Use of the STEMI Team for Treatment of Patients With Pulmonary Embolism: A Pilot Study

Abstract: Background. Patients with massive and submassive pulmonary embolism (PE) require rapid identification, triage, and consideration for reperfusion therapy. Use of an existing ST-segment elevation myocardial infarction (STEMI) team and activation protocol may be an effective means to care for these patients. Objective. The objective of this analysis was to evaluate a pilot study using the STEMI team and a dedicated PE protocol for treatment of patients with massive and submassive PE. Methods. From June 2014 to April 2016, a total of 40 patients with massive and submassive PE were evaluated. Baseline demographics, mode of hospital entry (transfer-in, in-hospital, and emergency department [ED] arrival), treatment time intervals (door to computed tomography PE protocol [CTPE], CTPE to invasive pulmonary angiogram, door to treatment time), procedures performed, and in-hospital clinical events were collected. Results. Mean age was 56 ± 14 years, 17 (42%) were male, and 12 (30%) had a prior history of deep venous thrombosis or PE. Twenty-three patients (57%) had massive PE and 17 patients (43%) had submassive PE. Mode of hospital entry was transfer-in (38%), in-hospital (20%), and ED arrival (42%). Four patients (10%) presented with cardiac arrest, 8 patients (20%) required intubation, and 5 patients (12%) required extracorporeal membrane oxygenation. Ten patients (25%) received anticoagulation therapy or placement of inferior vena cava filter, 3 patients (7.5%) received diagnostic pulmonary angiography alone, and 27 patients (67.5%) received endovascular treatment. For patients arriving via the ED, door to CTPE was 4.9 ± 3.6 hours, CTPE to diagnostic pulmonary angiography was 7.8 ± 8.5 hours, and door to treatment time was 10.2 ± 9.0 hours. Endovascular devices utilized included combinations of rheolytic and other thrombectomy devices as well as catheter-directed fibrinolysis. Length of hospital stay was 15 ± 15 days and in-hospital survival rate was 90%. Conclusions. Use of an existing STEMI team and activation protocol is a feasible method to care for patients with massive and submassive PE. This pilot study demonstrated rapid treatment times with low in-hospital mortality.   

Reprinted with permission from J INVASIVE CARDIOL 2018;30(10):367-371.

Key words: catheter-directed thrombolytic therapy, percutaneous mechanical thrombectomy, pulmonary embolism, pulmonary embolism response team

Acute pulmonary embolism (PE) affects an estimated 900,000 individuals annually in the United States and results in approximately 150,000 deaths.¹ The mortality rate for massive PE is high, approaching 50% at 3 months, with the majority of deaths occurring within the initial hours of presentation.^2-4 Although systemic thrombolysis is highly effective, limitations include major bleeding, intracerebral hemorrhage, and contraindications in approximately 60% of patients.^5,6 In recent years, catheter-directed therapy has emerged as an alternative to systemic thrombolysis.^7,8

The ability of the cardiac catheterization laboratory (CCL) team to rapidly triage and initiate therapy has improved the care of patients with ST-segment elevation myocardial infarction (STEMI) and out-of-hospital cardiac arrest and has recently been proposed as a means to provide prompt neurovascular intervention for treatment of acute stroke.^9-12 The concept of a PE response team (PERT) was developed by a multidisciplinary group at Massachusetts General Hospital in 2014 and applies the principles of early diagnosis, protocol-based care, and use of endovascular therapy for those with massive PE.^13-16

The objective of the current study was to evaluate our initial experience using the CCL team to respond to patients with an acute PE using a dedicated Code PE protocol. We sought to evaluate treatment times for patients presenting via the emergency department (ED) and evaluate short-term clinical outcomes.

Methods

Patient population. From June 2014 to January 2017, a total of 40 patients with massive and submassive PE were evaluated. This study was approved by a waiver of informed consent by the Institutional Review Board. Patients were treated at Keck Hospital of USC and Los Angeles County USC Medical Center. Referring physicians and ED physicians were given multiple in-service presentations regarding the indications and mechanism to activate the CCL team for a Code PE. The Code PE protocol mandated rapid identification of patients with massive and submassive PE and currently does not include patients with low-risk PE (normal blood pressure and no evidence of right ventricular dysfunction). For hemodynamically stable patients, imaging with computed tomography with PE (CTPE) protocol was recommended prior to CCL activation. For hemodynamically unstable patients who were deemed too unstable to undergo CTPE, the diagnosis of massive PE was made based upon bedside transthoracic echocardiography and clinical presentation. Massive PE was defined as hemodynamic instability with systolic blood pressure <90 mm Hg or requiring inotropic support to maintain systolic blood pressure >90 mm Hg. Submassive PE was defined as systolic blood pressure >90 mm Hg with right heart dysfunction including a dilated right ventricle (by echocardiography or CTPE) or elevated basic natriuretic peptide (BNP, >90 pg/mL) or troponin T (>0.1 ng/mL) levels. A dilated right ventricle by echocardiography was defined as visually assessed increase in right ventricular chamber size. A dilated right ventricle by CTPE was defined as right ventricle/left ventricle ratio of ≥0.9. Mode of hospital entry was classified as “transfer-in” if the patient was transferred from an outside hospital, “in-hospital” if PE occurred during the index hospitalization, and “ED arrival” if the patient presented via walk-in or emergency medical services transport to the ED.

Code PE protocol. A multidisciplinary team including physicians from the ED, critical care medicine, and interventional cardiology was established with the goal of instituting a Code PE protocol. The aim of the Code PE protocol was to: (1) rapidly identify patients with massive and submassive PE; and (2) triage appropriate patients directly to the CCL for endovascular treatment. The Code PE protocol was instituted using an existing CCL activation protocol that uses physician group paging by the ED physician for patients with STEMI and/or out-of-hospital cardiac arrest. For patients with massive and submassive PE at an outside hospital and those currently hospitalized, the CCL team is activated via the referring physician contacting the on-call interventional cardiologist, who then activates the group paging system.

Procedures and treatment received. Activation of the CCL via Code PE protocol results in immediate assessment by the on-call interventional cardiologist, rapid interpretation of the CTPE, and subsequent transfer to the CCL for pulmonary angiography and consideration of endovascular intervention. For patients with refractory hypotension, extracorporeal membrane oxygenation (ECMO) with either CardioHELP (Maquet) or CentriMag (Thoratec) was initiated in the CCL. Based upon treatment received, patients were classified into the following groups: (1) anticoagulation therapy with or without placement of inferior vena cava filter; (2) diagnostic pulmonary angiography only; or (3) endovascular intervention. All patients receiving endovascular intervention underwent diagnostic pulmonary angiography and received anticoagulation. Endovascular intervention was performed at the discretion of the attending interventional cardiologist and thus could include a number of devices and treatment approaches. Endovascular therapy was classified as rheolytic thrombectomy (Angiojet; Boston Scientific), other thrombectomy device (Penumbra; Penumbra, Inc.), mechanical thrombectomy or maceration with rotating pigtail catheter (EkoSonic endovascular system; EKOS), and continuous catheter-directed pulmonary artery infusion of tissue plasminogen activator (tPA). Intravenous heparin was given during the procedure and continued following the procedure with a target activated partial thromboplastin time of 40-60 seconds. Manual hemostasis was used for venous sheath removal at the access site. Full therapeutic anticoagulation was restarted 30 minutes after hemostasis was achieved.

Study variables. The efficiency of the Code PE protocol was assessed using treatment time intervals for patients presenting via the ED. Treatment time intervals included door to CTPE, CTPE to diagnostic pulmonary angiography, and door to treatment. Treatment time was defined as the time of placement of any endovascular therapy device within the pulmonary vasculature. In-hospital clinical events included length of hospital stay, bleeding events, blood transfusion, and survival to hospital discharge. Bleeding events were classified as intracerebral hemorrhage, hematoma >10 cm, loss of distal pulses, and/or the need for endovascular or surgical treatment to control access-site or vascular bleeding.

Statistical analyses. Categorical variables are presented as number and percentage. Continuous variables are presented as mean ± standard deviation. Student’s t-test was used to compare continuous variables and Chi-square or Fisher’s exact tests were used to compare categorical variables. A P-value <.05 was considered statistically significant.

Results

Baseline characteristics. Mean age was 56 ± 14 years, 45% were male, and 30% had a prior history of PE or deep venous thrombosis (Table 1). Risk factors for PE included active malignancy in 25%, receiving chemotherapy in 18%, recent surgery or immobilization in 30%, and hormone or oral contraceptive pill use in 13%. Systolic blood pressure was <90 mm Hg in 45%, 10% presented with cardiac arrest, and 20% required endotracheal intubation. ECMO was used in 12% for refractory hypotension.

Treatment time intervals. For patients presenting via the ED, door to CTPE was 4.9 ± 3.6 hours, CTPE to diagnostic pulmonary angiography was 7.8 ± 8.5 hours, and door to treatment time was 10.2 ± 9.0 hours (Figure 1).   

Treatment received. Ten patients (25%) received anticoagulation therapy or placement of an inferior vena case filter, 3 (7.5%) received diagnostic pulmonary angiography alone, and 27 (67.5%) received endovascular intervention (Table 2).  Reasons for use of anticoagulation alone or performance of diagnostic pulmonary angiography without endovascular intervention included patient refusal, absolute contraindications to anticoagulation, and improvement in clinical status such that endovascular therapy was not deemed necessary.  Placement of an inferior vena cava filter was considered in patients with absolute contraindications to anticoagulation.  For patients receiving endovascular intervention, a number of endovascular devices were utilized (Table 2). The most common endovascular devices were various combinations of rheolytic and other thrombectomy devices and catheter-directed fibrinolytics. Catheter-directed fibrinolytics used a continuous infusion of tPA post procedure via an infusion catheter with an average total treatment dose of 30 ± 17 mg.

Clinical events. Length of hospital stay was 15 ± 15 days (Table 3). Bleeding events occurred in 12.5% and a blood transfusion was required in 15%. There were no fatal bleeding events and no intracranial hemorrhages. Overall survival to hospital discharge was 90%. Approximately one-half of patients who survived to hospital discharge were discharged to home.

Discussion

In the current study, we evaluated the use of the CCL team to respond to patients with massive and submassive PE using a dedicated code PE protocol and group paging system. We found rapid treatment times for those patients presenting via the ED and high in-hospital survival. These preliminary findings suggest that the CCL team can be effectively used to care for these patients.

Treatment goals for patients with massive and submassive PE include rapid identification, quantification of right ventricular dysfunction, initiation of anticoagulation, and consideration of advanced endovascular therapy to ameliorate the extensive thrombus burden within the pulmonary vasculature. Although thrombolytic therapy had been the mainstay of therapy for patients with massive PE, contraindications and subsequent bleeding complications limit their utility.^5,6,17,18 Catheter-directed therapy, however, significantly reduces the overall thrombolytic agent dose by allowing direct administration to the pulmonary vasculature and therefore may be a more effective treatment option. The recently completed SEATTLE II (Prospective, Single-arm, Multi-center Trial of EkoSonic Endovascular System and Activase for Treatment of Acute Pulmonary Embolism) study included 150 patients with massive and submassive PE and used a mean total tPA dose of 23.7 ± 2.9 mg delivered directly to the pulmonary vasculature via an ultrasound-facilitated lytic infusion catheter.⁷ The primary safety outcome of major bleeding within 30 days occurred in 15 patients (10%), with no patients experiencing intracranial hemorrhage. The primary efficacy outcome of the mean change in CT-measured right ventricular to left ventricular diameter ratio was significantly reduced after catheter-directed lysis  (-0.42; P<.001). Mean pulmonary artery systolic pressures also decreased significantly, from 51.4 mm Hg at baseline to 36.9 mm Hg post procedure (P<.001).

The PERFECT (Pulmonary Embolism Response to Fragmentation, Embolectomy and Catheter Thrombolysis) registry also provides contemporary data regarding treatment approaches and outcomes of patients with acute PE.¹⁹ A total of 101 patients with massive (28%) and submassive PE (72%) were included from seven clinical sites over a 3-year period. The majority of patients received catheter-directed thrombolysis using either ultrasound-assisted thrombolysis or a standard infusion catheter with either tPA (mean total dose 28 ± 11 mg) or urokinase. There were no major bleeding events at 30 days, and the in-hospital survival rate was 94%.

In the current study, we chose to characterize treatment times for patients arriving via the ED in a manner similar to that used for STEMI patients. We analyzed door to CTPE, CTPE to diagnostic pulmonary angiography, and door to treatment times in order to assess timeliness of therapy. To our knowledge, such intervals for patients with massive and submassive PE have not been previously reported. Optimal treatment intervals thus remain to be established. In this analysis, we only included patients arriving via the ED to avoid confounding issues related to patients requiring inter-facility transfer and those who developed PE while in-hospital; these groups represent additional logistic challenges for timely evaluation and treatment.

The initial experience of the Massachusetts General Hospital PERT was recently published.¹⁴ During a 30-month period, there were 394 PERT activations for confirmed PE, with 28% categorized as low-risk PE, 46% as submassive PE, and 26% as massive PE. Systemic or catheter-directed thrombolysis was used in 35 patients (11% of the entire cohort). Thirty-day mortality rate for the entire cohort was 12%, but was 25% for those with massive PE. Our current series differs in that we only included patients with submassive or massive PE. In addition, a higher proportion of our cohort received endovascular therapy, and only short-term, in-hospital survival is reported.

Although all patients included in the current series had massive and submassive PE, only 67.5% ultimately underwent some form of endovascular treatment. This was related to a significant number of patients experiencing an improvement in clinical status, such that endovascular therapy was deferred. In addition, there were several patients who had absolute contraindications to the anticoagulation required for endovascular intervention; these patients received inferior vena cava filter placement only.

Study limitations. There are several limitations of the present analysis. Our cohort included a relatively small number of patients treated within a single hospital system. The applicability of these results to other STEMI treatment centers remains unclear. The endovascular approach to treatment was not standardized and included multiple combinations of various endovascular devices, both with and without fibrinolytic therapy. This variability may have influenced the observed outcomes. In addition, patients at outside facilities who were evaluated for transfer but died prior to transfer or died during transfer were not included in the analysis. Exclusion of such critically ill patients likely results in selection bias. Lastly, only short-term clinical outcomes were available.

Conclusion

There is a growing trend for standardized activation methods and protocols for the treatment of cardiovascular emergencies including STEMI, out-of-hospital cardiac arrest, and stroke. Use of an existing STEMI team and dedicated PE protocol may be an effective means to care for patients with massive and submassive PE. 

From the ¹Division of Cardiovascular Medicine, University of Southern California, Los Angeles, California; and ²Department of Emergency Medicine, University of Southern California, Los Angeles, California.

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.

Manuscript submitted May 27, 2018, provisional acceptance given June 4, 2018, final version accepted June 18, 2018.

Address for correspondence: David M. Shavelle, MD, Division of Cardiovascular Medicine, University of Southern California, 1510 San Pablo Street, Suite 322, Los Angeles, CA 90033. Email: shavelle@usc.edu

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