with a higher incidence (24%-76%) in coronary interventions24, 25; however, the etiology remains controversial. The most popular theories to date include hemolysis and associated hyperkalemia and adenosine-mediated heart-block; intra-arterial and intraventricular stretch receptor-mediated reflex bradycardia; and hemolytic pulmonary vasoconstriction as a result of nitric oxide sequestration by the liberated hemoglobin.24, 25, 26, 27 Preoperative prophylaxis with methylxanthines, such as aminophylline, is advocated by those who attribute this phenomenon to the atrioventricular blocking property of the adenosine liberated during hemolysis. However, as demonstrated in this series, preoperative prophylaxis is not routinely used and requires further investigation before mainstream acceptance.24, 25, 26, 28 Future studies should focus on the incidence and treatment of this phenomenon, specifically during pulmonary embolectomy in both the MPE and SMPE subgroups. At present, we hold and recommend a low threshold for general endotracheal anesthesia for CDMT of MPE and SMPE so as to avoid the cardiovascular strain of urgent intubation during intervention, as was demonstrated by the aforementioned example.
The small size of the current series precludes us from advocating our algorithm as standard therapy for MPE and SMPE. Instead, we aimed to share an experience with a catheter-based algorithm that has demonstrated short-term technical and clinical success with an excellent safety profile perioperatively. Prospective, randomized trials are needed to compare these catheter-based interventions with more established treatment modalities, such as anticoagulation alone and systemic thrombolysis, before any stern recommendation can be made regarding a proposed therapeutic algorithm. We anticipate that growing awareness of this treatment option will prompt further investigation.
Conclusion
CDMT as primary treatment of MPE and SMPE is an effective and relatively safe tool, but does have its own unique set of complications. This requires large volume experience and awareness of potential technical pitfalls. Dedicated catheter technology and further clinical experience are needed for proper incorporation of protocols into randomized clinical trials for prospective comparison against some of the more established therapeutic options such as systemic thrombolysis and surgical embolectomy.
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PII: S0890-5096(11)00331-1
doi:10.1016/j.avsg.2011.05.026
Published by Elsevier Inc.
