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Abstract

We summarize the evidence for the safety and efficacy of catheter-directed thrombolysis (CDT) with and without ultrasound-assisted therapy for treating submassive and massive pulmonary embolism (PE) in a systematic review. The primary efficacy outcome was mortality. Outcomes were pooled across studies with the random-effects model. Twenty-four studies enrolled 700 patients in total; 653 received mechanical thromboembolectomy treatments for PE (mortality rate, 9% [95% confidence interval (CI), 6%-13%], P = .12; rate of minor complications, 6% [95% CI, 2%-13%]). In the ultrasound-accelerated thrombolysis (USAT) studies, the mortality rate was 4% (95% CI, 1%-11%) and in the non-USAT studies, it was 9% (95% CI, 6%-13%). Secondary safety outcomes were all bleeding events, which occurred in 12% (95% CI, 7%-20%) of the USAT studies and in 10% (95% CI, 5%-20%) of the non-USAT studies. Current clinical evidence does not prove USAT is superior over CDT methods.

Keywords

catheter-directed thrombolysis pulmonary embolism thrombolysis

Introduction

Venous thromboembolism, including pulmonary embolism (PE) and deep vein thrombosis, is a major contributor to the global disease burden and a leading cause of disability and lost income.^1,2 Although the 30-day survival for venous thromboembolism is 75%, sudden death is the clinical presentation of PE for almost a quarter of patients.^3,4 The primary treatment of PE is anticoagulation; however, thrombolysis may be used in high-risk patients.^5
–7 For these patients, current guidelines favor systemic use of thrombolytics over catheter-directed approaches.^5,6 In a recent meta-analysis⁸ with over 2000 patients enrolled in randomized controlled trials, systemic thrombolysis was evaluated among patients with severe PE; the use of thrombolytics was associated with lower all-cause mortality compared to the use of anticoagulants alone, but this was in exchange for a higher risk of major bleeding (9.2%) and a 1.5% incidence of intracranial hemorrhage. Despite measurable reduction in PE-associated mortality, it is estimated that only 30% of hemodynamically unstable patients receive thrombolysis.⁹

Catheter-directed thrombolysis (CDT) offers an alternative for patients who have a high risk of bleeding and contraindications for systemic thrombolysis. CDT may be administered conventionally through a catheter with multiple sideholes and direct thrombolytic infusion into the pulmonary arteries.¹⁰ Delivery methods have evolved, however, plausibly improving the safety profile of the procedure. In addition, ultrasound-accelerated thrombolysis (USAT) is a novel pharmacomechanical thrombolysis method that combines CDT and ultrasound energy to improve the delivery of thrombolytic agents.¹⁰ We sought to summarize the evidence for the safety and efficacy of conventional CDT versus USAT for the treatment of submassive and massive PE.

Methods

With the assistance of an expert research librarian, we performed a systematic review by searching several electronic databases, including Medline, Embase, Scopus, and Cochrane, for studies published from October 2009 through October 2014. We elected to exclude studies older than 2009 to focus on the more current outcomes and technology. The search terms were mechanical thrombectomy, mechanical thromboembolectomy, mechanical thrombolytic therapy, mechanical thrombolysis, and pulmonary embolism. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement for reporting this systematic review.¹¹ The process of study selection is outlined in the Figure 1.

Figure 1.

PRISMA flow diagram. (Adapted from Moher et al¹¹ and used with permission.).

There was no language restriction; we limited abstraction to case series with more than 5 patients. Unpublished abstracts were included in the search. All data were abstracted by at least 2 independent reviewers; if a discrepancy occurred, a third reviewer adjudicated the disagreement. Studies were included in the analysis if they enrolled patients with acute PE and provided outcome data on complications and mortality. Mortality was the main efficacy outcome. Complications were categorized as minor if no therapy or nominal therapy was required or as major if the complication required longer hospitalization or caused permanent adverse sequelae or death.¹² Bleeding complications were analyzed separately as a safety outcome and were defined as major bleeding if patients required a transfusion of blood products, if their hemoglobin level decreased by a least 2 g/dL, or if bleeding occurred in critical organs. We also extracted the method of diagnosis, severity of PE, clot burden as reported by the Miller index,¹³ use of thrombolytic agents, pulmonary pressures, and hospital length of stay in days.

We evaluated the methodologic quality (risk of bias) of the included studies according to selected items relevant to uncontrolled studies, focusing on cohort selection, loss of follow-up, and ascertainment of the outcomes and exposure.

Statistical Analysis

The included studies were uncontrolled (ie, without a comparison group), so we could only estimate incidence rates (ie, the event rate at the end of study follow-up). Rates were pooled across studies with the random-effects model.¹⁴ Heterogeneity was assessed with the I ² statistic, with a value over 50% implying substantial heterogeneity.¹⁵ We also conducted the Cochran Q test for heterogeneity, with a P value less than .05 being consistent with statistically significant heterogeneity. Data were insufficient to evaluate the presence and impact of publication bias.

Results

The electronic search identified 1104 references (Figure 1). A manual search identified 51 additional references. The meta-analysis included 24 studies with a total of 700 patients, of which 653 received endovascular treatments for PE. Although 2 studies by Engelhardt et al were selected for full review, only 1 study¹⁶ was included because the second one contained duplicated information. The study by Lin et al¹⁷ allowed for abstraction of USAT separately from conventional CDT; thus, the data were analyzed separately along with 5 more studies that were USAT-specific (Table 1). We included a total of 7 abstracts. Most of the studies were retrospective, and only 1 study was a randomized controlled trial. All studies allowed inclusion of both massive and submassive PE. The risk of bias was high because most of the studies included nonconsecutive patients and were uncontrolled (Table 2). The mean age of participants was 58 years (Table 1). Follow-up time ranged from 1 month to 5 years.

Table 1.

Demographics of Patients in 24 Studies of Catheter-Directed Thrombolysis.

Author, Year of Publication	Country	Patients, No.	Female, %	Patient Age, Mean (SD), y
Randomized controlled trial
Kucher et al, 2014²	Germany and Switzerland	59	53	63 (14)
Registries
Kuo et al, 2015¹²	United States and Spain	101	47.5	60
Ruzsa et al, 2014¹⁸	Hungary	26	NR	52.5 (14.9)
Cohort studies
Arzamendi et al, 2010¹⁹	Canada	10	70	43.7 (18.8)
Gao et al, 2011²⁰	China	46	58	52.3 (13.4)
Retrospective studies
Chamsuddin et al, 2008²¹	United States	10	50	54.2
Chechi et al, 2009²²	Italy	60	51	66.7 (13.8)
Lin et al, 2009¹⁷	United States	25	52	NR
Lin et al, 2009 EKOS^a17	United States	11	55	59 (17)
Zhou et al, 2009²³	China	28	28.5	63.7 (11.1)
Mohan et al, 2010²⁴	India	7	14	46.8 (12.2)
Ferrigno et al, 2011²⁵	United States	16	56	54.4 (15.8)
Hubbard et al, 2011²⁶	United States	12	18.8	60.2
Cuculi et al, 2012²⁷	Switzerland	63	41	60 (15)
Engelhardt et al, 2012¹⁶	United States	42	NR	58 (16)
Liu et al, 2012²⁸	China	20	40	NR
Munakata et al, 2012²⁹	Japan	10	80	58.1
Nassiri et al, 2012³⁰	United States	15	47	59 (16)
Kennedy et al, 2013³¹	United States	60	42	61 (16)
Akin et al, 2014³²	United States	17	52.9	60.1
Al-Hakim et al, 2014³³	United States	18	50	54.8
Fernandez et al, 2014³⁴	Argentina	14	35.7	64.5 (14.3)
Ivanauskiene et al, 2014³⁵	Lithuania	20	35	58.4 (15.3)
Quintana et al, 2014³⁶	United States	10	40	NR

Abbreviation: NR, not reported.

^aEkoSonic, Endovascular System; EKOS Corp.

Table 2.

Published Studies That Met Inclusion Criteria.

Author, Year of Publication	PE Definition and Assessment^a	Treatment^a
Randomized controlled trial
Kucher et al, 2014²	CT-confirmed PE Embolus in ≥1 main or proximal lower lobe pulmonary artery RV/LV ≥1 on echocardiographic apical 4-chamber view Troponin test positive Qanadli index for pulmonary occlusion score Pre Sys PAP, 52 (11.5) mm Hg Pre PAP, 30.2 (9.1) mm Hg	All patients treated with EkoSonic MACH4e Endovascular Systems^b and continuous infusion of rtPA Mean total rtPA dose 20.8 ± 3.0 mg for bilateral USAT (1 device per lung) and 10.5 ± 0.6 mg for unilateral (1 lung treated) USAT. Post Sys PAP, 39.7 (10.3) mm Hg Post PAP, 24.1 (6.7) mm Hg
Registries
Kuo et al, 2015¹²	Massive PE and submassive PE Pre PAP, 51.17 (14.06) mm Hg	Patients underwent (1) catheter-directed thrombectomy (mechanical or pharmacomechanical) or (2) CDT (low-dose hourly tPA or urokinase) or (3) both Mean thrombolytic doses were 28.0 ± 11 mg for rtPA and 2 697 101 ± 936 287 International Units for urokinase. On follow-up echocardiography, 87.5% showed improvement in right-sided heart strain Post PAP, 37.23 (15.81) mm Hg
Ruzsa et al, 2014¹⁸	Analysis of patients’ clinical, interventional, and echocardiographic data Pre Sys PAP, 60.78 (18.7) mm Hg	CDT was started with alteplase over a pigtail catheter Mean alteplase dose note reported. Control pulmonary angiography was performed When CDT was not successful, manual thrombectomy and thrombus fragmentation were performed Post Sys PAP, 19.7 (12.36) mm Hg
Cohort studies
Arzamendi et al, 2010¹⁹	Diagnosis of PE was based on clinical presentation and confirmed by $\dot{V} / \dot{Q}$ scintigraphy or angiographic CT Cardiac transthoracic echocardiography was systematically performed to confirm RV dysfunction Pulmonary angiograms were analyzed with the Miller index Pre PAP, 35.61 mm Hg Pre Miller index, 22.4 mm Hg	Thrombectomy with an AngioJet^c catheter Mean ___________ Local perfusion of fibrinolytic therapy with tenecteplase Post PAP, 26.91 mm Hg Post Miller index, 9.8 mm Hg
Gao et al, 2011²⁰	Diagnosis was confirmed by pulmonary angiography RV dysfunction from echocardiographic findings Pre PAP, 57.2 (6.2) mm Hg	Pigtail catheter After fragmentation and manual aspiration of thrombus, urokinase (500 000–750 000 units) was injected into the central pulmonary artery Post PAP, 36.3 (4.1) mm Hg
Retrospective studies
Chamsuddin et al, 2008²¹	PE diagnosed with CT of the chest with contrast material and $\dot{V} / \dot{Q}$ imaging	US-assisted CDT with the EndoWave Infusion Catheter System^b Thrombolytics used: urokinase, tPA, and reteplase Mean tPA dose was 0.88 mg/h ± 0.19 (median, 1.00 mg/h). One patient treated with urokinase was started on a dose of 60 000 U/h, and this was changed at 12 hours to 90 000 U/h. Another patient was treated with Reteplase (0.5 mg/h then 0.25 mg/h). Mean time of thrombolysis was 24.76 hours ± 8.44.
Chechi et al, 2009²²	PE diagnosed with CT, $\dot{V} / \dot{Q}$ scintigraphy, or echocardiography Angiographic massive PE was defined as Miller index ≥17	AngioJet^c rheolytic thrombectomy Locoregional fibrinolytic therapy with rtPA at a dose of 0.6 mg/kg over 15 minutes.
Lin et al, 2009¹⁷	Diagnosis of massive PE was based on CT, angiography, $\dot{V} / \dot{Q}$ scintigraphy, echocardiography, and physical examination Angiographic analysis based on the Miller index	Massive PE was treated with either USAT: EkoSonic Endovascular System^b or CDT intervention Thrombolytic agents for CDT infusion: urokinase and tPA. CDT: mean tPA dose rate was 0.93 ± 0.22 mg/h, for a mean total tPA dose of 25.43 ± 5.27 mg (range 16-45 mg). Mean urokinase starting dose was 60 000 U/h, which was increased at 6 hours to a mean dose of 90 000 U/h. The mean total urokinase dose was 2.04 ± 0.56 million units (range 1.65-2.87 million units)
Lin (EkoSonic^b) et al, 2009¹⁷	Pre Miller index PAP, 18.65 (3.25) mm Hg	In the EkoSonic Endovascular System^b group, tPA was used Mean tPA dose rate of 0.86 ± 0.16 mg/h for a mean total tPA dose of 17.2 ± 2.36 mg. Post Miller index, 5.84 (1.57) mm Hg
Zhou et al, 2009²³	Acute massive PE was diagnosed with contrast-enhanced CT and confirmed with angiography After measurement of PAP, selective pulmonary angiography identified the thrombus Pre PAP, 34.2 (4.8) mm Hg	Pigtail catheter was inserted to the thrombus site Urokinase at a dose of 100 000 U was administered through the. Thrombolysis could be repeated according to the patients’ situation with total dose of urokinase no more than 300 000 U Post PAP, 25.2 (5.1) mm Hg
Mohan et al, 2010²⁴	Catheter-directed intervention after angiographically confirmed massive PE Miller index >0.6 Pre Sys PAP, 73 (2.38) mm Hg Pre PAP, 44.99 (4.1) mm Hg Pre Miller index, 19.3 (4.1) mm Hg	Mechanical breakdown with 5F multipurpose and pigtail catheters Followed by intralesional infusion of urokinase Initial bolus dose of Urokinase (4400 IU/kg body weight) was given over 10 minutes followed by continuous infusion of 4400 IU/kg/h for 24 hours. Post Sys PAP, 39.7 (10.43) mm Hg Post PAP, 26.57 (7.99) mm Hg Post Miller index, 6.0 (1.7) mm Hg
Ferrigno et al, 2011²⁵	ACCP criteria were used to define whether the PE was massive or submassive and whether RV dysfunction was severe or mild PESI was calculated Miller index was calculated retrospectively Serum cardiac troponin I was measured before intervention Mean PAPs were obtained before the procedure and at the end of the procedure Pre PAP, 38.46 mm Hg Pre Miller index, 18.3125 mm Hg	Pulmonary embolectomy with the AngioJet^c device in combination with rtPA infused in the power-pulse-spray mode. The amount of r-tPA administered ranged from 10 to 20 mg. Transthoracic echocardiogram was repeated 24-48 hours after intervention Post PAP, 30.13 mm Hg Post Miller index, 9.0625 mm Hg
Hubbard et al, 2011²⁶	Diagnosis of PE with contrast-enhanced CTPA Echocardiography Massive PE: CTPA criteria, Miller index >17, right-sided heart strain (CTPA or echocardiography) Pulmonary angiography with standard angiographic techniques Pre PAP, 38.6 mm Hg Pre Miller index, 23 mm Hg	Rheolytic mechanical thrombectomy (AngioJet^c) with or without adjunctive catheter-directed tPA infusion Mean intraprocedural, infusion, and total doses of tPA were 7, 19.7, and 26.7 mg, respectively. Post PAP, 28.7 mm Hg Post Miller index, 13.5 mm Hg
Cuculi et al, 2012²⁷	Diagnosis of PE with CT, RV dilatation, or elevation of cardiac necrosis markers (preferably troponin) Pre Sys PAP, 53 (15) mm Hg Pre PAP, 33 (8) mm Hg	Multipurpose or pigtail catheter Local thrombolysis initiated with bolus injection of urokinase of 125 000 U in each microcatheter. The catheters were left in place for ≥24 hours with continuous infusion of urokinase (250 000 U/6 h/catheter), Post Sys PAP, 36 (12) mm Hg Post PAP, 21 (7) mm Hg
Engelhardt et al, 2012¹⁶	Chest CT scans for confirmation of PE RV dysfunction was characterized by the RV: LV dimension Thrombus burden was assessed with the modified Miller index Pre Miller index, 18 (5.1) mm Hg	USAT^b with rtPA Mean rt-PA dose was 33.5 ± 15.5 mg over 19.7 hours. Post Miller index, 9.7 (5.3) mm Hg
Liu et al, 2012²⁸	Doppler US, CT, and venography	CDT Low doses of urokinase and heparin for 1 week. Mean _______ At follow-up (6-24 months), CT, radiographic, and ultrasonographic findings were reexamined
Munakata et al, 2012²⁹	Diagnosis of PE confirmed with pulmonary angiography	CDT with urokinase (2.4-4.8 mg), tisokinase (14.4 mg), monteplase (0.6-1.6 mg)
Nassiri et al, 2012³⁰	CT angiographic evidence of PE Right-sided heart strain defined as troponin >0.01 ng/mL or echocardiographic findings of RV dilatation (RV: LV end-diastolic area >1.0)	AngioJet^c CDMT with or without adjunctive thrombolytic power-pulse spray. Mean dose of 29 mg of Alteplase (range: 20-37 mg) was administered during CDMT. Adjunctive alteplase
Kennedy et al, 2013³¹	Diagnosis of submassive or massive PE with pulmonary CT angiography or $\dot{V} / \dot{Q}$ scan Pre Sys PAP, 47 (15) mm Hg Pre PAP, 27 (9) mm Hg Pre Miller index, 25 (3) mm Hg	Anticoagulation and treatment with EkoSonic Endovascular System^b USAT infusion catheter administration of rtPA. Total dose of 35.1 ± 11.1 mg of r-TPA was administered over 19.6 ± 6.0 hours during treatment Post Sys PAP, 38 (12) mm Hg Post PAP, 20 (6) mm Hg Post Miller index, 17 (6) mm Hg
Akin et al, 2014³²	PE confirmed with CT of the chest or pulmonary arteriogram Preinterventional and postinterventional measures assessed: echocardiography, PAPs, cardiac biomarkers, tricuspid regurgitation, RV dilatation, and systolic function Pre PAP, 45.8 mm Hg (massive), 46.2 mm Hg (submassive)	Pronto^d extraction catheter and standard pigtail catheter Lytic therapy: rtPA Mean bolus dose of rtPA for patients with massive PE was 46 mg. The mean bolus dose for patients with submassive PE was 13.2 mg. The overall mean doses of rt-PA were 44 and 26 mg in massive and submassive PE, respectively Post PAP: 34.8 mm Hg (massive), 31.3 mm Hg (submassive)
Al-Hakim et al, 2014³³	PE in a hemodynamically stable patient (Sys blood pressure >90 mm Hg) with RV enlargement on CT (RV: LV >1) or decreased RV systolic function on echocardiogram	CDT lytic infusion with EkoSonic Endovascular System^b or by pigtail catheter with tPA (mean delivery of 20.0 mg tPA). Some received direct intraclot pulse tPA with a mean delivery of 23.7 mg tPA. Mechanical thrombectomy (pigtail rotation, AngioJet^c, aspiration)
Fernandez et al, 2014³⁴	Massive PE according to ACCP guidelines and confirmed with CT and Doppler US, moderate to severe RV failure Preprocedure Shock Index and PAP and Sys PAP before and after procedure Miller index was estimated after pulmonary angiography	AngioJet^c thrombectomy system. No fibrinolysis used.
Ivanauskiene et al, 2014³⁵	Acute massive PE with cardiogenic shock (Shock Index ≥1), or severe RV dysfunction Troponin and brain natriuretic peptide Pre Sys PAP, 57.9 (15.8) mm Hg Pre PAP, 34.3 (7.56) mm Hg	Percutaneous rheolytic thrombectomy with AngioJet Xpeedior^c catheter Selective thrombolysis (tPAs) with mean dose 30 mg. Post Sys PAP, 48.2 (14.76) mm Hg Post PAP, 28.9 (6.99) mm Hg
Quintana et al, 2014³⁶	Patients with acute symptoms and CT evidence of large thrombus burden and evidence of RV dysfunction or failure Follow-up with posttreatment echocardiography	Thrombolytic treatment in all patients with EkoSonic Endovascular system^b Thrombolytic agent: tPA. Median dose was 18.0 mg infused over 20.8 hours

Abbreviations: ACCP, American College of Chest Physicians; CDMT, catheter-directed mechanical thrombectomy; CDT, catheter-directed thrombolysis; CT, computed tomography; CTPA, computed tomographic pulmonary arteriography; LV, left ventricular; PAP, pulmonary artery pressure; PE, pulmonary embolism; PESI, Pulmonary Embolisms Severity Index; Post, follow-up (after thrombolysis); Pre, baseline (before thrombolysis); rtPA, recombinant tissue plasminogen activator; RV, right ventricular; Sys, systolic; tPA, tissue plasminogen activator; US, ultrasonography; USAT, ultrasound-accelerated thrombolysis; $\dot{V} / \dot{Q}$ , ventilation-perfusion.

^aValues are mean (SD) unless indicated otherwise.

^bEKOS Corp., Bothell, Washington.

^cBoston Scientific Corp., Natick, Massachusetts.

^dVascular Solutions, Inc., Minneapolis, MN.

Table 3 presents the pooled estimates of the efficacy and safety incidence rates. The risk of death in the 18 non-USAT studies was 9% (95% confidence interval [CI], 6%-13%); there was no significant heterogeneity for this mortality estimate (P = .12). In the 6 USAT studies with reported mortality, 4% of the patients died (95% CI, 1%-11%). We could not discriminate USAT data from non-USAT data in the study by Al-Hakim et al³³; thus, these results were reported separately.

Table 3.

Meta-Analysis of Studies: Use of Catheter-Directed Thrombolysis With and Without Ultrasound-Assisted Thrombolysis.

	Studies, No.	Incidence, %	95% CI, %	I ², %	P for Heterogeneity
CDT, no USAT
All bleeding events	18	10	5-20	77	.00
Risk of death	18	9	6-13	29	.12
Major bleeding	18	10	6-14	32	.10
Major complication	18	17	10-27	74	.00
Minor complication	18	6	2-13	68	.00
USAT and CDT
All bleeding events	1	6	1-31	NA	NA
Risk of death	1	3	0-31	NA	NA
Major bleeding	1	3	0-31	NA	NA
Major complication	1	3	0-31	NA	NA
Minor complication	1	11	3-35	NA	NA
USAT only
All bleeding events	5	12	7-20	0	.71
Risk of death	6^a	4	1-11	0	.85
Major bleeding	6^a	3	1-9	0	.96
Major complication	6^a	4	1-11	0	.85
Minor complication	5	12	7-20	0	.71

Abbreviations: NA, not applicable; USAT, ultrasound-accelerated thrombolysis.

^aOne study allowed separate data analysis for use of USAT versus no use of USAT.

Twelve studies used a formal PE stratification score. The most commonly used was the Miller index, reported in 10 studies. The average prethrombolysis Miller index was 19.4, and improvement was reported in all studies, with an average Miller index of 9.9 after the intervention. Pulmonary pressures were not consistently reported. Only 6 of 13 studies reported prethrombolysis mean pulmonary pressures; the average was 57 mm Hg. After the procedure, mean pulmonary pressure averaged 36 mm Hg.

In the 7 studies that reported a postintervention Miller index, there was improvement (Table 2); however, the data do not allow a pooled comparative analysis. Similarly, 6 of 13 studies reported systolic pulmonary artery pressures before and after the intervention. All reported improvement. None of the selected studies presented a quality-of-life evaluation. In addition, minor complications developed in 6% (95% CI, 2%-13%) of the patients in the non-USAT group and in 12% (95% CI, 7%-20%) in the USAT studies.

The main safety outcome was major bleeding. Among the 6 USAT studies, the incidence was 4% (95% CI, 1%-11%) compared to 10% (95% CI, 6%-14%) in studies that used alternative techniques. Secondary safety outcomes were all bleeding events, which occurred in 12% (95% CI, 7%-20%) of the USAT studies and in 10% (95% CI, 5%-20%) of the non-USAT studies.

Discussion

We report the best available evidence of the safety of modern endovascular treatment of PE. Although the risk of bleeding appears to be lower with USAT therapies, the heterogeneity between the trials and the paucity of adequate comparative data prevented us from reaching a definitive conclusion. The risk of death—as high as 9% despite advances in therapeutic techniques—stresses the need for further studies in this area.

In contrast to our results, Kuo et al¹² reported a meta-analysis with 594 patients in 35 studies before 2009. The pooled risk of major complications was 2.4% (95% CI, 1.9%-4.3%). None of the included studies evaluated USAT technology, and there were no comparative trials. We measured a similar rate of major complications for USAT compared to the 1 reported in the study by Kuo et al.¹² Engelberger and Kucher¹⁰ summarized the data from 197 patients with high-risk PE abstracted from 7 studies. That systematic review was restricted to USAT, and the mortality at 3 months was 3.6% (95% CI, 1.4%-7.2%), with major bleeding complications developing in 3.6% of the patients. The complication and mortality rates that we estimated for USAT were similar. From the available information, it is not possible to define superiority of USAT for PE revascularization. The best estimates for USAT may be derived from the Ultrasound Accelerated Thrombolysis of Pulmonary Embolism (ULTIMA) trial by Kucher et al,² in which 59 patients who had acute PE and a ratio of right ventricular dimension to left ventricular dimension of 1.0 or more were randomly assigned to receive heparin or USAT (n = 30). Only the USAT group had significant improvement in the ratio, with no measurable increase in bleeding complications. There is, however, no prospective, randomized comparison between USAT and CDT. The study by Lin et al¹⁷ retrospectively analyzed 25 patients with PE. The patients who received CDT and USAT had an improved Miller index, but no method was clearly superior.

Our study has potential limitations. We did not have a formal tool for measuring potential bias, this was a choice made given that the majority of the studies where noncomparative. Thus, the validated risk assessment tools were mostly inadequate for the type of publications. There was a great variation in the type and dose of thrombolytic. Although investigating this variable would have better explained our findings, this information was not sufficiently clarified in the manuscripts in order to create a pooled analysis.

Conclusions

We reviewed the best available estimate to date of using modern mechanisms of advanced PE therapy. Current clinical evidence does not prove USAT is superior over CDT methods.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Catheter-Directed Treatment of Pulmonary Embolism: A Systematic Review and Meta-Analysis of Modern Literature

Abstract

Keywords

Introduction

Methods

Statistical Analysis

Results

Discussion

Conclusions

Footnotes

Declaration of Conflicting Interests

Funding

References