Interviews with ISET Abstract Authors

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Submitted on Sun, 06/24/2018 - 12:23
Citation
VASCULAR DISEASE MANAGEMENT 2018;15(6):E56-E59.

Submassive and Massive Pulmonary Embolus: Catheter-Directed Intervention Versus Medical Management?

Abstract Authors: C.T. Hennemeyer, G.J. Woodhead, A.H. Shah, S. Sakla, C.Q. Moffett, S. Black

Hennemeyer and Woodhead

Interview with Charles T. Hennemeyer, MD, and Gregory J. Woodhead, MD, PhD

VDM: Why did you choose to pursue research in this area, and what sets your study on catheter-based therapies apart from what is already in the literature?

Drs Hennemeyer and Woodhead: Multiple new/novel catheter-based devices have appeared over the last 18 months that allow for more elegant and effective management of submassive/massive pulmonary embolism (PE). We chose to investigate the combination of several new catheter-based technologies, used in combination rather than separately, for the treatment of submassive PE. Perhaps the combination of mechanical aspiration with or without lysis could yield better results than either one alone. Based on early results, we were soon encouraged by what we found and began collecting data.

VDM: Can you briefly describe your findings?

Drs Hennemeyer and Woodhead: One of our primary endpoint measurement tools was pre- and postprocedural right ventricular to left ventricular ratio (RV/LV ratio) measurements on echocardiography, computed tomography angiogram, and in some cases magnetic resonance angiogram. We compared the catheter intervention group against controls who received standard-of-care intravenous heparin alone. We found a significant improvement in preprocedural RV/LV ratios in the catheter-based group. Most patients received a 30-mg tissue plasminogen activator bolus followed by mechanical clot aspiration, and approximately one-third received additional overnight catheter-based lysis.

VDM: Tell me about something surprising you encountered while doing this research.

Drs Hennemeyer and Woodhead: We were surprised by the magnitude of improvement achieved using combination technology, even when the angiographic endpoint was less than complete clot removal. In fact, most cases demonstrated at least some angiographically visible residual clot, yet outcome measures seemed disproportionately positive. This suggests that even with imperfect tools, relatively small gains in clot removal result in large gains in right heart strain. 

VDM: How might your findings eventually affect clinical practice?

Drs Hennemeyer and Woodhead: We believe that interventional radiology (IR)-directed catheter thrombolysis of PE is poised for a cardiac catheter moment. Our future research endeavors will focus on how catheter-based interventions affect long-term functional outcomes such as pulmonary vascular reserve and pulmonary exercise tolerance. We believe that if a significant deviation from the natural history can be achieved, catheter-based interventions in the future may become the standard of care, analogous to other common clinical cardiac practices such as coronary angioplasty and stenting.

VDM: What future studies would you like to see take place? 

Drs Hennemeyer and Woodhead: First, after a thorough review of the literature, it is clear that there is not a good measure of right heart dysfunction, especially when it comes to determining which patients with PE stand to benefit the most from catheter-directed interventions. The echocardiography value, TAPSE, has shown some promise, but it remains a qualitative measure. Systolic pulmonary artery pressures are highly variable, and RV/LV ratios are also prone to measurement error/variability. Therefore, development of a new gold-standard measurement of right heart dysfunction in the setting of PE is of the utmost importance. Second, while our study was retrospective in design, we are currently enrolling patients in a prospective, randomized controlled trial in order to validate our observations/conclusions.

VDM: What are you hoping that attendees take away from your presentation?

Drs Hennemeyer and Woodhead: Catheter-based pulmonary intervention with additional tools beyond simple lytic devices may offer long-term benefits to patients with PE commonly treated with heparin alone. We hope that other IR practices will continue to experiment with combinations of multiple devices and protocols to achieve better results. However, we would encourage our fellow IRs to experiment with combining catheter-based devices/therapeutics in order to achieve superior results over standard medical management. 

Abstract

Purpose: To use retrospective analysis of right heart strain measures before and after catheter-directed intervention in massive and submassive pulmonary embolus (PE) and compare outcomes with matched control participants New tools for catheter intervention allow for combination mechanical and chemical lytic therapy for massive and submassive PE. The authors hypothesize that when used in combination, clot aspiration devices and catheter-directed lytics substantially improve measures of right heart strain compared with standard medical management. Furthermore, timely catheter-based intervention on massive and submassive PE may provide a foundation for altering the course of pulmonary thromboembolic disease. 

Materials and Methods: A retrospective study was approved by the institutional review board to investigate patient outcomes after catheter-based therapies comparing them with control participants. In the treatment group were 25 patients who underwent catheter-based therapy consisting of single or combination mechanical and chemical lytic therapy. A control group of 25 patients who were diagnosed with PE during the same time period was matched for relative clot burden, similar severity of disease (right ventricular–to–left ventricular [RV-to-LV] ratios), age, preexisting chronic obstructive pulmonary disease, and other pertinent risk factors. Control patients received standard of care medical management, including systemic anticoagulation only. All available pre- and postprocedural cardiac imaging, including CTA, and echocardiography were gathered and used to assess RV-to-LV ratios, as an indirect measure of right ventricular strain. Two blinded, fellowship-trained cardiothoracic imaging physicians (each with greater than 7 years of experience) evaluated the pre- and posttreatment computed tomography angiography (CTA) and echocardiography images. These blinded physicians acquired RV-to-LV measurements from diagnostic CTA and echocardiographic images at all time points according to established methods. Measurements of RV and LV diameters pre- and posttherapy, as well as assessment of clot burden and location were recorded in an anonymized data table.  

Results: Over a period of approximately 1 year, 25 patients at a single institution underwent catheter-based thrombolysis of submassive and massive PE. Two devices were used, either alone or in combination: (1) Indigo Mechanical Thrombectomy System (Penumbra, Alameda, CA) and (2) EKOS Acoustic Pulse Thrombolysis (BTG, London, United Kingdom). The total dose of administered tissue plasminogen activator was roughly uniform in both catheter-directed treatment groups, averaging 28 mg, and was administered either as a single bolus or as 12- to 24-hour infusion (average, 22 hours). Average preprocedure diagnosis was 1 day. Postprocedure imaging was performed at 48 hours after the initiation of medical management and systemic anticoagulation or after IR catheter-directed therapy (average postprocedure follow-up time-point, 1.8 days). Measurements of RV-to-LV ratios between the catheter-directed thrombolysis and medical management groups before and after therapy demonstrated a statistically significant reduction in RV strain, as measured by a change in RV-to-LV ratio. Specifically, the catheter-based group demonstrated an improvement in average RV-to-LV ratio of 25% at 48 hours (P < 0.05) versus the medical management group, which showed a slight average increase in this ratio (7%; P <0.1). No adverse events were reported in either group.   

Conclusions: Catheter-based management of massive and submassive PE shows improved RV-to-LV ratio, an indirect measurement of right heart strain, compared with medical management alone. A combination of widely available catheter-based devices, either mechanical aspiration or ultrasound-enhanced thrombolysis may be used in management of intermediate- and high-risk PE patients safely. If widely available, catheter-based therapy stands also to change the practices of interventional radiology physicians. The importance of catheter treatment could approach that of other cardiac emergencies such as ST elevation myocardial infarction, creating the expectation to provide emergent or semi-emergent response. Although RV-to-LV ratios are a useful and a widely available indicator of short-term right heart strain, better measures of cardiac strain and total pulmonary vascular reserve are needed to more precisely measure the long-term impact of invasive therapy and to understand the impact on disease progression to chronic pulmonary hypertension.

 

Abstract Authors: R. Saxon, J.F. Benenati, C. Teigen, L. Sewall, G.L. Adams

Interview with Richard Saxon, MD

VDM: What sets your study apart from what is already in the literature?

Dr Saxon: When compared with research on the treatment of critical limb ischemia, there is relatively little research being done on the endovascular treatment of acute and subacute limb ischemia caused by arterial thromboembolism. PRISM, the first attempt at a multicenter, objective evaluation of the XTRACT technique, used the Penumbra/Indigo system for mechanical vacuum-assisted aspiration embolectomy in the treatment of a wide variety of clinical situations involving acute peripheral arterial occlusions.

VDM: Can you briefly describe your
findings?

Dr Saxon: A total of 79 patients were enrolled: 39 (49.4%) underwent XTRACT as the initial therapy, and 40 (50.6%) underwent XTRACT after failed catheter-directed thrombolysis or other mechanical intervention, or for removal of distal emboli that occurred during an intervention. Complete or near-complete revascularization (Thrombolysis in Myocardial Infarction [TIMI] grade 2/3 flow) was achieved in 87.2% of patients (68 of 78) immediately after the XTRACT procedure and before any other intervention. Successful revascularization was achieved in 79.5% of patients (31 of 39) as an initial treatment and in 92.5% (37 of 40) as salvage or secondary therapy. Normal flow (TIMI grade 3) was achieved in 77.2% of patients (61 of 79) without any device-related complications. We concluded that XTRACT was safe and effective for revascularization of acute or subacute peripheral arterial occlusions as a primary therapy or as a secondary therapy after other endovascular techniques had failed.

VDM: Tell me about something surprising you encountered while doing this research.

Dr Saxon: It was surprising to me that XTRACT could work as well as it did after other techniques, such as CDT, had failed. It was not always effective, but it was relatively quick, simple to perform, and helpful.

VDM: How might your findings affect clinical practice?

Dr Saxon: I think the PRISM study confirms that aspiration thromboembolectomy has a role in a number of difficult clinical situations and adds another tool to the interventionalist’s “tool box” that should be considered when dealing with emboli or acute to subacute arterial thrombosis.

VDM: What future studies would you like to see take place? 

Dr Saxon: Using a modified TIMI score pre- and post-use of XTRACT and before any other interventions provided an objective assessment of how well the Penumbra/Indigo system worked. I would like to see this approach universally adopted in future studies assessing these types of technologies.

Although PRISM helped confirm the acute safety and technical success of XTRACT, long-term clinical outcomes in the setting of acute limb ischemia were not assessed. It would be helpful to have future studies assess the limb salvage efficacy of XTRACT as a component of an “endovascular-first” approach to the treatment of acute limb ischemia.

Finally, more research needs to be done on the use of larger devices (8 Fr and above) in the setting of substantial clot burden in larger arteries, such as the iliac and common femoral artery, in which XTRACT will likely be more difficult to perform. These situations were successfully treated in PRISM, but only in a small number of patients.

VDM: What are you hoping that attendees take away from your presentation?

Dr Saxon: I would like to have attendees leave with the understanding that aspiration embolectomy can be added to surgical embolectomy and catheter-directed thrombolysis as a helpful tool in the treatment of acute limb ischemia. It is safe and quick to perform in a variety of difficult clinical situations, such as the removal of organized atheroemboli that occur during an endovascular procedure, or as an alternative to catheter-directed thrombolysis in patients who cannot receive thrombolytic therapy. 

Abstract 

Purpose: The purpose of the trial was to examine the safety and clinical efficacy of XTRACT in a patient population with peripheral arterial occlusion. We report the outcome of the PRISM trial on the use of Penumbra/Indigo System as an initial and secondary approach for peripheral revascularization.

Materials and Methods: The PRISM trial is a single-arm, multicenter, and retrospective analysis of enrolled consecutive patients meeting the inclusion criteria of peripheral arterial occlusion (Thrombolysis in Myocardial Infarction [TIMI] 0–1) before treatment with the Penumbra/Indigo System. The primary endpoints were vessel patency immediately postprocedure as measured by TIMI scores, and the rate of serious adverse events (SAEs) within 24 hours of treatment with the study device.

Results: PRISM concluded with 79 patients enrolled. XTRACT was the primary treatment modality for 39 patients (49.4%); the remaining 40 patients (50.6%) were treated with XTRACT secondary to failure from CDT, other endovascular therapies, and distal emboli from preceding interventions. As the primary intervention, XTRACT was successful in 79.5% (31 of 39) of patients; as secondary therapy, 92.5% (37 of 40) of patients were successfully revascularized with XTRACT to TIMI 2–3. Overall, vessel patency (TIMI 2–3) was achieved in 87.2% (68/78) immediately after XTRACT and in 96.2% (76/79) of patients after additional adjunctive interventions. Procedural SAEs were reported in five patients (6.3%); none were device related. 

Conclusions: Thrombectomy using XTRACT was safe and effective as both primary and secondary intervention in patients with peripheral arterial occlusions.