From anticoagulation to intervention: The expanding role of percutaneous therapies in pulmonary embolism

Abstract

Pulmonary embolism remains a major cause of cardiovascular morbidity and mortality, with management guided by risk stratification and the balance between thrombotic burden, right ventricular dysfunction and bleeding risk. Although anticoagulation remains the cornerstone of therapy, percutaneous catheter-based interventions have emerged as important alternatives or adjuncts in selected intermediate-risk and high-risk patients, particularly when systemic thrombolysis is contraindicated, has failed, or carries an unacceptable bleeding risk. These approaches include catheter-directed thrombolysis, ultrasound-assisted thrombolysis, mechanical thrombectomy, aspiration embolectomy and hybrid techniques, all aiming to achieve rapid hemodynamic improvement while limiting systemic thrombolytic exposure. Available trial and registry data suggest favorable effects on right ventricular function and pulmonary hemodynamics, with an acceptable safety profile in experienced centers, although recent comparative evidence for hard clinical endpoints remains limited. This review summarizes the current evidence, technical considerations and patient-selection principles for percutaneous therapies in acute pulmonary embolism and discusses their potential integration into evolving treatment algorithms and future research directions.

Key Words: Pulmonary embolism; Percutaneous interventions; Catheter-directed thrombolysis; Mechanical thrombectomy; Aspiration embolectomy; Endovascular therapy; Risk stratification; Bleeding risk

Core Tip: Pulmonary embolism remains a leading cause of cardiovascular mortality, and optimal management, particularly in intermediate-risk and high-risk patients, continues to evolve. This review critically appraises the expanding role of percutaneous catheter-based therapies, including catheter-directed thrombolysis and mechanical thrombectomy, as alternatives or adjuncts to systemic thrombolysis and anticoagulation. We synthesize contemporary randomized and registry data, discuss patient selection and procedural strategy and examine the emerging concept of a “primary percutaneous pulmonary intervention” approach as a potential paradigm shift in acute pulmonary embolism care.

INTRODUCTION

Pulmonary embolism (PE) remains the third leading cause of cardiovascular mortality worldwide, preceded only by myocardial infarction and stroke. Although PE carries a substantial burden of morbidity and mortality, therapeutic innovation in this field has historically progressed more slowly than in other major cardiovascular conditions, particularly acute coronary syndromes and ischemic stroke. Nevertheless, the past decade has been marked by major advances in PE management, including refinement of prognostic stratification tools, wider use of catheter-based reperfusion therapies and growing application of mechanical circulatory support in patients with severe hemodynamic compromise. At the same time, evidence from large registries and ongoing multicenter randomized studies evaluating catheter-directed interventions is rapidly expanding and may substantially influence future treatment algorithms for acute PE[1-3].

Reducing the clinical impact of PE requires a comprehensive strategy that includes prevention, timely diagnosis, accurate risk assessment and appropriate therapeutic selection. Therapeutic management is guided primarily by the estimated risk of early death. Current guidelines classify patients with hemodynamic instability as high risk, whereas hemodynamically stable individuals are stratified using clinical variables, imaging findings, laboratory biomarkers and relevant comorbidities that influence prognosis[2]. Anticoagulation remains the cornerstone of acute PE treatment across all risk categories. However, therapeutic strategies are rapidly evolving with the introduction of novel pharmacological agents and interventional approaches that have shown encouraging results in selected populations, expanding the therapeutic armamentarium for both treatment and prevention[4].

Acute PE results in abrupt obstruction of the pulmonary arterial vasculature together with release of vasoactive mediators, producing a sudden rise in pulmonary vascular resistance. Because the right ventricle (RV) is structurally adapted to a low-pressure circulation, this acute afterload increase leads to RV dilation, elevated wall stress and impaired coronary perfusion, eventually precipitating myocardial ischemia. Progressive RV enlargement displaces the interventricular septum toward the left ventricle (LV), thereby impairing LV filling and reducing systemic cardiac output. This hemodynamic deterioration may progress to systemic hypotension, cardiogenic shock and ultimately circulatory collapse. The sequence of these pathophysiologic events represents a central mechanism of mortality in severe PE. Consequently, increasing attention has been directed toward therapies capable of rapidly unloading the RV and preventing progression to obstructive shock[5,6].

To address these limitations, a range of percutaneous catheter-based therapies has been developed. These approaches either prevent embolic migration from the venous system through the use of vena cava filters or directly treat pulmonary arterial thrombi via venous catheter access. Available techniques include catheter-directed delivery of low-dose thrombolytic agents, with or without ultrasound assistance, as well as mechanical methods such as thrombus fragmentation, aspiration, or direct clot extraction. Reported procedural success rates approach 87%, with evidence suggesting lower mortality equated with systemic thrombolysis[7-10].

In this review, we discuss the contemporary management of PE, with particular emphasis on the expanding role of catheter-based reperfusion therapies. We summarize current approaches to risk stratification and patient selection, review the technical principles and available devices for catheter-directed thrombolysis (CDT) and mechanical thrombectomy and critically appraise the existing evidence from clinical trials and registries. In addition, we examine practical considerations, procedural complications, ongoing clinical studies and future directions that may further define the role of percutaneous intervention in the treatment of PE (Figure 1).

Figure 1 Interventional treatment of pulmonary embolism. Schematic overview of contemporary therapeutic strategies for acute pulmonary embolism. Management options span four principal domains: (1) Pharmaceutical therapy, including systemic anticoagulation and thrombolytic drug administration; (2) Surgical thrombectomy, involving open embolectomy under cardiopulmonary bypass in selected high-risk patients; (3) Catheter-directed therapies, such as catheter-directed thrombolysis, ultrasound-assisted thrombolysis, mechanical thrombectomy, thrombus fragmentation/rotational thrombectomy and rheolytic thrombectomy; and (4) Aspiration embolectomy, performed using large-bore catheter systems for direct clot extraction. These approaches aim to restore pulmonary perfusion, reduce right ventricular afterload and improve hemodynamic stability, with technique selection guided by patient risk stratification, bleeding risk and institutional expertise. The images were created using BioRender (Supplementary material).

MECHANICAL PROLEPSIS OF PE: CONTEMPORARY ROLE OF INFERIOR VENA CAVA FILTERS

Prolepsis of PE remains a fundamental component of venous thromboembolism (VTE) [encompassing deep vein thrombosis (DVT) and PE] management, particularly in patients at high risk for recurrent embolic events or in those with contraindications to anticoagulation. Although systemic anticoagulation represents the primary preventive strategy, mechanical approaches such as inferior vena cava (IVC) filter implantation may provide an alternative mean of preventing thrombus migration to the pulmonary circulation in carefully selected patients. Advances in device technology and retrieval techniques have expanded the clinical use of IVC filters, while ongoing debate persists regarding their long-term efficacy, complications and optimal indications.

VTE is closely linked to temporary hospital admission and prolonged immobility, most commonly in the setting of major surgery or severe trauma. Together, these conditions account for roughly 6 out 10 of all VTE events. The risk of VTE is markedly higher in hospitalized individuals, exceeding that of non-hospitalized populations by more than two orders of magnitude, while, among community cases, active malignancy contributes to nearly one fifth of incident events[1,11].

Patients with a particularly high risk of VTE, as well as those who cannot receive anticoagulation may be examined for intervention in the IVC. This strategy involves percutaneous placement of a filter designed to mechanically prevent venous thrombi from reaching the pulmonary circulation.

CONTEMPORARY MANAGEMENT OF ACUTE PE

Management of acute PE requires a structured therapeutic approach based on early risk stratification, hemodynamic status and bleeding risk assessment. While anticoagulation remains the cornerstone of treatment across all risk categories, patients with high-risk or selected intermediate-high-risk PE may require escalation to reperfusion therapies to rapidly restore pulmonary perfusion and prevent RV failure. Contemporary treatment options include systemic thrombolysis, surgical embolectomy and an expanding range of catheter-directed interventions, each associated with distinct indications, advantages and procedural considerations. Careful patient selection and multidisciplinary decision-making are therefore essential to optimize outcomes and minimize treatment-related complications.

Hemodynamic and prognostic assessment in PE

Appropriate risk stratification is a cornerstone of acute PE management, as both prognosis and treatment selection are closely linked to the degree of hemodynamic impairment and RV involvement. Patients presenting with high-risk PE, defined by obstructive shock or cardiopulmonary arrest, continue to experience substantial mortality despite advances in contemporary care, with registry data reporting mortality rates between 21% and 42%. In this setting, urgent reperfusion therapy, most commonly systemic thrombolysis, is generally required to rapidly relieve pulmonary arterial obstruction and restore circulatory stability[12].

By contrast, intermediate-risk PE comprises a broad and clinically diverse group of patients. Although systemic hypotension is absent, evidence of RV dysfunction identifies individuals at increased risk for early clinical deterioration and adverse outcomes. Intermediate-low-risk PE is typically characterized by either imaging evidence of RV dysfunction or elevated cardiac biomarkers, whereas intermediate-high-risk PE requires the coexistence of both abnormalities. Importantly, considerable variability in prognosis exists even within established risk categories. Commonly applied clinical prediction tools, such as the PE Severity Index, are effective in identifying low-risk patients suitable for conservative treatment. However, their ability to discriminate which intermediate-risk patients may deteriorate and require escalation of therapy remains limited. Therefore, refinement of current risk assessment strategies remains a key area of ongoing investigation in PE care.

Current guideline definitions of high-risk PE are largely based on the presence of systemic hypotension or vasopressor dependence. Nevertheless, some normotensive patients demonstrate evidence of occult hemodynamic compromise, with reduced cardiac output and tissue hypoperfusion despite preserved blood pressure. These observations suggest that significant circulatory dysfunction may precede overt hypotension and that selected patients with concealed hemodynamic instability could potentially benefit from earlier reperfusion strategies. Although additional studies are needed, identification of occult shock may facilitate a more individualized and physiology-driven approach to PE risk assessment beyond traditional categorical classification models[13,14].

In clinical practice, selection of the optimal reperfusion strategy requires careful assessment of both disease severity and bleeding risk. Systemic thrombolysis remains the recommended first-line reperfusion therapy for patients with high-risk PE presenting with hemodynamic instability, provided there are no absolute contraindications. However, catheter-directed therapies may be considered in high-risk patients when systemic thrombolysis is contraindicated, when the risk of major bleeding is deemed excessive, or when thrombolytic therapy has failed to achieve hemodynamic stabilization.

In intermediate-high-risk PE, defined by RV dysfunction and elevated cardiac biomarkers in the absence of systemic hypotension, the role of catheter-based interventions remains more individualized. These techniques may be considered in patients with evidence of clinical deterioration, large central thrombus burden, worsening RV dysfunction, or elevated bleeding risk with systemic thrombolysis. Treatment decisions in such scenarios should ideally be made within a multidisciplinary PE Response Team (PERT) framework, allowing integration of clinical presentation, imaging findings, comorbidities and institutional expertise.

Thrombolytic therapy, administered systemically or delivered directly into the pulmonary arteries via a catheter, can re-establish pulmonary blood flow, reduce right ventricular afterload and enhance aeration, as well as global hemodynamics. The role of systemic or CDT in other risk categories, however, remains less clearly defined[15].

Systemic thrombolysis

Systemic thrombolysis remains the conventional reperfusion therapy for patients with high-risk PE, particularly in the setting of hemodynamic instability or cardiogenic shock. By promoting rapid fibrinolysis and restoration of pulmonary blood flow, systemic thrombolytic therapy has been associated with reductions in PE-related mortality and hemodynamic collapse compared with anticoagulation alone. Nevertheless, its use is limited by a substantial risk of bleeding complications, including major hemorrhage and intracranial bleeding, which has restricted its broader adoption in clinical practice, especially among elderly patients and those with significant bleeding risk factors[16,17].

The role of systemic thrombolysis in intermediate-risk PE remains controversial. Although studies such as PEITHO demonstrated a reduction in hemodynamic decompensation, this benefit was not accompanied by improved short-term or long-term survival and was offset by significantly increased bleeding complications[18]. As a result, contemporary management strategies increasingly emphasize individualized risk assessment and careful patient selection. Reduced-dose thrombolytic regimens have shown promising safety profiles in selected patients, while emerging catheter-based reperfusion technologies are being explored as potential alternatives capable of achieving effective thrombus removal with lower bleeding risk. Ongoing randomized controlled trials (RCTs) are expected to further clarify the optimal role of systemic thrombolysis within the evolving therapeutic landscape of acute PE[19].

Surgical embolectomy

Surgical embolectomy represents a definitive reperfusion strategy for acute PE and remains an essential therapeutic option in carefully selected patients with severe disease. Historically reserved for critically ill patients because of high perioperative mortality, advances in surgical expertise, cardiopulmonary bypass techniques and perioperative critical care have substantially improved outcomes over recent decades. Contemporary surgical embolectomy is most commonly considered in patients with high-risk PE who have contraindications to systemic thrombolysis, failed thrombolytic therapy, or large central thrombus burden associated with impending hemodynamic collapse[20].

Progress in the operative approaches, perioperative care and patient prerogative have led to a progressive reduction in surgical morbidity and mortality. As a result, indications have broadened to include selected patients with less serious PE[21]. Surgical embolectomy is particularly considered in the presence of a large central thrombus burden, thrombus in transit, paradoxical embolism, or persistent hemodynamic instability. In these settings, surgery can achieve improvements in RV function comparable to thrombolysis, with similar short-term mortality and long-term survival.

Despite these favorable developments, surgical embolectomy remains a highly invasive intervention that requires specialized surgical expertise and carries inherent risks, including bleeding, infection and perioperative hemodynamic compromise. Consequently, it is generally reserved for cases in which alternative treatment strategies are contraindicated or ineffective and when the anticipated benefits outweigh procedural risks.

Catheter-directed therapies

Percutaneous catheter-based interventions have emerged as attractive alternatives to anticoagulation, systemic thrombolysis and surgery, owing to their minimally invasive nature and potentially improved safety profile. These endovascular techniques are designed to disrupt, fragment, or remove obstructive thrombi, or to deliver reduced doses of thrombolytic agents directly into the pulmonary arteries, thereby limiting systemic exposure and bleeding risk. Complete thrombus clearance is not always required. Instead, the principal objective is hemodynamic stabilization. Aggressive attempts at full clot removal may increase the likelihood of complications, including contrast-induced nephropathy, vascular access injuries, pulmonary artery trauma, or device-related adverse events (Table 1)[22]. Patient selection for catheter-based intervention should therefore be individualized and guided by hemodynamic status, RV dysfunction, thrombus burden, bleeding risk and the availability of experienced multidisciplinary teams.

Table 1 Contemporary catheter-based options for acute pulmonary embolism.

Device/system	Primary mechanism	Key technical characteristics	Typical venous access	PE indication status	Main advantages	Main limitations/risks
Pigtail catheters/peripheral balloon catheters	Mechanical clot disruption (fragmentation ± balloon maceration)	Small profile catheters (historically used); manual rotation over a wire; can be paired with local lytic infusion	Femoral or jugular	Not applicable	Simple, widely available, low cost; may provide rapid partial recanalization as a bridge	Fragmentation can push clot distally and potentially worsen obstruction; largely replaced by dedicated systems
Cragg-McNamara infusion catheter (Medtronic)	CDT	Multi-side-hole infusion catheter; multiple working lengths and infusion segments	Femoral	Yes	Dedicated infusion design; reliable local delivery without need for complex mechanical components	Requires prolonged infusion (commonly 12-24 hours); bleeding risk still present
Fountain infusion catheter (Merit Medical)	CDT	Multi-side-hole infusion system; variable infusion lengths	Femoral	No	Practical and relatively cost-efficient	Less robust PE-specific clinical evidence compared with some alternatives
Uni-Fuse (AngioDynamics)	CDT	Multi-side-hole infusion catheter; multiple infusion segment lengths	Femoral	Yes	Broad and uniform thrombolytic dispersion through side holes	Requires monitored infusion over many hours; bleeding risk persists
Pulse-spray infusion catheter (AngioDynamics)	CDT (pulsed delivery)	Side-hole catheter allowing bolus/pulsed lytic administration; can be used with fragmentation	Femoral	No	Can enhance drug penetration and shorten initial delivery phase	Limited PE-specific outcome data; still requires thrombolytic exposure
Bashir catheter (Thrombolex)	Hybrid: Mechanical clot disruption + local lytic delivery	Expandable basket with multiple micro-infusion points to distribute lytic within thrombus	Femoral	No	Multi-point drug delivery directly inside thrombus; may improve penetration	Limited clinical dataset and adoption; still involves thrombolytic use
EkoSonic (Boston Scientific)	Ultrasound-assisted CDT (USAT)	Dual-lumen catheter: Ultrasound core + thrombolytic infusion lumen; multiple treatment-zone lengths	Femoral or jugular	Yes	Ultrasound energy may loosen fibrin architecture, improving lytic penetration; allows lower-dose/shorter regimens	Higher cost; incremental clinical advantage vs standard CDT remains debated
Aspirex (Becton Dickinson)	Mechanical fragmentation + aspiration	Aspiration catheter designed for thrombus extraction (more often peripheral use)	Femoral	Yes, in European Union, not in United States	Straightforward concept; avoids systemic thrombolysis	May be less effective for organized/older thrombus; PE-specific evidence limited
AngioJet (Boston Scientific)	Rheolytic thrombectomy ± “power pulse” lytic injection	High-pressure saline jets fragment thrombus and create suction (Bernoulli effect); can be combined with local lytic injection	Femoral or jugular	Yes, in European Union; FDA boxed warning for PE	Rapid debulking with option for pharmacomechanical approach	Bradyarrhythmias, hemolysis, hemodynamic instability; safety concerns led to boxed warning in the United States
AngioVac (AngioDynamics)	Aspiration with extracorporeal veno-venous bypass	Large-bore aspiration cannula connected to external filtration and reinfusion circuit; requires perfusion support	Femoral + jugular (dual access)	No	Allows aspiration with reinfusion and limited net blood loss; useful for RA/IVC thrombus	Not designed for pulmonary artery thrombectomy; requires perfusion team; limited role in acute PE
AlphaVac (AngioDynamics)	Large-bore aspiration without extracorporeal support	Manual aspiration system; no bypass circuit; deliverable cannula with multiple configurations	Femoral or jugular	No	Avoids perfusion team; less complex than AngioVac	Clinical experience still limited; not established for chronic PE
FlowTriever (Inari Medical)	Large-bore aspiration ± mechanical extraction	Large aspiration catheters; nitinol mesh discs for clot engagement; optional blood filtration/reinfusion (FlowSaver)	Femoral or jugular	Yes	Effective for high clot burden; avoids thrombolytics; strong prospective trial and registry evidence	Large and relatively stiff system can limit distal branch reach; requires operator experience
Indigo aspiration system (Penumbra)	Aspiration + mechanical thrombus disruption	Continuous suction pump + separator wire; smaller, more flexible catheters; optional Lightning Suction-Control Technology	Femoral or jugular	Yes	Better navigation into distal pulmonary branches; automated suction control may reduce blood loss	No blood reinfusion/filtering; effectiveness may be lower for highly organized clot

CDT: Catheter-directed thrombolysis; USAT: Ultrasound-assisted thrombolysis; FDA: Food and Drug Administration; PE: Pulmonary embolism; RA: Right atrium; IVC: Inferior vena cava.

Catheter-directed approaches are particularly suited for high-risk patients who are ineligible for systemic thrombolysis or who have not responded adequately to it. Selection of the most appropriate technique depends on several factors, including the patient’s clinical status, operator expertise, institutional resources and thrombus location and extent within the pulmonary arterial tree. Reported procedural success, typically defined as hemodynamic stabilization, improvement in oxygenation and survival to hospital discharge, approaches 87%, with relatively low rates of major bleeding, including rare intracranial hemorrhage and modest rates of major extracranial bleeding or vascular injury[23]. However, robust evidence from large RCTs remains limited.

ENDOVASCULAR REPERFUSION STRATEGIES FOR PE

Endovascular treatment options for PE include CDT and various forms of mechanical thrombectomy, such as thrombus fragmentation, rotational and rheolytic thrombectomy, and aspiration embolectomy (Table 2).

Table 2 Expected complications of catheter-based therapies for acute pulmonary embolism.

Complication	Approximate frequency	Likely mechanism/trigger	Practical management
Acute hemodynamic decompensation (sudden hypotension/collapse)	Uncommon	Distal embolization after clot fragmentation increasing pulmonary vascular resistance; RV strain from prolonged catheter manipulation; arrhythmia or acute RV failure during intervention	Escalate vasopressors/inotropes; terminate or simplify catheter maneuvers; consider rescue thrombolysis if appropriate; mechanical support (e.g., VA-ECMO) when refractory
Mechanical injury to the tricuspid valve	Uncommon	Inadvertent aggressive valve crossing or repeated catheter passes causing acute tricuspid regurgitation or leaflet/chordal damage	Remove/withdraw catheter; echocardiographic evaluation; cardiac surgical consultation if severe structural injury
Cardiac perforation with pericardial tamponade	Rare	Guidewire or catheter perforation (RA/RV) during manipulation	Immediate pericardiocentesis; hemodynamic stabilization; surgical repair if persistent bleeding
Hemoptysis/pulmonary hemorrhage	Uncommon	Pulmonary artery branch injury (wire perforation or catheter trauma); reperfusion injury after rapid flow restoration; thrombolysis-related bleeding	Airway protection and ventilatory support (selective intubation if needed); stop/limit thrombolytics; reverse anticoagulation when required; endovascular measures (balloon tamponade, selective coiling) in focal injury
Pulmonary artery dissection (large branch)	Rare	Excessive catheter torque, stiff wire trauma, or device advancement in tortuous anatomy	Often conservative monitoring if stable; balloon angioplasty if flow-limiting; CTA follow-up when indicated
Systemic (paradoxical) embolization	Rare	Embolus passage through intracardiac shunt (e.g., PFO) or other right-to-left communication	Treat based on embolic territory (stroke/limb/visceral); multidisciplinary management; consider evaluation for shunt closure after stabilization
Non-pulmonary major bleeding	Uncommon	Thrombolytic exposure (CDT/USAT), excessive anticoagulation, or access-site bleeding	Stop thrombolysis; reverse heparin if necessary; manage bleeding source specifically (GI, GU, retroperitoneal, etc.)
Hemolysis and bradyarrhythmias (device-related)	Uncommon (device-dependent)	Mainly described with rheolytic systems (e.g., AngioJet): Hemolysis-mediated release of vasoactive mediators	Limit activation time; monitor rhythm closely; treat bradycardia/AV block; discontinue device if instability occurs
Vascular access complications (hematoma, pseudoaneurysm, venous injury)	Uncommon	Large-bore sheaths (especially thrombectomy platforms), inadequate ultrasound guidance, prolonged procedure	Ultrasound-guided access; closure/pressure; transfusion if needed; vascular surgery/interventional radiology when severe
Contrast-associated acute kidney injury	Uncommon	High contrast volume in unstable patients or baseline CKD	Minimize contrast; hydration if feasible; avoid nephrotoxins; monitor creatinine

RV: Right ventricle; RA: Right atrium; PFO: Patent foramen ovale; CDT: Catheter-directed thrombolysis; USAT: Ultrasound-assisted thrombolysis; CKD: Chronic kidney disease; VA-ECMO: Venoarterial extracorporeal membrane oxygenation; CTA: Computed tomography angiography; GI: Gastrointestinal; GU: Genitourinary; AV: Atrioventricular.

CDT

CDT involves the placement of a catheter, most commonly a dedicated multi-side-hole infusion catheter, though pigtail catheters may also be used, into the affected pulmonary arteries to deliver low-dose thrombolytic agents directly into the thrombus. This targeted approach increases the surface area of clot exposed to fibrinolytics while reducing preferential blood flow to unobstructed lung segments. Mechanical fragmentation of the thrombus may be performed before or during drug infusion to further enhance thrombolytic penetration and accelerate hemodynamic improvement. By using substantially lower drug doses than systemic thrombolysis, CDT seeks to preserve efficacy while minimizing bleeding risk[24]. Among percutaneous strategies, CDT is also associated with comparatively lower procedural costs.

Vascular access is typically obtained under ultrasound guidance. When bilateral pulmonary artery treatment is required, a second venous access may be established. Commonly used infusion systems include the Uni-Fuse, Cragg-McNamara and Pulse-Spray catheters, all of which feature side holes for drug delivery. The Bashir catheter differs by incorporating a distal expandable basket composed of multiple micro-infusion elements, allowing dispersion of thrombolytic agents within the clot. These devices are intended for intravascular delivery of fluids, including thrombolytics and contrast media[25,26].

Following catheter placement, an initial bolus of thrombolytic agent is administered, followed by continuous infusion. Although protocols vary between centers, alteplase is commonly infused at 0.5-1 mg per hour per catheter, with a total dose generally limited to 30 mg over 12-24 hours under close monitoring. Upon completion, catheters and sheaths are often removed at the bedside without repeat imaging. Treatment is discontinued if major bleeding occurs or if clear hemodynamic improvement is achieved. In unstable patients, the aim of CDT is risk reduction rather than complete clot eradication, with the goal of transitioning from high-risk to intermediate-risk PE.

Ultrasound-assisted thrombolysis

An evolution of standard CDT is ultrasound-assisted thrombolysis (UATh). The EkoSonic system consists of a dual-lumen catheter, one housing ultrasound transducers that generate pulsed, no-high-intensity waves, while the rest enable the thrombolytic delivery. Ultrasound energy is thought to disrupt fibrin architecture, increasing drug penetration by exposing additional binding sites[27].

Compared with conventional CDT, UATh is more costly but allows enhanced thrombolytic efficacy at lower doses and over shorter infusion times. Different catheter sizes are available, including higher-power versions designed to further augment clot lysis. UATh has been assessed in RCTs and prospective registries and has received regulatory approval in both the United States and the European region for treating PE[28].

CDT, including UATh, may be combined with adjunctive mechanical procedures like aspiration or fragmentation to further expand clot surface area and potentiate fibrinolysis. Although generally safe, rare complications, including distal embolization, intraprocedural hemodynamic or respiratory instability, intracranial or major extracranial bleeding and pulmonary hemorrhage, have been reported in post-marketing surveillance databases.

Mechanical thrombectomy

Mechanical thrombectomy systems used for PE can be broadly categorized according to their mechanism of thrombus removal, including fragmentation devices, rheolytic systems and aspiration-based platforms. These devices aim to rapidly reduce thrombus burden and improve pulmonary blood flow while avoiding or minimizing the need for systemic thrombolytic therapy. These methods employ dedicated devices to physically debulk thromboembolic material and restore pulmonary blood flow, often in conjunction with adjunctive thrombolytic infusion, thereby reducing clot burden and improving hemodynamics.

Thrombus fragmentation and rotational thrombectomy: Mechanical disruption of pulmonary arterial thrombi using a pigtail catheter represents one of the earliest and least traumatic catheter-based techniques. Owing to its technical simplicity and low cost, this approach was historically widespread, although its use has declined with the introduction of more advanced technologies. In this technique, a modified pigtail catheter is manually rotated around a guidewire exiting through a side port. Thrombus disruption may be augmented by balloon maceration, typically using balloons smaller than the true vessel diameter, or by concurrent administration of thrombolytic agents. These strategies can be beneficial in hypotensive patients with central occlusions, as partial recanalization may rapidly restore forward flow and relieve RV strain as a bridge to further therapy. However, displacement of fragmented clot material into distal pulmonary branches may paradoxically exacerbate vascular obstruction and hemodynamic compromise[29]. To reduce the risk of distal embolization, newer over-the-wire rotational thrombectomy systems have been developed. These devices combine active mechanical fragmentation with a motor-driven, rotating flexible tip positioned within the thrombus, along with simultaneous aspiration to remove debris. Despite these advantages, rotational thrombectomy carries a risk of vascular injury to the pulmonary arterial wall. Moreover, existing studies are limited in size and robust data describing clinical efficacy remain sparse.

Rheolytic thrombectomy: Rheolytic thrombectomy, most commonly performed using the AngioJet system, relies on high-pressure saline jets to fragment thrombus while simultaneously aspirating debris through a vacuum mechanism. The device incorporates a dual-lumen catheter, with one lumen delivering pressurized saline and the other removing fluid and clot fragments, based on Bernoulli’s principle. Rheolytic thrombectomy has been applied across multiple clinical settings, including acute myocardial infarction during percutaneous coronary intervention and DVT treated with pharmacomechanical thrombolysis[30]. Reported adverse effects include transient hemolysis leading to reversible hemoglobinuria. Importantly, a meta-analysis evaluating invasive treatments for massive PE demonstrated a higher incidence of bradyarrhythmias, such as asystole and atrioventricular block, associated with rheolytic thrombectomy compared with other invasive approaches. These events are thought to be related to hemolysis-induced release of vasoactive substances, including adenosine, bradykinin and potassium, particularly after prolonged device activation[31]. Nonetheless, the ability to deliver thrombolytic agents locally may shorten procedure duration and accelerate restoration of pulmonary blood flow, potentially mitigating complication risk in selected cases[32].

Aspiration embolectomy: Aspiration embolectomy is designed to rapidly improve hemodynamics by physically removing thromboembolic material while minimizing distal clot migration. The concept was first introduced using a large-calibre catheter with manual suction applied at the hub. Contemporary aspiration techniques employ specialized large-bore catheters, typically 8 French or larger, to generate sufficient negative pressure for extraction of bulky or organized thrombi. Currently, three main aspiration systems have been most extensively evaluated in acute PE. The AngioVac system was among the earliest aspiration platforms and incorporates an extracorporeal veno-venous bypass circuit that filters aspirated blood before reinfusion via femoral and jugular access. More recently, this device has been evolved as a manually operated aspiration system with a deliverable cannula that does not require extracorporeal circulatory support. Its role in PE is currently being evaluated in ongoing clinical studies[33]. The FlowTriever system represents a dedicated large-lumen aspiration platform available in multiple catheter sizes. Access is obtained through the internal jugular or femoral vein, preferably under ultrasound guidance and catheter positioning in distal pulmonary branches requires a stiff guidewire with a flexible tip. The system includes large-bore aspiration catheters, a high-volume aspiration syringe and self-expanding nitinol mesh discs that can be deployed within the thrombus to facilitate retrieval when conventional aspiration is insufficient. An integrated blood filtration and reinfusion system allows return of aspirated hemoglobin serum to the individual. Thrombus removal can be achieved through direct aspiration, suction-assisted capture at the catheter tip, or disc-mediated extraction. Despite its versatility, the system’s size and rigidity may limit access to distal vessels and necessitate operator experience to optimize outcomes[34].

In contrast, the Indigo system offers a more flexible and lower-outline aspiration option, accompanied by catheters of smaller diameter that facilitate navigation into distal pulmonary branches. Continuous vacuum suction is combined with a separator wire designed to mechanically disrupt thrombus, while enhancing the aspiration efficiency. The catheter has the ability to be repeatedly forwarded via the clot to achieve incremental removal. An automated adjunct, the Lightning System, incorporates a microprocessor-driven algorithm to distinguish thrombus from blood and regulate suction, accordingly, thereby limiting blood loss, which typically remains modest and rarely necessitates transfusion[35]. Both FlowTriever and Indigo platforms may be combined with adjunctive local thrombolysis. The use of dedicated introducer sheaths with hemostatic valves is recommended to minimize access-site bleeding during aspiration procedures.

PRACTICAL CONSIDERATIONS AND EVIDENCE BASE

Timing, monitoring and imaging

Appropriate timing of percutaneous intervention is a key determinant of success. Patients at high risk require immediate treatment, whereas those at intermediate risk may tolerate brief delays. Evidence suggests that interventions performed within the first 24-48 hours of presentation are associated with superior safety and efficacy compared with later treatment. Current European Society of Cardiology recommendations advise initiation of reperfusion therapy within 60 minutes of diagnosis in high-risk cases, or within 90 minutes when transfer to a specialized center is required. Imaging during the procedure plays a critical role in defining thrombus location and overall embolic burden[36].

Selecting the optimal catheter-based reperfusion strategy

Choosing whether to pursue endovascular treatment along with selecting the most appropriate modality, requires careful balancing of anticipated benefits against procedural risks. Interpretation of available data is complicated by heterogeneity in patient populations, device types and reported outcomes. Nonetheless, existing evidence suggests that, in experienced hands, catheter-based therapies can achieve hemodynamic stabilization and in-hospital survival rates approaching 90%, although results vary according to clinical presentation and baseline comorbidities.

Reported complication rates vary among studies but are generally low in contemporary series. Major bleeding rates following CDT typically range from approximately 3%-10%, depending on thrombolytic dose and patient risk profile, while intracranial hemorrhage is rare and usually reported in less than 1% of cases. Mechanical thrombectomy devices have demonstrated similarly favorable safety profiles, with vascular access complications occurring in approximately 2%-5% of procedures and pulmonary artery injury or device-related complications reported only infrequently.

In clinical practice, management of these complications depends on their mechanism and severity. Bleeding complications are typically managed by cessation of thrombolytic infusion and adjustment or reversal of anticoagulation, while vascular access complications may require manual compression, imaging evaluation, or endovascular intervention when necessary. In cases of pulmonary artery injury or hemorrhage, supportive measures, temporary interruption of anticoagulation, airway protection and selective endovascular techniques such as balloon tamponade or coil embolization may be required. Severe hemodynamic deterioration during the procedure may necessitate vasopressor support or mechanical circulatory support, including extracorporeal membrane oxygenation in refractory cases.

Current evidence should be interpreted in light of the fact that much of the data supporting catheter-based therapies for PE derives from observational studies, prospective registries and single-arm device trials. While these studies consistently demonstrate improvements in RV function and pulmonary hemodynamics, their non-randomized design introduces potential limitations, including selection bias, heterogeneity in patient populations, variability in procedural techniques and differences in outcome definitions. As a result, direct comparisons with traditional treatments such as systemic thrombolysis or anticoagulation alone remain challenging. Although emerging RCTs are beginning to address these gaps, the current evidence base should be interpreted cautiously when extrapolating clinical efficacy and safety across broader patient populations. A summary of the expected complications of catheter-based therapies, including their mechanisms and practical management strategies, is provided in Table 2.

CDT is generally regarded as relatively safe, with bleeding, predominantly extracranial, being the most frequent complication and intracranial hemorrhage occurring infrequently. Mechanical thrombectomy, by contrast, may carry higher procedural risk due to the larger and less flexible catheters required, increasing the potential for pulmonary vascular injury[1].

Economic considerations are also increasingly relevant when evaluating reperfusion strategies for PE. Catheter-based interventions are generally associated with higher upfront procedural costs compared with systemic thrombolysis or anticoagulation alone, reflecting device expenses, catheter laboratory resources and specialized operator expertise. However, these procedures may potentially offset costs by reducing intensive care unit utilization, shortening hospitalization duration and lowering bleeding-related complications, particularly when thrombolytic exposure is minimized. Nevertheless, robust cost-effectiveness analyses comparing catheter-based interventions with conventional therapies remain limited and further health economic studies will be important to better define the overall value of these approaches in contemporary PE management.

Interdisciplinary collaboration

The expanding array of interventional devices and therapeutic strategies has increased the complexity of clinical decision-making in PE. In response, multidisciplinary models such as PERTs have been developed to facilitate rapid, collaborative assessment and treatment selection. These teams typically include emergency physicians, cardiologists, pulmonologists, interventional specialists and critical care clinicians, enabling real-time integration of diverse expertise. Growing evidence indicates that PERT implementation is associated with reductions in short-term and intermediate-term mortality and fewer hospital readmissions. Notably, the adoption of PERT models has coincided with increased use of interventional therapies in intermediate-risk PE populations[37].

SUPPORTING EVIDENCE

Evidence supporting catheter-based therapies for acute PE has expanded considerably over the past decade through RCTs, prospective registries and large observational studies evaluating CDT, UATh and mechanical thrombectomy. Early RCTs, including ULTIMA and OPTALYSE PE[27,28], demonstrated that CDT and UATh significantly improve RV function and pulmonary hemodynamics with relatively low bleeding risk compared with anticoagulation alone. Similarly, SEATTLE II and SUNSET-sPE confirmed the feasibility and safety of CDT[38,39], while emphasizing the importance of optimizing thrombolytic dose and infusion duration. Registry data, including KNOCOUT PE, further supported these findings by reporting low rates of major bleeding and intracranial hemorrhage alongside sustained improvements in RV performance[40,41]. Collectively, these studies established catheter-directed reperfusion as a promising alternative to systemic thrombolysis, particularly in patients at elevated bleeding risk or with contraindications to full-dose fibrinolysis.

The recently-published HI-PEITHO trial was the first large multinational RCT to evaluate UATh plus anticoagulation vs anticoagulation alone in patients with acute intermediate-risk PE characterized by RV dysfunction, elevated cardiac biomarkers and signs of cardiorespiratory distress[18]. A total of 544 patients were randomized to receive either low-dose alteplase delivered through the EkoSonic system or standard anticoagulation alone. The primary composite endpoint of PE-related death, cardiorespiratory decompensation or collapse, or recurrent PE within 7 days occurred significantly less frequently in the UATh group compared with the anticoagulation group [4.0% vs 10.3%; relative risk = 0.39, 95% confidence interval (CI): 0.20-0.77; P = 0.005], largely driven by a reduction in hemodynamic deterioration. Importantly, this clinical benefit was achieved without a significant increase in major bleeding and no intracranial hemorrhages were reported in either group. Additionally, patients treated with UATh demonstrated lower rates of rescue therapy and early improvement in RV function, supporting the role of catheter-directed fibrinolysis as an effective and relatively safe reperfusion strategy in selected patients with intermediate-risk PE.

More recently, growing evidence has supported aspiration-based mechanical thrombectomy as an effective reperfusion strategy capable of rapidly reducing thrombus burden while minimizing thrombolytic exposure. Trials such as FLARE and EXTRACT-PE demonstrated significant reductions in RV strain with favorable procedural safety profiles, findings that were reinforced by large real-world registries including FLASH[34,35,42]. The FLAME and PEERLESS trials further suggested potential clinical advantages of large-bore mechanical thrombectomy, including lower rates of clinical deterioration[43,44], reduced intensive care unit utilization and faster symptomatic recovery compared with CDT or conventional therapy, without excess major bleeding[45-48].

In our center, we organized a prospective single-center cohort of 25 consecutive patients with acute intermediate-high-risk PE treated with large-bore percutaneous mechanical thrombectomy using the FlowTriever system. We reported rapid and statistically significant improvements in multiple markers of PE severity, without major safety concerns. Key findings included an immediate reduction in systolic pulmonary artery pressure from 64 ± 10 mmHg to 38 ± 9 mmHg (P = 0.006), a reduction in heart rate from 111 ± 5 bpm to 89 ± 8 bpm post-procedure (P = 0.001) and a significant increase in cardiac index from 2.1 L/minute/m² to 3.1 L/minute/m² at 48 hours (P = 0.007). RV dysfunction also improved substantially, with a 17.5% reduction in RV/LV ratio at 48 hours (P < 0.001) and improved RV-pulmonary artery coupling (tricuspid annular plane systolic excursion/pulmonary artery systolic pressure). Importantly, there were no in-hospital deaths, no serious procedure-related complications and no deaths or recurrent PE/DVT events reported at 6-month follow-up, supporting the feasibility and favorable short-term safety profile of this approach in carefully selected intermediate-high-risk PE patients[49].

The recently published STORM-PE trial was the first international RCT to compare mechanical thrombectomy plus anticoagulation vs anticoagulation alone in patients with acute intermediate-high-risk PE[50]. In 100 randomized patients across 22 sites, mechanical thrombectomy produced a significantly greater reduction in RV/LV ratio at 48 hours (0.52 ± 0.37 vs 0.24 ± 0.40; between-group difference 0.27, 95%CI: 0.12-0.43; P < 0.001), alongside greater improvements in computed tomography-based pulmonary artery obstruction indices and earlier normalization of clinical parameters (including heart rate and oxygen requirements). Importantly, the composite major adverse event rate at 7 days was not significantly different between groups (4.3% vs 7.5%; P = 0.681), with similarly low major bleeding rates, although two PE-related deaths occurred in the thrombectomy arm. Overall, the trial demonstrated superior short-term improvement in RV dysfunction and thrombus burden with thrombectomy without an excess in major adverse events compared with anticoagulation alone[50].

Despite these encouraging results, most available studies remain limited by surrogate endpoints, relatively short follow-up durations and substantial heterogeneity in patient populations and procedural strategies. Consequently, the long-term impact of catheter-based reperfusion on survival, recurrent VTE and chronic complications such as chronic thromboembolic pulmonary hypertension remains incompletely defined, underscoring the need for larger RCTs with extended clinical follow-up (Table 3).

Table 3 Major clinical trials and registries evaluating catheter-based therapies for acute pulmonary embolism.

Trial	Therapy/device	Study design	Population	Main findings
ULTIMA	UATh (EkoSonic)	RCT	Intermediate-risk PE	Significant improvement in RV/LV ratio at 24 hours compared with anticoagulation alone, without increased major bleeding
SEATTLE II	UATh	Prospective single-arm study	Massive and submassive PE	Improved RV function and pulmonary pressures, but higher thrombolytic dose associated with increased bleeding
OPTALYSE PE	UATh	Randomized dose-optimization trial	Intermediate-risk PE	Lower-dose and shorter-duration thrombolysis improved RV function with favorable bleeding profile
SUNSET-sPE	UATh vs standard CDT	RCT	Intermediate-risk PE	Similar thrombus reduction between techniques with low major bleeding rates
CANARY	CDT vs anticoagulation	RCT	Intermediate–high-risk PE	Trial terminated early; interim data supported safety and feasibility of CDT
HI-PEITHO	UATh (EkoSonic) + anticoagulation vs anticoagulation alone	RCT	Intermediate-risk PE with RV dysfunction and cardiorespiratory distress	UATh significantly reduced the composite endpoint of PE-related death, hemodynamic decompensation/collapse or recurrent PE at 7 days (4.0% vs 10.3%) without increased major bleeding or intracranial hemorrhage
KNOCOUT PE	UATh	Prospective registry	Intermediate-high and high-risk PE	Low rates of major bleeding and intracranial hemorrhage with improved RV function
FLARE	FlowTriever thrombectomy	Prospective multicenter trial	Intermediate-risk PE	Significant reduction in RV/LV ratio with low major bleeding and minimal ICU utilization
FLASH	FlowTriever thrombectomy	Prospective registry	Real-world PE population	Confirmed safety and effectiveness with low adverse event rates
FLAME	FlowTriever vs contemporary therapies	Prospective comparative study	High-risk PE	Lower in-hospital adverse outcomes and mortality with thrombectomy
EXTRACT-PE	Indigo aspiration system	Prospective multicenter trial	Intermediate-risk PE	Significant reduction in RV strain with low major bleeding rates
PEERLESS	FlowTriever vs CDT	RCT	Intermediate-risk PE	Mechanical thrombectomy reduced clinical deterioration and ICU utilization without increasing bleeding
STORM-PE	Mechanical thrombectomy + anticoagulation vs anticoagulation	RCT	Intermediate–high-risk PE	Greater improvement in RV/LV ratio and thrombus burden without excess major adverse events

UATh: Ultrasound-assisted thrombolysis; CDT: Catheter-directed thrombolysis; RCT: Randomized controlled trial; PE: Pulmonary embolism; RV: Right ventricle; LV: Left ventricular; ICU: Intensive care unit.

ONGOING TRIALS AND FUTURE DIRECTIONS

Multiple ongoing clinical trials are actively investigating percutaneous strategies for acute PE, particularly in intermediate-high-risk patients. The PE-TRACT trial is designed to compare catheter-directed therapies or mechanical thrombectomy with standard anticoagulation in a large cohort of patients with PE[51]. Additional RCTs, including PRAGUE-26 and STRATIFY, are evaluating UATh against standard anticoagulation or low-dose systemic thrombolysis[52,53]. In parallel, several investigations are assessing next-generation aspiration thrombectomy platforms, including the APEX-AV trial evaluating the AlphaVac system in acute PE. Head-to-head comparisons between different catheter-based reperfusion strategies are also ongoing, most notably in the PEERLESS II trial, which aims to further define the relative benefits of large-bore mechanical thrombectomy compared with CDT and anticoagulation across intermediate- and intermediate-high-risk PE populations[54]. In addition, novel preventive approaches, including absorbable IVC filters designed to reduce long-term device-related complications, are currently under investigation. Collectively, these ongoing studies are expected to provide important insights into optimal patient selection and the future integration of percutaneous therapies into PE management algorithms, and are summarized in Table 4.

Table 4 Emerging catheter technologies and investigational systems in pulmonary embolism intervention.

Device/platform	Concep/device principle	Regulatory position (United States/European Union)	Trial/registry name	Identifier	Sample size (n)
AlphaVac F18 (AngioDynamics)	Mechanical thrombectomy based on aspiration (no extracorporeal circuit)	FDA cleared; CE marked	APEX-AV	NCT05318092	122
Helo PE (Endovascular Engineering)	Combined clot disruption + aspiration thrombectomy	Not approved (United States); not approved (European Union)	ENGULF	NCT05597891	25
WOLF (Boston Scientific)	Controlled thrombus extraction using finger-like retrieval elements	Approved for peripheral arteries; not approved specifically for PE (United States); not approved (European Union)	N/A	N/A	N/A
JET (Abbott)	High-pressure saline jet to fragment thrombus and facilitate aspiration	Approved for peripheral arteries; not approved for PE (United States); not approved (European Union)	N/A	N/A	N/A
Laguna (Innova Vascular)	Hybrid mechanical disruption plus aspiration	Approved for peripheral arteries; not approved for PE (United States); not approved (European Union)	TRUST	NCT06041594	107 (estimated)
Cleaner Pro (Argon Medical Devices)	Pharmacomechanical approach combining thrombectomy with local lytic infusion capability	Approved for peripheral arteries; not approved for PE ((United States); not approved (European Union)	CLEAN-PE	NCT06189313	125 (estimated)
Katana (Akura Medical)	Rheolytic-powered aspiration with directional control features	Not approved (United States); not approved (European Union)	QUADRA-PE	NCT06672510	118 (estimated)
Magneto eTrieve (Magneto Thrombectomy Solutions)	Large-bore aspiration combined with electromechanical clot extraction	Not approved (United States); not approved (European Union)	Safety and Performance of Magneto PE Kit	NCT04949048	10

FDA: Food and Drug Administration; CE: European conformity; PE: Pulmonary embolism; N/A: Not applicable.

CONCLUSION

Percutaneous catheter-based therapies for PE represent a rapidly advancing field with growing clinical relevance. Although current evidence suggests meaningful hemodynamic and clinical benefits in selected patients, high-quality randomized data remain limited and contemporary guidelines do not yet endorse these approaches as first-line therapy for any PE risk category. As device technology evolves, procedural safety improves and evidence continues to accumulate, a paradigm shift toward a “primary percutaneous pulmonary intervention” strategy may emerge, analogous to the evolution of care in ST-elevation myocardial infarction. Expanding percutaneous options have the potential to address the limitations of systemic thrombolysis, particularly by reducing bleeding-related morbidity and mortality. The development of regional PE networks and high-volume centers with multidisciplinary response teams may further optimize patient selection and outcomes. However, the long-term impact of these interventions on survival, recurrence of PE, and chronic complications such as CTEPH or post-PE syndrome remains insufficiently defined. Ultimately, the results of ongoing trials will be pivotal in defining the role of percutaneous therapies in the future management of PE. Future studies should aim to refine patient-selection criteria and treatment algorithms, particularly for intermediate-risk PE, where the optimal balance between systemic thrombolysis, catheter-based therapies and anticoagulation alone remains an area of active investigation.