Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry

doi:10.1378/chest.15-0119

CHEST

Volume 148, Issue 3, September 2015, Pages 667-673

https://doi.org/10.1378/chest.15-0119 Get rights and content

BACKGROUND

Systemic thrombolysis for acute pulmonary embolism (PE) carries up to a 20% risk of major bleeding, including a 2% to 5% risk of hemorrhagic stroke. We evaluated the safety and effectiveness of catheter-directed therapy (CDT) as an alternative treatment of acute PE.

METHODS

One hundred one consecutive patients receiving CDT for acute PE were prospectively enrolled in a multicenter registry. Massive PE (n = 28) and submassive PE (n = 73) were treated with immediate catheter-directed mechanical or pharmacomechanical thrombectomy and/or catheter-directed thrombolysis through low-dose hourly drug infusion with tissue plasminogen activator (tPA) or urokinase. Clinical success was defined as meeting all the following criteria: stabilization of hemodynamics; improvement in pulmonary hypertension, right-sided heart strain, or both; and survival to hospital discharge. Primary safety outcomes were major procedure-related complications and major bleeding events.

RESULTS

Fifty-three men and 48 women (average age, 60 years [range, 22-86 years]; mean BMI, 31.03 ± 7.20 kg/m²) were included in the study. The average thrombolytic doses were 28.0 ± 11 mg tPA (n = 76) and 2,697,101 ± 936,287 International Units for urokinase (n = 23). Clinical success was achieved in 24 of 28 patients with massive PE (85.7%; 95% CI, 67.3%-96.0%) and 71 of 73 patients with submassive PE (97.3%; 95% CI, 90.5%-99.7%). The mean pulmonary artery pressure improved from 51.17 ± 14.06 to 37.23 ± 15.81 mm Hg (n = 92) (P ≤ .0001). Among patients monitored with follow-up echocardiography, 57 of 64 (89.1%; 95% CI, 78.8%-95.5%; P≤.0001) showed improvement in right-sided heart strain. There were no major procedure-related complications, major hemorrhages, or hemorrhagic strokes.

CONCLUSIONS

CDT improves clinical outcomes in patients with acute PE while minimizing the risk of major bleeding. At experienced centers, CDT is a safe and effective treatment of both acute massive and submassive PE.

TRIAL REGISTRY

ClinicalTrials.gov; No.: NCT01097928; URL: www.clinicaltrials.gov

Section snippets

Results

Fifty-three men and 48 women (average age, 60 years [range, 22-86 years]; mean BMI, 31.03 ± 7.20 kg/m², consistent with an obese population) were included in the study. The baseline demographics and clinical characteristics are summarized in Table 1. Acute submassive PE and massive PE were observed in 73% (73 of 101) and 28% (28 of 101) of patients, respectively.

Discussion

The role of CDT for acute PE is rapidly evolving, and guidelines have acknowledged CDT as a viable treatment option for acute massive PE⁸ in patients who have (1) contraindications to thrombolysis, (2) failed thrombolysis, or (3) shock likely to cause death before systemic thrombolysis can take effect (eg, within hours) if appropriate expertise and resources are available. Nevertheless, large prospective studies are lacking, and the ideal CDT protocol, particularly for submassive PE, remains

Conclusions

To our knowledge, PERFECT is the first multicenter PE registry to demonstrate the clinical safety and effectiveness of CDT in a real-world population with acute PE. These data support an optimal CDT protocol of rapid clot debulking for massive PE that avoids using the AngioJet device to minimize procedure-related complications. These data also support the use of low-dose thrombolytic infusion through standard catheters for patients with submassive PE without the need for high-cost USAT

Acknowledgments

Author contributions: W. T. K. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. W. T. K. wrote the initial draft of the manuscript and revised subsequent drafts based on input from all coauthors and W. T. K., A. B., P. S. K., F. J. D., J. R. L., F. R. F., K. U., M. J. B., A. K. S., M. J. H., J. K. R., and M. A. D. G. vouched for the accuracy, completeness, and analysis of the reported data and agreed to

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Effectiveness and Safety of Large-Bore Aspiration Thrombectomy for Intermediate- or High-Risk Pulmonary Embolism
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To evaluate effectiveness and safety of large-bore mechanical thrombectomy of intermediate- or high-risk pulmonary embolism (PE) and factors associated with effectiveness.
A retrospective review of 257 patients with intermediate- or high-risk PE who underwent mechanical thrombectomy using the Flowtriever system (Inari Medical, Irvine, California) between July 2019 and November 2021 was conducted. Data were analyzed using the linear regression and Kaplan-Meier methods with a Type 1 error set at 0.05.
Patients’ mean age was 62 years, and 51% were male. PE risk was classified as high, intermediate-high, and intermediate-low in 37 (14%), 201 (78%), and 18 (7%) of the patients, respectively. Procedural technical success was 100%. The mean pulmonary artery pressure (MPAP) decreased from a mean of 32 mmHg (SD ± 9) before to 24 mmHg (SD ± 9) after thrombectomy (mean decrease, 8 mmHg [SD ± 6]; P < .0001). Immediate complications occurred in 2% of the patients. Postprocedural 30-day and all-time PE-attributable mortality in a mean of 1.3-year follow-up was 2% and 6%, respectively. In multivariate analysis, the presence of lower extremity DVT at presentation (β ± SE, −7.60 ± 3.22; P = .019) and a higher prethrombectomy MPAP (β ± SE, −0.19 ± 0.04; P < .001) were associated with lower degrees of decrease in MPAP in the intermediate-high–risk PE group. Among 14 patients with postthrombectomy PE-attributable mortality, 13 had postthrombectomy MPAPs of >20 mmHg.
Large-bore aspiration thrombectomy is a safe and effective treatment for reducing PAP in patients with intermediate- or high-risk PE. Postthrombectomy MPAPs of >20 mmHg might indicate postthrombectomy PE-attributable mortality in high-risk patients.
Intermediate-high risk pulmonary embolism: When teamwork really matters
2024, Thrombosis Update
Pulmonary embolism is a common disease associated with significant morbidity and mortality. Existing validated risk stratification tools have enabled the rapid identification of patients with low versus high-risk pulmonary embolism. Intermediate-high risk pulmonary embolism is defined as pulmonary embolism with haemodynamic stability, evidence of right ventricular dysfunction and elevated cardiac biomarkers. The therapeutic management of intermediate-high risk pulmonary embolism in the acute setting is challenging as these patients are often unwell, but do not fulfil criteria for high-risk pulmonary embolism. Although current guidelines recommend prompt first-line treatment with systemic anticoagulation and monitoring for deterioration, alternative strategies are being increasingly considered in this cohort. These include systemic or catheter-directed thrombolysis, surgical embolectomy, and mechanical circulatory support. In this case series, we discuss three cases of intermediate-high risk pulmonary embolism with a focus on multidisciplinary decision making in clinical management. Following on from this, we provide a brief narrative review of the current literature and guidelines surrounding this topic, considering the risks and benefits of alternative therapy options on patient outcomes.
Underuse of reperfusion therapy with systemic thrombolysis in high-risk acute pulmonary embolism in a Portuguese center
2024, Revista Portuguesa de Cardiologia
Reperfusion therapy is generally recommended in acute high-risk pulmonary embolism (HR-PE), but several population-based studies report that it is underused. Data on epidemiology, management and outcomes of HR-PE in Portugal are scarce.
To determine the reperfusion rate in HR-PE patients, the reasons for non-reperfusion, and how it influences outcomes.
In this retrospective cohort study of consecutive HR-PE patients admitted to a thromboembolic disease referral center between 2008 and 2018, independent predictors for non-reperfusion were assessed by multivariate logistic regression. PE-related mortality and long-term MACE (cardiovascular mortality, PE recurrence and chronic thromboembolic disease) were calculated according to the Kaplan–Meier method. Differences stratified by reperfusion were assessed using the log-rank test.
Of 1955 acute PE patients, 3.8% presented with hemodynamic instability. The overall reperfusion rate was 50%: 35 patients underwent systemic thrombolysis, one received first-line percutaneous embolectomy and one rescue endovascular treatment. Independent predictors of non-reperfusion were: age, with >75 years representing 12 times the risk of non-treatment (OR 11.9, 95% CI 2.7–52.3, p=0.001); absolute contraindication for thrombolysis (31.1%), with recent major surgery and central nervous system disease as the most common reasons (OR 16.7, 95% CI 3.2–87.0, p<0.001); and being hospitalized (OR 7.7, 95% CI 1.4–42.9, p=0.020). At a mean follow-up of 2.5 ± 3.3 years, the survival rate was 33.8%. Although not reaching statistical significance for hospital mortality, mortality in the reperfusion group was significantly lower at 30 days, 12 months and during follow-up (relative risk reduction of death of 64% at 12 months, p=0.013). Similar results were found for MACE.
In this population, the recommended reperfusion therapy was performed in only 50% of patients, with advanced age and absolute contraindications to fibrinolysis being the main predictors of non-reperfusion. In this study, thrombolysis underuse was associated with a significant increase in short- and long-term mortality and events.
A reperfusão é geralmente o tratamento recomendado no tromboembolismo pulmonar de alto risco (TEP-AR), embora vários estudos populacionais reportem a sua subutilização. Em Portugal, não existem dados sobre incidência, tratamento e eventos nesta população.
Estimar a taxa de reperfusão na população com TEP-AR, os motivos de não reperfusão (NR) e o seu impacto nos resultados clínicos destes doentes (dts).
Coorte retrospetiva de dts consecutivos com TEP-AR num centro de referência (2008 a 2018). Os preditores independentes de NR foram estudados através de regressão logística multivariada. As incidências de mortalidade relacionada com TEP e de MACE no seguimento (morte cardiovascular, recorrência de TEP e hipertensão pulmonar tromboembólica crónica) foram calculadas pelo método de Kaplan-Meier. As diferenças entre grupos de reperfusão foram estratificadas pelo teste log-rank.
De 1955 dts com TEP agudo, 3,8% apresentaram-se hemodinamicamente instáveis. A taxa de reperfusão total foi 50% - 35 dts com trombólise sistémica, 1 dt com embolectomia percutânea primária e 1 dt com tratamento endovascular de recurso. Os preditores independentes de NR foram: idade, ter > 75 anos associou-se a 12 vezes mais risco de NR (OR 11,9, 95%CI 2,7-52,3, p=0,001); contraindicações absolutas para trombólise (31,1%), sendo a cirurgia major recente e a doença do sistema nervoso central as causas mais comuns (OR 16,7, IC95% 3,2-87,0, p<0,001); estar hospitalizado (OR 7,7, 95%CI 1,4-42,9, p=0,020). Com um seguimento médio de 2,5±3,3 anos, a sobrevida foi de 33,8%. Apesar de o impacto na mortalidade intra-hospitalar não ter atingido significado estatisticamente significativo. O grupo da reperfusão mostrou uma melhoria significativa da mortalidade aos 30 dias, 12 meses e no seguimento (com uma redução de risco relativo de 64% na mortalidade a 12 meses, p=0,013). Os resultados na redução de MACE foram semelhantes.
Na população analisada, a terapêutica recomendada de reperfusão foi registada em apenas 50% dos doentes, sendo a idade avançada e a presença de contraindicações absolutas para fibrinólise os principais preditores de não tratamento. Neste estudo, a subutilização de trombólise associou-se a um aumento significativo de mortalidade e eventos cardiovasculares a curto e longo prazo.
Catheter-directed therapy for acute pulmonary embolism: results of a multicenter national registry
2024, Revista Espanola de Cardiologia
El emergente tratamiento por catéter (TPC) de la embolia pulmonar (EP) aguda combina técnicas heterogéneas. El objetivo del estudio es describir la práctica clínica contemporánea y los resultados relacionados con la TPC en un registro de ámbito nacional.
Registro multicéntrico iniciado por investigador, destinado a incluir a pacientes con EP aguda consecutivos y en riesgo intermedio-alto (IAR) o alto riesgo (AR) elegibles para TPC. El resultado primario del estudio fue la muerte por cualquier causa en el hospital.
Se incluyó en total a 253 pacientes, 93 (36,8%) con EP-AR y 160 (63,2%) con EP-IAR, de una media de edad de 62,3 ± 15,1. Se realizó trombolisis local al 70,8% de los pacientes, trombectomía aspirativa al 51,8% y ambas al 23,3%. Sin embargo, la trombectomía por aspiración fue más frecuente en la cohorte de EP-AR (el 80,6 frente al 35%; p < 0,001). Solo 51 pacientes (20,2%) se sometieron a TPC con dispositivos específicos de EP. El éxito de la TPC fue del 90,9% (el 98,1% de los casos de EP-IAR frente al 78,5% de los de EP-AR; p < 0,001). La mortalidad hospitalaria fue del 15,5%, muy concentrada en los casos de EP-AR (37,6%) y significativamente menor entre los de EP-IAR (2,5%; p < 0,001). La mortalidad a largo plazo (24 meses) fue del 40,2 en EP-AR frente al 8,2% en EP-IAR (p < 0,001).
A pesar del elevado éxito de la TPC, la mortalidad hospitalaria por EP-AR sigue siendo alta (37,6%) respeto a la muy baja mortalidad de la EP-IAR (2,5%).
Catheter-directed therapy (CDT) for acute pulmonary embolism (PE) is an emerging therapy that combines heterogeneous techniques. The aim of the study was to provide a nationwide contemporary snapshot of clinical practice and CDT-related outcomes.
This Investigator-initiated multicenter registry aimed to include consecutive patients with intermediate-high risk (IHR) or high-risk (HR), acute PE eligible for CDT. The primary outcome of the study was in-hospital all-cause death.
A total of 253 patients were included, of whom 93 (36.8%) had HR-PE, and 160 (63.2%) had IHR-PE with a mean age of 62.3 ± 15.1 years. Local thrombolysis was performed in 70.8% and aspiration thrombectomy in 51.8%, with 23.3% of patients receiving both. However, aspiration thrombectomy was favored in the HR-PE cohort (80.6% vs 35%; P < .001). Only 51 patients (20.2%) underwent CDT with specific PE devices. The success rate for CDT was 90.9% (98.1% of IHR-PE patients vs 78.5% of HR-PE patients, P < .001). In-hospital mortality was 15.5%, and was highly concentrated in the HR-PE patients (37.6%) and significantly lower in IHR-PE patients (2.5%), P < .001. Long-term (24-month) mortality was 40.2% in HR-PE patients vs 8.2% in IHR-PE patients (P < .001).
Despite the high success rate for CDT, in-hospital mortality in HR-PE is still high (37.6%) compared with very low IHR-PE mortality (2.5%).
Treatment of acute pulmonary embolism after catheter-directed thrombolysis with dabigatran vs warfarin: results of a multicenter randomized RE-SPIRE trial
2024, Journal of Vascular Surgery: Venous and Lymphatic Disorders
Thrombolytic therapy is effective method in the high-risk acute pulmonary embolism (PE) treatment. Reduced-dose thrombolysis (RDT) plus oral anticoagulation therapy is effective and safe method in the moderate and severe PE treatment. It is leading to good early and intermediate-term outcomes. In the RE-COVER and RE-COVER II studies, dabigatran showed similar effectiveness as warfarin in the treatment of acute PE. Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the prevention of PE after mechanical fragmentation and RDT (catheter-directed treatment [CDT]+RDT) in patients with high and intermediate to high PE risk. We sought to evaluate the efficacy and safety (incidence of clinically significant recurrence of venous thromboembolic complications and deaths) during a 6-month course of treatment with dabigatran or warfarin in patients with high and intermediate to high acute PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT).
The RE-SPIRE is a prospective, multicenter randomized double-arm study. Over a 5-year period, 66 consecutive patients with symptomatic high and intermediate to high PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT) were randomized into two groups within the next 48 hours. The first group continued treatment with dabigatran 150 mg twice a day for 6 months; the second group continued treatment with warfarin under the control of international normalized ratio (2.0-3.0) for 6 months. Both groups received low molecular weight heparins for 2 days after surgery. Then, group 1 continued to receive low molecular-weight-heparin for 5 to 7 days, followed by a switch to dabigatran at a dosage of 150 mg two times a day. Group 2 received both low-molecular-weight heparin and warfarin up to an international normalized ratio of >2.0, followed by heparin withdrawal. The follow-up period was 6 months.
There were 63 patients who completed the study (32 in the dabigatran group and 31 in the warfarin group). In both groups, there was a statistically significant decrease in the mean pulmonary artery pressure. The mean pulmonary artery pressure at the 6-month follow-up after surgery was 24 mm Hg (interquartile range, 20.3-29.25 mm Hg) in the dabigatran group and 23 mm Hg (interquartile range, 20.0-26.3 mm Hg) in the warfarin group. The groups did not differ statistically in the deep vein thrombosis dynamics. Partial recanalization occurred in 52.0% vs 73.1% in the dabigatran and warfarin groups, respectively (P = .15). Complete recanalization occurred in 28.0% vs 19.2% in the dabigatran and warfarin groups, respectively (P = .56). The groups did not differ in the frequency of major bleeding events according to the International Society for Thrombosis and Hemostasis (0% vs 3.2% in the dabigatran and warfarin groups, respectively; P = 1.00). However, there were more nonmajor bleeding events in the warfarin group than in the dabigatran group (16.1% vs 0%, respectively; P = .02).
The results of the study show that dabigatran is comparable in effectiveness to warfarin. Dabigatran has greater safety in comparison with warfarin in the occurrence of all cases of bleeding in the postoperative and long-term periods. Thus, dabigatran may be recommended for the treatment and prevention of PE after CDT with RDT in patients with high and intermediate to high PE risk.
Implementing a Pediatric Pulmonary Embolism Response Team Model: An Institutional Experience
2024, Chest
Pulmonary embolism is increasing in prevalence among pediatric patients; although still rare, it can create a significant risk for morbidity and death within the pediatric patient population. Pulmonary embolism presents in various ways depending on the patient, the size of the embolism, and the comorbidities. Treatment decisions are often driven by the severity of the presentation and hemodynamic effects; severe presentations require more invasive and aggressive treatment. We describe the development and implementation of a pediatric pulmonary embolism response team designed to facilitate rapid, multidisciplinary, data-driven treatment decisions and management.

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originally published Online First April 9, 2015.

Part of this article has been presented in abstract form at the Cardiovascular and Interventional Radiological Society of Europe Annual Scientific Meeting, September 13-17, 2014, Glasgow, Scotland.

FUNDING/SUPPORT: This study was funded by the Stanford Division of Vascular and Interventional Radiology.

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CHEST

Original ResearchPulmonary Vascular DiseasePulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

TRIAL REGISTRY

Section snippets

Results

Discussion

Conclusions

Acknowledgments

Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis

JAMA

Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism

Circulation

Endovascular therapy for acute pulmonary embolism

J Vasc Interv Radiol

Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques

J Vasc Interv Radiol

Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography

J Am Soc Echocardiogr

Society of Interventional Radiology clinical practice guidelines

J Vasc Interv Radiol

Original Research
Pulmonary Vascular Disease
Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry