From the Midwestern Vascular Surgical Society
Safety and efficacy of ultrasound-accelerated
catheter-directed lytic therapy in acute pulmonary
embolism with and without hemodynamic
instability
Madeline Nykamp,a Angela VandenHull,a Tyler Remund, PhD,a Angelo Santos, MD,b Patrick Kelly, MD,b
Greg Schultz, MD,b and Chad Laurich, MD,b Sioux Falls, SDak
Objective: The objective of this study was to evaluate the safety
and effectiveness of ultrasound-accelerated thrombolysis in
acute pulmonary embolism.
Methods: A retrospective study of 45 patients was performed to
evaluate treatment of acute pulmonary embolism at a single
center from January 2011 to December 2013. All patients
were diagnosed with computed tomography or ventilation-
perfusion scan and had hemodynamic instability (systolic
blood pressure <100 mm Hg) or right-sided heart strain evi-
denced by right ventricular dilation, septal deviation, or
hypokinesis by echocardiography or computed tomography.
EkoSonic catheters (EKOS Corporation, Bothell, Wash) were
placed into the affected pulmonary arteries, and recombinant
tissue plasminogen activator was infused through the catheters
at 0.5 to 1.0 mg/h per catheter.
Results: Hypotension (systolic blood pressure <100 mm Hg)
was present in 12 patients, with 100% resolution by treatment
Pulmonary embolism (PE) is a frequently observed
event, with most deaths resulting from right ventricular
pressure overload and right ventricular failure.1 Survivors
are at an increased risk of chronic pulmonary hypertension
and recurrent PE.2
Patients who present with systemic hypotension, cardio-
genic shock, or cardiac arrest are suffering a massive PE and
are considered at high risk. Patients with right ventricle
dysfunction without systemic hypotension are suffering a
submassive PE and are considered at intermediate risk. Right
ventricle dysfunction is defined as right ventricle dilation
(right ventricle to left ventricle [RV/LV] ratio $ 0.9) or
wall motion abnormalities (hypokinesis, septal wall devia-
tion). Finally, patients with low clot burden in the distal
From the Sanford Researcha; and the Sanford Vascular Associates.b
Author conflict of interest: none.
Presented at the Plenary Session of the Thirty-eighth Annual Meeting of the
Midwestern Vascular Surgical Society, Coralville, Iowa, September 4-6, 2014.
Reprint requests: Chad Laurich, MD, Sanford Vascular Associates, 1305 W
18th St, Sioux Falls, SD 57117-5039 (e-mail: chad.laurich@
sanfordhealth.org).
The editors and reviewers of this article have no relevant financial relation-
ships to disclose per the Journal policy that requires reviewers to decline
review of any manuscript for which they may have a conflict of interest.
2213-333X
Copyright Ó 2015 by the Society for Vascular Surgery. Published by
Elsevier Inc.
http://dx.doi.org/10.1016/j.jvsv.2015.03.001
completion. Tachycardia (heart rate >100 beats/minute) was
present in 26 patients and resolved in 92% by treatment
completion; the average heart rate for all patients decreased
from 109 to 77 beats/minute during the treatment period.
Direct pulmonary artery pressure measurement showed
average decrease of 21.5 mm Hg, representing a 40.2%
reduction. Postprocedure echocardiography demonstrated
complete resolution of cardiac dysfunction in 64%. Patients
received a total dose of 30.5 mg (range, 14-66 mg) recombi-
nant tissue plasminogen activator during an infusion time of
14.2 hours (range, 8-21 hours). There were no deaths
through 90 days of follow-up and no major periprocedural
bleeding events.
Conclusions: This retrospective study demonstrates the safety
and efficacy of current ultrasound-accelerated thrombolysis
methods to treat acute pulmonary embolism. (J Vasc Surg:
Venous and Lym Dis 2015;3:251-7.)
pulmonary vasculature and mild symptoms without signs
of right ventricular strain are suffering minor PE and are
considered to be at low risk.3,4
Typically, patients who are minimally symptomatic are
treated with systemic anticoagulation. Whereas these mini-
mally symptomatic patients tend to do well, patients pre-
senting with massive or submassive PE may require acute
intervention to relieve heart strain. In addition, catheter-
directed techniques for PE resolution may reduce the risk
of bleeding complications as the lytic agent can be concen-
trated near the target lesion and systemic dose can be
reduced. Current common methods of acute intervention
include intravenous fibrinolysis, catheter-directed throm-
bolysis, and transcatheter mechanical clot fragmentation
with or without thrombectomy. The goals of these thera-
pies are to debulk thrombus and to improve hemodynamic
stability. There has been some question surrounding
catheter-directed therapies in that infused medicine is
washed out into the nonoccluded portion of the artery,
minimizing its local effect.5 Other drawbacks to traditional
catheter-directed lytic therapies are relatively high cost,
extended treatment times, and potential renal injury from
repeated angiography.6-8
Interest has recently been generated in catheter-
directed treatment using ultrasound-accelerated thrombol-
ysis therapies for treatment of massive and submassive
PE.9-12 The high-frequency (2.2 MHz), low-power
251
 JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS
252 Nykamp et al July 2015

(3.5 W) ultrasonic waves are intended to improve delivery ventricular dilation, septal deviation, or hypokinesis by
of the thrombolytic agent to the clot by dissociation of the echocardiography or CT. Patients were determined to be
fibrin matrix, thus increasing the rate of clot dissolution hemodynamically unstable if they had tachycardia or
while reducing the risk of bleeding complications. It has hypotension. Tachycardia was defined as a heart rate of
been shown that high-frequency ultrasound induces struc- >100 beats/minute, and hypotension was defined as a
tural alteration in fibrin consistent with an increase in systolic blood pressure of <100 mm Hg. Patients were
permeability and increased accessibility of tissue plasmin- excluded if they had <1 month of life expectancy, if they
ogen activator to binding sites within fibrin fibers without were women of childbearing potential without adequate
causing damage to surrounding tissues.13 Although ultra- birth control measures taken, if they had uncontrolled
sound does hasten the process of fibrin degradation, it bleeding disorders, and if they were patients for whom
does not cause fragmentation and subsequent emboliza- thrombolytic drugs were contraindicated. Patients were
tion but instead creates plasma degradation of fibrin into monitored for bleeding complications, which were defined
soluble fragments.14 We have been performing thromboly- as hemorrhagic complication requiring interruption of
sis for high- and intermediate-risk cases of acute PE with thrombolysis, hemorrhagic complication requiring surgical
ultrasound-accelerated technology at our center for 3 years. intervention, and hemorrhagic complication requiring
The purpose of this review was to evaluate the safety and transfusion. On November 19, 2012, the Institutional
efficacy of ultrasound-assisted thrombolysis in acute PE. Review Board approved our access to the patients’ health
information for this retrospective study. Because the health
information of the patients was to be de-identified, the
METHODS Institutional Review Board did not require the patients to
Study design. This study is a single-center retrospec- be consented. Medical records were reviewed for relevant
tive review of 45 patients (26 men and 19 women) who clinical information, including lytic time, lytic dose,
were treated for acute massive or submassive PE from symptomatic improvement, hemodynamic parameters,
January 2011 to December 2013 (Table I). All patients bleeding complications, and survival.
were treated by use of the EkoSonic Endovascular System Intervention. In the vascular catheterization labora-
(EKOS, Bothell, Wash) with recombinant tissue plasmin- tory, the common femoral vein was accessed with ultrasound
ogen activator (rtPA) (Fig 1). Preprocedure diagnosis of guidance and a 6F sheath placed (Cordis Corporation,
PE was made by either computed tomography (CT) or Miami Lakes, Fla). For bilateral cases, both the right and
ventilation-perfusion scan. Decision for treatment was left common femoral veins were accessed. The patients had
based on clot burden by CT or evidence of right-sided varying extents of lesions (Table II). Carbon dioxide angi-
heart strain by hemodynamic parameters or pretreatment ography of the inferior vena cava (IVC) was performed, and
echocardiography. Patients were offered treatment if their a retrievable IVC filter (Eclipse [C. R. Bard, Inc, Tempe,
thrombus burden extended to the main or pulmonary ar- Ariz] or Option [Argon, Plano, Tex]) was positioned and
teries or right-sided heart strain was evidenced by right deployed from an infrarenal position in 37 of 45 cases. All
but nine of the originally placed filters have been retrieved
Table I. Patient demographics (Table III). The main pulmonary artery was selected using
an Omni Flush catheter (Angiodynamics, Latham, NY)
Treatment Control (Fig 2). Pulmonary artery pressure was measured directly
group group
through catheter transduction. Selective catheterization was
No. of patients 45 45 performed with placement of 6- or 12-cm EKOS lytic
Age, average 6 SD 58.5 6 17 69.2 6 13.2 catheters, depending on the bulk and location of thrombus
Hypertension 27 (63) 25 (55.6) burden; 50 mL of 0.9% saline was infused through each
Hypercholesterolemia 3 (7) 20 (44.4)
catheter as coolant. Heparin was infused at a set rate of 300
Tobacco use 8 (19) 12 (26.7)
Diabetes 11 (26) 12 (26.7) units/h per sheath (total, 600 units/h). Lytic therapy was
Coronary artery disease 7 (16) 9 (20) begun at 1.0 mg rtPA per hour per catheter and reduced to
Chronic obstructive 2 (5) 7 (15.6) 0.5 mg rtPA per hour per catheter after 4 hours until treat-
pulmonary disease ment completion. Fourteen patients received a bolus dose of
Renal insufficiency 6 (14) d
(creatinine $ 1.5 mg/dL) rtPA (average dose, 28.9 mg). This was part of a single
History of deep venous 6 (14) 9 (20) provider’s protocol, and all patients thus treated were given a
thrombosis bolus dose. All patients were monitored in an intensive care
History of PE 0 (0) 4 (8.9) unit setting during infusion. Treatment was complete with
Recent trauma 0 1 (2.2)
improvement in hemodynamic parameters and clinical
Recent major surgery 6 (13.3) 3 (6.67)
Current or recent cancer 7 (15.6) 9 (20) improvement. Lytic catheters and sheaths were discontinued
Identified hypercoagulable 6 (13.3) 2 (4.4) at the bedside. After the procedure, standard anti-
disorder coagulation was administered.
Idiopathic 26 (57.8) 30 (66.7) Treatment group. The 45 patients treated with the
PE, Pulmonary embolism; SD, standard deviation. interventional protocol had an average age of 58.5 years;
Data are presented as number (%) unless otherwise indicated. 6 of the patients had a recent surgery, 7 of the patients
JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS
Volume 3, Number 3 Nykamp et al 253

Fig 1. The EkoSonic device used in this study. A, The instrumentation and control unit with accompanying catheters.
B, Close-up view of the catheter tips. (Reproduced with permission of the EKOS Corporation, Bothell, Wash.)

had current or recent cancer, 6 of the patients had a hyper- had bilateral disease. Forty of the patients presented with
coagulable condition, and 26 of the patients had PE of an right-sided heart strain, 4 had hypotension, and 11 had
idiopathic nature (Table I). Forty-four of the patients had tachycardia (Table II).
bilateral disease. Thirty-seven patients presented with right-
sided heart strain, 13 had hypotension, and 26 had
RESULTS
tachycardia (Table II). All patients treated with EKOS
demonstrated hemodynamic instability or right-sided heart Treatment group. Technical success, defined as suc-
strain by echocardiography, right ventricle dilation by CT cessful placement of catheters and initiation of lytic therapy,
scan, or pulmonary hypertension by direct catheter was achieved in 100% of patients. Of those 45 patients, 44 un-
measurement. derwent bilateral treatment. For all patients, a total dose of
Control group. Forty-five intermediate-to high-risk 30.5 mg (range, 14-66 mg) rtPA was given during 14.2 hours
PE patients who were treated with systemic infusion of (range, 8-21 hours) (Table III). Subset analysis revealed that
heparin or anticoagulation from 2011 to 2013 were 31 patients did not receive a bolus and received a total dose of
randomly selected, and their charts were reviewed for 22.5 mg rtPA (range, 14-48 mg). Fourteen patients received
similar demographics (Table I), baseline characteristics a bolus dose of 28.9 mg rtPA (range, 25-40 mg) and a total
(Table II), periprocedural parameters, and follow-up in- dose of 48.3 mg rtPA (range, 37-66 mg). The 12 patients
formation as the treatment group. All patients were treated presenting with hypotension had 100% resolution by treat-
according to institutional protocol for systemic heparin ment completion. Of the patients who presented with hy-
infusion for PE. The average age of the control group potension, their systemic systolic pressure increased from
patients was 69.2 years; 1 of the patients had history of 81.8 to 125.2 mm Hg. Of the 26 patients who presented
recent trauma, 3 had recent major surgery, 9 had current or with tachycardia, 92% of the cases resolved by treatment
recent cancer, 2 had a hypercoagulable condition, and 30 completion. The average heart rate of patients with tachy-
had idiopathic PE (Table I). Thirty-eight of the patients cardia decreased from 119.9 to 84.0 beats/minute during
the treatment period (Table III). Direct pulmonary artery
Table II. Patient baseline characteristics pressure measurements showed an average decrease of
21.5 mm Hg, representing a 40.2% decrease. The post-
Treatment Control
group, group,
procedure echocardiogram demonstrated normal cardiac
No. (%) No. (%) function in 64% of the patients. Patients who were not un-
dergoing inpatient treatment for another condition or an
Location of PE unrelated surgery remained in the hospital for an average of
Bilateral 44 (97.8) 38 (84.4) 3.3 days, which was shorter by a statistically significant margin
Saddle 9 (20) 3 (6.67)
Bilateral main pulmonary artery 11 (24.4) 9 (20) than the control group treated with heparin alone. All pa-
Single main pulmonary artery 1 (2.2) 7 (15.6) tients survived to discharge. Through 90 days of follow-up,
Hemodynamic parameters there were no deaths and no reported episodes of recurrent
Right-sided heart strain 37 (86) 40 (88.9) PE. There were no major periprocedural bleeding events.
Dyspnea 43 (100) d
One significant gastrointestinal bleed was noted in an alco-
Hypotension 13 (30) 4 (8.9)
Chest pain 22 (51) 23 (51.1) holic patient with a supratherapeutic international normal-
Concomitant deep venous 8 (19) 1 (2.2) ized ratio 30 days after treatment. Average follow-up was
thrombosis 22.5 months. Survival in the treatment group was a statisti-
Tachycardia 26 (60) 11 (24.4) cally significant improvement when compared to the control
Syncope 11 (26) 3 (6.7)
group (Fig 3). Six of the 45 patients had residual pulmonary
PE, Pulmonary embolism. hypertension at follow-up per echocardiography (Table IV).
 JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS
254 Nykamp et al
Table III. Perioperative and postoperative data
Thrombolytic dose, mg
Thrombolytic time, average hours 6 SD
IV heparin time, hours
In-hospital bleeding complication
IVC filter placement
IVC filter removal
Preprocedural systolic blood pressure of hypotensive patients, mm Hg
Postprocedural systolic blood pressure of hypotensive patients, mm Hg
Preprocedural heart rate of patients with tachycardia, beats/minute
Postprocedural heart rate of patients with tachycardia, beats/minute
Preprocedural pulmonary artery pressure, mm Hg
Postoperative pulmonary artery pressure, mm Hg
Length of hospital stay, average days 6 SDa
IV, Intravenous; IVC, inferior vena cava; SD, standard deviation.
a
Statistically significant according to Student t-test.
Control group. Of the patients treated with a systemic
infusion of heparin, the average infusion time was
99.5 hours. There was only one bleeding complication,
which was a gastrointestinal bleed that required stopping
of the intravenous infusion. Fourteen patients had an
IVC filter placed before the procedure, and 3 of the
14 IVC filters were removed to date. Of the patients
who originally presented with hypotension, the average sys-
tolic blood pressure rose from 95 to 111.8 mm Hg. Of the
patients who presented with tachycardia, the average heart
rate decreased from 110.4 to 76.9 beats/minute. The
Fig 2. Perioperative fluoroscopic image (arrows show the EKOS
catheters in the pulmonary arteries bilaterally).
July 2015
Treatment group Control group
30.5 (range, 14-66) d
14.2 6 4.0 d
14.2 6 4.0 99.5 6 64.9
0/45 1/45
37/45 14/45
28/37 3/14
81.8 (range, 51-101) 95 (range, 86-100)
125.2 (range, 106-163) 111.75 (range, 96-136)
119.9 (range, 102-168) 110.4 (range, 101-126)
84.0 (range, 66-110) 76.9 (range, 59-100)
53.5 (range, 38-110) d
32.0 (range, 24-45) d
3.2 6 2.0 6.7 6 4.4
length of stay for patients treated with systemic heparin
infusion was 6.7 6 4.4 days. Average follow-up was
18.9 months (Fig 3). Three of the eight patients tested had
residual pulmonary hypertension at follow-up per echo-
cardiography. None of the patients treated with systemic
infusion had recurrent PE (Table IV).
DISCUSSION
Safe and successful treatment of patients with massive
and submassive PE was demonstrated in this retrospective
study. Results revealed resolution of hypotension and
tachycardia and a 40.2% decrease in pulmonary artery pres-
sure. Survival was excellent, with no deaths through
90 days. No major periprocedural bleeding complications
were observed. These results were achieved with an average
dose of 30.5 mg rtPA, much lower than the current Food
and Drug Administration-approved 100 mg rtPA systemic
treatment dose and lower than in other reports.3,10,15,16
Other published reports have demonstrated that 44%
of PE patients who present with right-sided heart dysfunc-
tion suffered from pulmonary hypertension at 1 year,
defined as pulmonary artery pressure >30 mm Hg or
moderately or severely reduced right ventricular function.
These patients had baseline peak pulmonary artery pressure
>50 mm Hg.17 In our treatment group, 14 of the 37
patients who originally presented with right-sided heart
strain had their pulmonary pressures measured in follow-
up. Of the 14 patients, 5 (35.7%) had residual pulmonary
hypertension. A relationship between decreased pulmonary
artery pressures and improvement of right ventricular
dysfunction was likewise demonstrated.18
Right-sided heart dysfunction is also associated with
both mortality and recurrent PE. Right ventricular hypoki-
nesis was associated with a 57% higher 3-month mortality
rate in a review of 2452 PE patients; 88.9% of these pa-
tients were hemodynamically stable but went on to a 22%
mortality rate at 3 months.3 Right-sided heart strain,
defined as RV/LV ratio >0.9, was also determined to be
an independent predictor for hospital mortality and unre-
solved right ventricular dysfunction, which led to an
JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS
Volume 3, Number 3 Nykamp et al 255

Fig 3. The 24-month survival for patients who have met specific follow-ups. The improvement in survival of the
treatment group to 2 years is statistically significant according to the log-rank c2 test.

eightfold increase in recurrent PE risk and a fourfold in- to maintain their clinical benefit. These patients had similar
crease in mortality risk.19,20 baseline characteristics to patients who received a bolus
In long-term follow-up, PE patients treated with intra- dose. This observation provides further support for the
venous thrombolytics had lower pulmonary artery pres- efficacy of treatment with ultrasound-assisted lytic cathe-
sures and pulmonary vascular resistance than PE patients ters. In our set of patients, 37 of 45 patients received an
treated with heparin alone.21 The current study demon- IVC filter, and 26 of those 37 originally placed IVC filters
strates that treatment with ultrasound-assisted thromboly- have since been retrieved. Patients in the treatment group
sis with low-dose rtPA reduced pulmonary artery were not fully anticoagulated. Instead, they received only
pressures by 40.2% during an average treatment time of 300 mL of heparin per sheath per hour while the sheaths
14.2 hours. Improvement in right ventricular dysfunction were placed. Because they were not fully anticoagulated,
was evidenced by correction of hemodynamic parameters we thought it important that an IVC filter be placed in
with resolution of hypotension and improvement in tachy- patients we believed were at risk of an embolic complica-
cardia. Success was further confirmed by no mortalities in tion. The only load of contrast material that our patients
the hospital or at 90 days. This compares favorably with a received was from their chest CT scans. Given this load
previously reported rate of 22%.3 of contrast material, we thought it important to avoid addi-
Other reports have demonstrated a low incidence of tional administration of contrast material during the inter-
procedure-related complications, attesting to the safety of vention. We used carbon dioxide angiography when
the device and protocol. Our study demonstrated no major placing the IVC filter. In our experience, there is no
periprocedural bleeding complications but maintained clin- need for injection of a contrast agent in crossing the lesions
ical benefit at even lower doses of rtPA (average dose of in the pulmonary arteries. We use an Omni Flush catheter
30.5 mg vs range of 35 to 45 mg for other protocols). and a stiff angled Glidewire (Terumo, Somerset, NJ) to
This can be contrasted with our control group treated achieve the pulmonary artery. Once we advance the
with intravenous heparin, which had one bleeding compli- Omni Flush into the right atrium, we pull the precurved
cation (gastrointestinal) that required stopping of the treat- portion down against the wall of the right atrium gently,
ment. Subset analysis revealed that patients receiving no and this pressure temporarily straightens the precurved
bolus dose averaged 22.5 mg of rtPA, but they continued portion of the Omni Flush catheter, directing the distal
tip toward the pulmonary arteries. From here, we advance
Table IV. Follow-up information an angled Glidewire toward the pulmonary arteries and
select them as needed. We verify the location of our wires
Treatment group Control group and device with fluoroscopy.
It is important to check patients for a hypercoagulable
3 months 45 45 condition during follow-up to avoid recurrent PE. We
6 months 45 45 check patients at their 3- or 6-month follow-up for a num-
12 months 42 38
18 months 20 32 ber of factors, including factor V Leyden, antithrombin III,
24 months 13 24 protein C and S deficiency, antiphospholipid antibody syn-
Residual pulmonary 6/45 3/8 drome, and prothrombin gene mutation. In Table I, we
hypertension report six patients in the treatment group and two patients
Recurrent PE 0/45 0/45
in the control group who tested positive for a hypercoagu-
PE, Pulmonary embolism. lable condition.
 JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS
256 Nykamp et al
The lesions were crossed with a Glidewire and catheters
inserted over the Glidewire, but there was no direct me-
chanical fragmentation in the sense that has been described
in other reports. The reason is the ability of ultrasound to
change the conformation of the fibrin, exposing the bind-
ing sites necessary for the tPA to act while simultaneously
disassociating the fibrin matrix. One report of 18 patients
treated with pigtail thrombectomy followed by aspiration
in 13 patients reported an increase in systemic systolic pres-
sure from 74.3 6 7.5 to 89.4 6 11.3 mm Hg. They also
observed a decrease in mean pulmonary artery pressure
from 37.1 6 8.5 to 32.3 6 10.5 mm Hg. They reported
an in-hospital major complication rate of 11.1% but did
not report pulmonary hypertension rates during the
follow-up.22 A more recent study described 50 patients
who were treated with pigtail thrombectomy followed by
intrapulmonary thrombolysis. The investigators reported
a reduction in mean pulmonary artery pressure from
41 6 8 mm Hg to 24.52 6 6.89 mm Hg. They also had
four patients who suffered minor in-hospital complica-
tions.23 This protocol called for 24 hours of systemic hep-
arin after the mechanical thrombectomy. Alternatively, our
localized lytic therapy lasted only 14.2 hours on average
and was not followed by heparin. Compared with reports
of mechanical thrombectomy, efficacy appears to be
improved or similar, whereas incidence of complications
appeared to be less.
The current study has several limitations. It is retro-
spective in design and lacks a control group. Complete
data sets for pulmonary artery pressures were not docu-
mented in all patients, and follow-up echocardiograms like-
wise were not documented uniformly. Pretreatment CT
evaluation for RV/LV ratio was not performed, nor were
routine follow-up CT scans. Full pulmonary angiograms
were not obtained; CT and pretreatment echocardiography
findings were relied on along with pulmonary artery pres-
sures. Whereas pulmonary angiograms would have pro-
vided another objective measurement, it was thought that
the other measures were adequate with the benefit of
reduced use of contrast material, often in patients who
had just received a chest CT. The treatment lasted several
hours, and the patient was transferred to the intensive
care unit for most of the treatment. We thought the
increased cost of taking the patient back to the catheteriza-
tion laboratory and the risk of an additional load of contrast
material were not justified. Whereas the results with the
ultrasound-assisted lytic catheter demonstrated excellent
efficacy, direct comparison with other traditional methods
of therapy cannot be assessed.
CONCLUSIONS
Treatment with rtPA through an ultrasound-assisted
lytic catheter has been shown to be an effective treatment
for reducing pulmonary artery pressures and resolving
hemodynamic abnormalities, with excellent mortality and
complication rates. Despite these positive findings, pro-
spective studies are required to compare ultrasound-
assisted lytic therapy to traditional therapies.
July 2015
AUTHOR CONTRIBUTIONS
Conception and design: CL
Analysis and interpretation: CL, GS, AS, PK
Data collection: GS, AS, PK, AV, TR, MN
Writing the article: CL, TR
Critical revision of the article: CL
Final approval of the article: CL
Statistical analysis: TR
Obtained funding: Not applicable
Overall responsibility: CL
REFERENCES
1. Piazza G, Goldhaber SZ. The acutely decompensated right ventricle:
pathways for diagnosis and management. Chest 2005;128:1836-52.
2. Piazza G, Goldhaber SZ. Acute pulmonary embolism: part II: treat-
ment and prophylaxis. Circulation 2006;114:e42-7.
3. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism:
clinical outcomes in the International Cooperative Pulmonary Embo-
lism Registry (ICOPER). Lancet 1999;353:1386-9.
4. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N,
Goldhaber SZ, et al. Management of massive and submassive pulmo-
nary embolism, iliofemoral deep vein thrombosis, and chronic throm-
boembolic pulmonary hypertension: a scientific statement from the
American Heart Association. Circulation 2011;123:1788-830.
5. Schmitz-Rode T, Kilbinger M, Gunther RW. Simulated flow pattern in
massive pulmonary embolism: significance for selective intrapulmonary
thrombolysis. Cardiovasc Intervent Radiol 1998;21:199-204.
6. Sharafuddin MJ, Hicks ME. Current status of percutaneous mechanical
thrombectomy. Part I. General principles. J Vasc Interv Radiol 1997;8:
911-21.
7. Sharafuddin MJ, Hicks ME. Current status of percutaneous mechanical
thrombectomy. Part II. Devices and mechanisms of action. J Vasc
Interv Radiol 1998;9(1 Pt 1):15-31.
8. Sharafuddin MJ, Hicks ME. Current status of percutaneous mechanical
thrombectomy. Part III. Present and future applications. J Vasc Interv
Radiol 1998;9:209-24.
9. Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J,
Heitzer T, et al. Randomized, controlled trial of ultrasound-assisted
catheter-directed thrombolysis for acute intermediate-risk pulmonary
embolism. Circulation 2014;129:479-86.
10. Kennedy RJ, Kenney HH, Dunfee BL. Thrombus resolution and he-
modynamic recovery using ultrasound-accelerated thrombolysis in
acute pulmonary embolism. J Vasc Interv Radiol 2013;24:841-8.
11. Dumantepe M, Uyar I, Teymen B, Ugur O, Enc Y. Improvements in
pulmonary artery pressure and right ventricular function after
ultrasound-accelerated catheter-directed thrombolysis for the treat-
ment of pulmonary embolism. J Card Surg 2014;29:455-63.
12. Stambo GW, Montague B. Bilateral EKOS EndoWave catheter
thrombolysis of acute bilateral pulmonary embolism in a hemody-
namically unstable patient. South Med J 2010;103:455-7.
13. Braaten JV, Goss RA, Francis CW. Ultrasound reversibly disaggregates
fibrin fibers. Thromb Haemost 1997;78:1063-8.
14. Blinc A, Francis CW, Trudnowski JL, Carstensen EL. Characterization
of ultrasound-potentiated fibrinolysis in vitro. Blood 1993;81:2636-43.
15. Fiumara K, Kucher N, Fanikos J, Goldhaber SZ. Predictors of major
hemorrhage following fibrinolysis for acute pulmonary embolism. Am J
Cardiol 2006;97:127-9.
16. Kanter DS, Mikkola KM, Patel SR, Parker JA, Goldhaber SZ.
Thrombolytic therapy for pulmonary embolism. Frequency of intra-
cranial hemorrhage and associated risk factors. Chest 1997;111:
1241-5.
17. Ribeiro A, Lindmarker P, Johnsson H, Juhlin-Dannfelt A,
Jorfeldt L. Pulmonary embolism: one-year follow-up with echocar-
diography doppler and five-year survival analysis. Circulation 1999;
99:1325-30.
18. Lin PH, Annambhotla S, Bechara CF, Athamneh H, Weakley SM,
Kobayashi K, et al. Comparison of percutaneous ultrasound-accelerated
JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS
Volume 3, Number 3
thrombolysis versus catheter-directed thrombolysis in patients with
acute massive pulmonary embolism. Vascular 2009;17(Suppl 3):
S137-47.
19. Fremont B, Pacouret G, Jacobi D, Puglisi R, Charbonnier B,
de Labriolle A. Prognostic value of echocardiographic right/left ven-
tricular end-diastolic diameter ratio in patients with acute pulmonary
embolism: results from a monocenter registry of 1,416 patients. Chest
2008;133:358-62.
20. Grifoni S, Vanni S, Magazzini S, Olivotto I, Conti A, Zanobetti M,
et al. Association of persistent right ventricular dysfunction at hospital
discharge after acute pulmonary embolism with recurrent thrombo-
embolic events. Arch Intern Med 2006;166:2151-6.
Nykamp et al 257
21. Sharma GV, Folland ED, McIntyre KM, Sasahara AA. Long-term
benefit of thrombolytic therapy in patients with pulmonary embolism.
Vasc Med 2000;5:91-5.
22. Eid-Lidt G, Gaspar J, Sandoval J, de los Santos FD, Pulido T, Gonzalez
Pacheco H, et al. Combined clot fragmentation and aspiration in
patients with acute pulmonary embolism. Chest 2008;134:54-60.
23. Mohan B, Aslam N, Kumar Mehra A, Takkar Chhabra S, Wander P,
Tandon R, et al. Impact of catheter fragmentation followed by local
intrapulmonary thrombolysis in acute high risk pulmonary embolism as
primary therapy. Indian Heart J 2014;66:294-301.
Submitted Oct 21, 2014; accepted Mar 1, 2015.