Safety and Outcome of Rheolytic Thrombectomy for the Treatment of Acute Massive Pulmonary Embolism

Abstract: Background. Percutaneous rheolytic thrombectomy is an attractive alternative to thrombolytic therapy in patients with acute pulmonary embolism (PE), but its use is currently discouraged due to safety concerns. Methods. We studied 33 consecutive patients (age, 43 ± 13 years; 20 men and 13 women) with acute PE and contraindications to thrombolytic therapy who had rheolytic thrombectomy with the AngioJet catheter (Boston Scientific). Acute massive PE was initially diagnosed by computed tomography and then confirmed by pulmonary angiography. Pulmonary thrombus location was evaluated prior to the procedure. Anemia was defined as a decrease in hematocrit level <39% for men and <36% for women. Renal failure was defined as oliguria (urine output <500 mL/24 hours) or an increase in creatinine (>25% over baseline or an overall increase by 1 g/dL). Results. Catheter thrombectomy resulted in angiographic improvement in 32 patients (96%), with a rapid amelioration in functional class (from 3.3 ± 0.9 to 2.1 ± 0.7; P<.001) and an increase in oxygen saturation (from 71 ± 15% to 92 ± 17%; P<.001). No patient died. Side effects included transient heart block (n = 1), hypotension (n = 3), and bradycardia (n = 5). Anemia occurred in 4 patients, while renal failure was not detected. Clinical improvement was maintained during follow-up. At 1 year, systolic pulmonary pressure was significantly lower than at baseline (65 ± 31 mm Hg vs 31 ± 19 mm Hg; P<.001). Conclusions. Catheter thrombectomy with AngioJet in patients with acute massive PE and contraindications to thrombolysis is an effective therapeutic alternative that is not associated with relevant and persistent side effects, including the risk of death or developing anemia and renal failure.

J INVASIVE CARDIOL 2020;32(11):412-416. 

Key words: pulmonary embolism, rheolytic thrombectomy, thrombolysis

Acute, massive pulmonary embolism (PE) is a severe, life-threatening condition that requires prompt revascularization.¹ Current American and European guidelines state that the cornerstone for treatment of PE is pharmacologic therapy, including anticoagulation and systemic thrombolysis.^2-4 These treatments, however, suffer from several limitations, as they can be either unsuccessful or associated with a high bleeding burden. For this reason, percutaneous catheter-based approaches have been proposed as promising recanalization options.¹ However, experience with rheolytic thrombectomy in PE is limited to case studies or series, which have reported serious complications, such as profound bradyarrhythmia-induced hypotension, leading to hemodynamic collapse or death.^5,6 On the basis of available evidence, the United States Food and Drug Administration has issued a block-box warning that currently limits the use of the devices for rheolytic thrombectomy.¹ The aim of this study is to assess the safety and efficacy of rheolytic thrombectomy in a consecutive series of patients with acute massive PE and contraindications to thrombolytic therapy.

Methods

Study population. We evaluated consecutive patients with acute, massive PE and contraindications to thrombolytic therapy who were prospectively referred from “spoke” hospitals throughout the regional area of Lazio, Italy, to two central “hub” centers of the network located in Rome, Italy, to undergo urgent percutaneous rheolytic thrombectomy. All patients underwent pulmonary catheterization within 6 hours of diagnosis. Written informed consent was obtained from all patients. The study was approved by the institutional board review committees of the coordinating centers, as well as by local, regional authorities. 

Inclusion criteria were: (1) diagnosis of massive PE on the basis of clinical assessment, echocardiographic findings, and biomarkers according to the guidelines of the American Heart Association;² (2) evidence of extensive filling defects in either a main or proximal segmental pulmonary artery, as assessed by computed tomography at the spoke hospital and then confirmed by pulmonary angiography at the hub hospital; and (3) contraindications to use of thrombolytic therapy (both systemic and locally administered).³ Absolute contraindications included head trauma, brain surgery, and other major surgical procedures. Relative contraindications included traumatic and surgical injuries associated with a high risk of bleeding, as well as neurological pathologies that potentially could be exacerbated by bleeding. Exclusion criteria were: (1) evidence of subsegmental PE; (2) evidence of irreversible neurologic abnormalities; and (3) life expectancy of <6 months. Patients underwent thrombectomy irrespective of baseline pulmonary artery pressure.

Diagnostic and interventional procedures. All patients underwent a complete non-invasive diagnostic work-up at presentation, including clinical and biochemical assessment, and Doppler echocardiography.⁷ These examinations were newly obtained <24 hours after rheolytic thrombectomy and at 1-year follow-up visit. Pulmonary angiograms were performed before and after thrombectomy. According to our protocol, we administered 30 mL of dye in the pulmonary trunk and 10 mL of dye in the main pulmonary branches. In all cases, the Miller indexes before and after the procedure were calculated, as previously defined.⁸ Briefly, the Miller index was assessed as the sum of obstruction and perfusion indexes. The obstruction index was assessed on the basis of the presence of filling defects (1 point per segment) in any of 16 pulmonary artery branches (maximum score, 16). The perfusion index was scored on the basis of the flow in each pulmonary zone (maximum score, 18). The Miller index therefore ranged from zero (best) to 34 (worst).

Percutaneous rheolytic thrombectomy was performed 1-6 hours from the onset of PE symptoms. The femoral vein was cannulated with an 8 Fr introducer sheath. Hemodynamic parameters, including systolic blood pressure and systolic pulmonary arterial pressure, were measured before and during the procedure. First, a pigtail diagnostic catheter was positioned in the pulmonary trunk to perform pulmonary angiography in order to evaluate thrombus location. Then, thrombectomy was done with the AngioJet catheter (Boston Scientific), which creates thrombus aspiration force based on Venturi’s principle, and can aspire emboli from all occluded pulmonary branches. Multiple aspirations of the device (up to 10 seconds) in the occluded arteries were performed based on each patient’s tolerance. Thrombectomy was continued until clinical and/or angiographic improvement was shown. Clinical improvement was based on the evidence of hemodynamic stability (systolic blood pressure >90 mm Hg) and normalization of blood gas parameters (oxygen saturation >95%). Angiographic improvement was defined as the evidence of residual stenosis <30% of major pulmonary artery branches coupled with a good inflow to peripheral branches. 

Unfractionated heparin (UFH) according to current practice was immediately administered once the diagnosis of acute massive PE was suspected, unless absolute contraindications (ie, active bleeding) were present. In case of relative contraindications to anticoagulation (ie, recent trauma), low-molecular-weight heparin (LMWH) was used. During thrombectomy, UFH was administrated (intravenous bolus 70 IU/kg, followed by additional doses if needed in order to obtain an activated clotting time of 250-300 seconds), unless not absolutely contraindicated. After the procedure, anticoagulation with UFH or LMWH was continued in the intensive care unit. Patients were then switched to oral anticoagulants when they achieved hemodynamic stability.

Outcomes and follow-up. The primary endpoint of this study was the assessment of safety, ie, the frequency of complications of rheolytic thrombectomy. Along with mortality, specific attention was paid to the following complications: anemia, defined as a decrease in hematocrit level <39% for men and <36% for women, and renal failure, defined as oliguria (urine output <500 mL over 24 hours) or an increase in creatinine (>25% over baseline or an overall increase by 1 g/dL).⁹ Secondary endpoints of the study were the assessment of the acute and long-term effects of rheolytic thrombectomy, as assessed on the basis of clinical and hemodynamic features, blood gas parameters (pH and O2 saturation), and Doppler echocardiographic findings recorded before the procedure, <24 hours after the procedure, and at 12-month follow-up evaluation. 

Statistical analysis. Continuous data are presented as mean ± standard deviation and were compared by t-test or analysis of variance (if >2 groups). Categorical variables were expressed as number (percentage) and analyzed by the Chi-square test or Fisher’s exact test when appropriate. P-values <.05 (two-tailed) were considered significant. Statistical analyses were performed using SPSS, version 25.0 (SPSS). 

Results

Patient characteristics. Overall, 33 patients (20 men and 13 women) with PE were studied. Mean age was 43 ± 13 years. Assessment of comorbidities included smoking, diabetes, hypertension, and dyslipidemia (Table 1). The population showed several different risk factors for PE, including deep vein thrombosis, inherited or drug-induced thrombophilic disorders, recent surgery, or trauma (Table 1). Also, all patients had an absolute or relative contraindication to fibrinolysis, including active bleeding, malignancy, and recent surgery or trauma (Table 1). Of note, 1 patient had a suicide attempt with 20 pills of gestodene 60 µg/etinylestradiol 15 µg plus 20 pills of valproic acid. 

Pulmonary angiography performed prior to thrombectomy revealed an occlusion of both pulmonary arteries in 5 patients, occlusion of 3 lobar arteries in 12 patients, occlusion of 4 lobar arteries in 14 patients, and occlusion of 5 lobar arteries in 2 patients. Total volume of contrast dye administered was 72 ± 26 mL (range, 45-135 mL). No patient experienced hemodynamic changes due to injection of contrast dye. Catheter thrombectomy resulted in immediate angiographic improvement in all patients except 1 (Figure 1), in whom pulmonary angiography after the procedure was unchanged as compared with preinterventional angiogram. Miller index was significantly decreased after the procedure as compared with baseline values (12.5 ± 4.5 vs 20.9 ± 5.7, respectively; P=.01). 

At time of diagnosis, 20 patients received UFH and 6 patients received LMWH, whereas 7 patients were not given anticoagulation due to absolute contraindications (active bleeding in 5 patients and recent trauma in 2 patients). Periprocedural anticoagulation with UFH was given to all but the 5 patients with active bleeding (4 of them were on oral anticoagulants). After the procedure, UFH or LMWH was administered to all patients depending on clinical conditions.

Primary endpoints. The use of AngioJet was feasible in all patients, and was not associated with major complications. Specifically, no patient died during the procedure or during the following hospital stay. Periprocedural side effects included transient heart block (1 patient), hypotension (3 patients), and bradycardia (5 patients). Of note, there were no serious adverse events directly associated with AngioJet, such as major bleeding, distal embolization, or perforation of the pulmonary arteries. After the procedure, anemia was detected in 4 patients, while no patient had evidence of developed renal failure.

Secondary endpoints. Rheolytic thrombectomy was associated with significant changes in clinical features, biochemical parameters, and Doppler echocardiographic findings (secondary endpoints). Before the procedure, all patients were in functional class 3 or 4, and had a heart rate >100 beats/min, a systolic blood pressure <90 mm Hg, and an oxygen saturation <95% (Table 2). Also, echocardiography demonstrated right ventricular overload associated with an increase in peak systolic pulmonary artery pressure over the upper limits of normal in the majority of patients (Table 2). After the procedure, there was a rapid amelioration in functional class, heart rate, systolic blood pressure, pH, and oxygen saturation. Also, postprocedural Doppler echocardiography disclosed a slight, but significant, decrease in indexes of right ventricular overload and pulmonary artery pressure. A complete 12-month follow-up assessment was done in 30 of the 33 patients (91%). Most of them showed normal clinical conditions, normal biochemical parameters, and evidence of a persistently normal right ventricular size and function, with a decrease to normal of the peak systolic pulmonary pressure (Table 2). 

Discussion

The results of our study show the following: (1) catheter thrombectomy with AngioJet is feasible and effective in patients with acute massive PE and contraindications to thrombolysis; (2) rheolytic thrombectomy is not associated with relevant and persistent side effects, including the risk of death or developing anemia and renal failure; and (3) the procedure is associated with long-standing clinical and functional benefits.

Since the 2000s, rheolytic thrombectomy has been proposed as an alternative to pharmacologic strategies for the treatment of acute PE.^10-16 The rationale of the technique lies in the fact that mechanical fragmentation of pulmonary emboli has the potential to increase the chance of recanalization of the pulmonary artery as compared with pharmacologic treatments. Indeed, several case report and small studies have shown that rheolytic thrombectomy in high-risk patients with PE can be safe and effective, and that the risk of serious adverse events compares favorably with anticoagulation or fibrinolytic therapies.^10-16 

The overall positive findings described in anecdotal experiences, however, have been shadowed by a few cases of severe procedural-related complications and deaths.^5,6 As a consequence, current scientific guidelines do not support the use of rheolytic thrombectomy in high-risk patients with PE. The American College of Chest Physicians recommends an endovascular intervention only in patients with contraindications to fibrinolysis, primarily those with a high risk of bleeding.³ Similarly, the European Society of Cardiology suggests the endovascular approach as an alternative for surgical embolectomy in patients in whom thrombolysis has failed (class IIa; level of evidence C).⁴ Recently, the United States Food and Drug Administration has issued a black box warning on the device label,¹ warning that, based on safety concerns, the AngioJet device should not be used as the initial treatment in patients with acute PE.

This study details one of the largest experiences of patients with acute, massive PE and absolute contraindications to pharmacologic treatments who underwent urgent rheolytic thrombectomy. In this high-risk subset of patients, the treatment objective was to accelerate thrombus dissolution and achieve rapid reperfusion of the pulmonary arteries. The catheter-directed intervention resulted in hemodynamic improvement with restoration of right ventricular function, normalization of right ventricular size, and reduction of abnormally high pulmonary arterial pressures. 

The major result of our study is that rheolytic thrombectomy was not associated with major, life-threatening complications, as no patient died or experienced major bleedings. Review of the literature shows that potential complications associated with the use of percutaneous thrombectomy are profound bradyarrhythmia, hypotension, renal impairment, hemoptysis, and major and minor hemorrhages.¹⁷ Bradyarrhythmia and hypotention can be caused by the release of neurohormonal substances, such as adenosine and bradykinin associated with the concomitant activation of stretch receptors in the pulmonary arteries. Hemolysis and hemoglobinuria may contribute to the development of acute oliguric renal failure. Also, hyperkalemia may trigger electrical instability, thus leading to severe ventricular arrhythmias. Progressive anemia can result from vascular complications in the access sites and/or from comorbidities determining an increased risk of bleeding, such as malignancy.¹⁷  

A novel finding of our study is that rheolytic thrombectomy was associated with the maintenance of long-term clinical and functional benefits, thus confirming and expanding observations from recently published case series.^18-21 These newer results underline the fact that, at experienced centers, the use of modern mechanical approaches can be either life saving in cases of acute massive PE, or be associated with long-standing amelioration of pulmonary and right-sided heart functions.

Study limitations. A number of limitations should be acknowledged. Our experience is limited by the small sample size and heterogeneity of the patients who had different risk factors for PE and different contraindications to thrombolysis. A further limitation is constituted by the lack of a control group. As a consequence, our findings might not apply in the subset of patients with clinical characteristics different from our study population. Most importantly, patients were not randomized to different therapeutic strategies. However, only a randomized clinical trial design may be able to reliably demonstrate a significant effect of any given procedure.

Conclusion

Our study shows that catheter thrombectomy with AngioJet in patients with acute massive PE and contraindications to thrombolysis is an effective therapeutic alternative that is not associated with relevant and persistent side effects, including the risks of death, developing anemia, and renal failure.

From ¹the Department of Cardiovascular Sciences, Sapienza University, Rome, Italy; and ²Interventional Cardiology Unit, San Filippo Neri Hospital, Rome, Italy. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

The authors report that patient consent was provided for publication of the images used herein.

Manuscript accepted April 21, 2020.

Address for correspondence: Francesco Pelliccia, MD, PhD, FACC, Department of Cardiovascular Sciences, Sapienza University, Viale del Policlinico 155, 00166 Rome, Italy. Email: f.pelliccia@mclink.it

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