Massive PE: thrombolysis versus surgical or catheter embolectomy

Most patients with PE are not hypotensive at presentation, and anticoagulation is the mainstay of treatment.^[3][7] This page is about the few who do: the patient in shock, the patient who arrests, and the stable patient who starts to slide. The choice is between a drug that dissolves clot, a catheter, a surgeon and, for the sickest, extracorporeal support.^[3][2] Diagnosis, risk scores and anticoagulant choice belong to the main PE page.

• Related topic: Pulmonary embolism: risk-stratified management.
• Related topic: Pulmonary hypertension: five groups and PAH-specific therapy.
• Related topic: Cardiogenic shock: staging, MCS selection and outcomes.

What massive PE means now

Massive PE is the older name.^[3] AHA/ACC 2026 recalls that a 2011 AHA scientific statement used three categories, low risk, submassive and massive PE, and that ESC 2019 then used four: low, intermediate-low, intermediate-high and high risk (Table 5 of the 2026 guideline).^[3] THANZ describes massive PE as haemodynamically unstable PE.^[7] AHA/ACC 2026 says that in surgical embolectomy cohort studies the vast majority of patients were traditionally classified as high-risk or massive PE, and it classifies them as Categories D1-E2 (30%-100%).^[3] The FLAME report says haemodynamically unstable high-risk, or massive, PE has a reported in-hospital mortality of over 25%.^[18]

ESC 2019: high risk means haemodynamic instability

ESC 2019 Table 4: definition of haemodynamic instability, which delineates acute high-risk PE (one of the following clinical manifestations at presentation)

^[1]

• ESC 2019 Table 8 footnote: haemodynamic instability, combined with PE confirmation on CTPA and/or evidence of RV dysfunction on TTE, is sufficient to classify a patient as high-risk PE; neither PESI nor troponin or other cardiac biomarkers is then necessary.^[1]
• Intermediate-high risk is the ESC 2019 Table 8 row without haemodynamic instability, with both RV dysfunction on TTE or CTPA and elevated cardiac troponin levels; its clinical-severity column (PESI class III–V or sPESI ≥I) is marked positive.^[2]
• Table 8 footnote e: RV dysfunction or elevated cardiac biomarkers may be present despite a PESI of I–II or an sPESI of 0, and until the implications are fully understood these patients should be classified as intermediate risk.^[1]

AHA/ACC 2026: Categories C to E

The 2026 AHA/ACC guideline presents a new classification, the Acute Pulmonary Embolism Clinical Categories, lettered A to E.^[3] Category C is symptomatic PE with an elevated clinical severity score; D is incipient cardiopulmonary failure; E is cardiopulmonary failure.^[3] The reperfusion rows are written for the subcategories below, so learn them as written.^[3]

AHA/ACC 2026 categories that carry reperfusion rows

^[3]

ESC 2019 rows name risk classes and AHA/ACC 2026 rows name lettered categories, so quote each row in the system it was written in.^[2][3] An ESC row for high-risk PE is not an AHA/ACC row for Category E1, even when the patient fits both.^[2][3]

^{[1] [2] [3]}

Why the right ventricle fails

ESC 2019 calls acute RV failure with low systemic output the leading cause of death in high-risk PE.^[1] AHA/ACC 2026 traces the chain.^[3] RV pressure-volume overload may cause RV dilation and decreased RV function, resulting in decreased LV filling and cardiac output.^[3] Compensatory increases in heart rate and systemic vascular resistance maintain systemic and myocardial perfusion.^[3]

That compensation is fragile.^[3] Anything that reduces or eliminates it, including most anxiolytic and analgesic drugs, can cause or worsen haemodynamic decompensation (AHA/ACC 2026).^[3] The same text says patients with acute PE and RV failure are often preload-dependent.^[3]

Reperfusion attacks the load itself.^[1][3] ESC 2019 says thrombolysis improves pulmonary obstruction, pulmonary artery pressure and pulmonary vascular resistance faster than UFH alone, with less RV dilation on echocardiography.^[1] AHA/ACC 2026 explains surgery the same way: on cardiopulmonary bypass, drainage of most of the venous return immediately reverses the RV pressure-volume overload.^[3] The RV can then recover, contracting in an unloaded state; VA-ECMO works in a comparable manner, with a similar effect on the RV.^[3]

^{[1] [3]}

Recognising the patient who needs reperfusion

In suspected high-risk PE the clinical probability is usually high.^[1] ESC 2019 says the differential diagnosis includes cardiac tamponade, acute coronary syndrome, aortic dissection, acute valvular dysfunction and hypovolaemia.^[1] Bedside TTE is the most useful initial test.^[1] In a highly unstable patient, echocardiographic evidence of RV dysfunction is sufficient to prompt immediate reperfusion without further testing (ESC 2019).^[1]

• ESC 2019 key message: in patients presenting with haemodynamic instability, perform bedside TTE as a fast, immediate step to differentiate suspected high-risk PE from other acute life-threatening situations.^[1]
• ESC 2019 text: for unstable patients taken directly to the catheterisation laboratory with suspected acute coronary syndrome, pulmonary angiography may be considered once ACS is excluded, if PE is a probable alternative and particularly if percutaneous catheter-directed treatment is an option.^[1]
• ESC 2019 text: acute PE is part of the differential diagnosis of cardiac arrest with a non-shockable rhythm against a background of pulseless electrical activity.^[1]
• AHA/ACC 2026 text: free-floating intracardiac clot-in-transit is found on echocardiography or CT in 2% to 4% of patients diagnosed with acute PE.^[3]

The normotensive patient who is not safe

Blood pressure can hide shock.^[3] AHA/ACC 2026 defines normotensive shock as isolated hypoperfusion without hypotension.^[3] Its listed markers include serum lactate >2 mmol/L, urine output <720 mL in 24 hours and cardiac index ≤2.2 L/min/m².^[3] The guideline adds that, in recent trials, the first 24 to 72 hours appear to be the critical time when haemodynamic collapse or laboratory changes are most commonly observed.^[3]

• AHA/ACC 2026: in Category D2, evaluating for the presence of normotensive shock can be useful to identify patients at increased risk for clinical deterioration and in-hospital death (COR 2a, LOE B-NR).^[3]
• AHA/ACC 2026: in Category C3, a MAP <80 mm Hg may be useful to identify patients who may require escalation of therapy (COR 2a, LOE B-NR).^[3]
• Its supporting text says observational data suggest patients with a MAP >80 mm Hg are at very low risk for in-hospital death or adverse outcomes.^[3]

Resuscitation: support the right ventricle while you decide

• ESC 2019: anticoagulation with UFH, including a weight-adjusted bolus injection, is recommended without delay in high-risk PE (Class I, Level C).^[2]
• ESC 2019 text: supplemental oxygen is indicated with PE and SaO2 <90%.^[1]
• AHA/ACC 2026: with moderate-severe hypoxia, heated high-flow nasal cannula (HFNC) oxygenation rather than standard nasal cannula can be beneficial to improve oxygenation (COR 2a, LOE C-LD).^[3]

Airway and sedation

Induction is a common moment of collapse.^[1][3] ESC 2019 says patients with RV failure are frequently hypotensive or highly susceptible to severe hypotension during induction of anaesthesia, intubation and positive-pressure ventilation.^[1] So it advises intubation only if the patient cannot tolerate or cope with non-invasive ventilation.^[1] Positive end-expiratory pressure should be applied with caution, because positive intrathoracic pressure may reduce venous return and worsen low cardiac output in high-risk PE.^[1]

• AHA/ACC 2026: in Categories C-E, deep sedation and mechanical ventilation should not be performed, unless clinically indicated, to avoid haemodynamic collapse (COR 3: Harm, LOE C-LD).^[3]
• AHA/ACC 2026: in Categories C-E needing sedation for intubation, vasopressors, inotropes and/or VA-ECMO should be available in case the patient becomes unstable (COR 1, LOE C-LD).^[3]
• AHA/ACC 2026 text: in one surgical embolectomy series, CPR was required after anaesthesia induction in 19% of patients who were all haemodynamically stable at induction; another series reported 28% (9/32).^[3]

Fluids, vasopressors and inotropes

ESC 2019 Table 9: treatment of RV failure in acute high-risk PE

^[1]

• ESC 2019: norepinephrine and/or dobutamine should be considered in high-risk PE (Class IIa, Level C).^[2]
• ESC 2019 text: if central venous pressure is low, a modest (≤500 mL) fluid challenge can be used, as it may increase the cardiac index, but volume loading has the potential to over-distend the RV and ultimately reduce systemic cardiac output.^[1]
• ESC 2019 text: norepinephrine can improve systemic haemodynamics without changing pulmonary vascular resistance, and its use should be limited to patients in cardiogenic shock.^[1]
• AHA/ACC 2026: for cardiogenic shock due to acute PE (Categories D2-E2), vasopressors and/or inotropes are recommended to improve cardiac output and systemic perfusion (COR 1, LOE C-LD).^[3]
• AHA/ACC 2026 text: norepinephrine is generally considered the vasopressor of choice; at doses ≤15 μg/min it has little to no effect on pulmonary vascular resistance, but above 15 μg/min it may raise it, so a second vasopressor (eg, vasopressin, phenylephrine) should be added rather than more norepinephrine.^[3]
• AHA/ACC 2026 text: dobutamine may be considered as an adjunct to norepinephrine with low cardiac output and hypotension (Category E1-2), and as the initial agent in normotensive cardiogenic shock (Category D2).^[3]
• AHA/ACC 2026: in Categories D1-2 with concern for reduced preload on clinical assessment, volume management with normal saline or other volume expanders may be considered to improve cardiac output and blood pressure (COR 2b, LOE C-LD); its text says small boluses (≤500 mL) may be considered in selected normotensive patients with signs of low cardiac output, and warns against larger volumes or indiscriminate fluid loading.^[3]
• AHA/ACC 2026: in Categories C2-E, inhaled pulmonary vasodilators may be considered to reduce RV afterload (COR 2b, LOE B-R).^[3]

Transfer

• AHA/ACC 2026: unstable patients (Category E) should not be transferred to another medical centre before their condition is stabilised (COR 3: Harm, LOE C-EO).^[3]
• Its text: unstable patients risk cardiovascular collapse, so immediate stabilisation before transfer is crucial, and potentially lifesaving interventions that are widely available, such as intravenous thrombolytic therapy, should not be delayed.^[3]
• AHA/ACC 2026: for haemodynamically stable patients with high-risk features (RV dysfunction and elevated cardiac biomarkers; Categories C3-D), transfer to a centre that can provide advanced therapies (examples: surgical embolectomy, CDL, MT, ECMO and IVC filter placement) may be considered to ensure access to appropriate interventions (COR 2b, LOE C-LD).^[3]
• The same text notes limited data on which patients benefit from transfer, and says patients unsuitable for transfer must be treated according to the best local expertise.^[3]

Systemic thrombolysis

For high-risk PE, ESC 2019 calls primary reperfusion the treatment of choice.^[1] In most cases that means systemic thrombolysis.^[1] Surgical embolectomy or catheter-directed treatment are the alternatives when thrombolysis is contraindicated, if expertise and resources are on-site.^[1]

Systemic thrombolysis rows (ESC 2019 and AHA/ACC 2026)

^{[2] [3]}

One AHA/ACC detail trips readers.^[3] Its Table 7 summary prints the systemic lysis cell for Categories A-C1 as 3-Harm A.^[3] The formal row for Categories A1-C2 gives COR 3: Harm, LOE B-R.^[3] Quote the formal row.

Regimens and doses as printed

ESC 2019 Table 10: thrombolytic regimens, doses and contraindications

^[1]

• ESC 2019 text: accelerated IV rtPA (100 mg over 2 h) is preferable to prolonged infusions of first-generation agents (streptokinase and urokinase).^[1]
• ESC 2019 text: UFH may be given during continuous infusion of alteplase, but should be discontinued during infusion of streptokinase or urokinase.^[1]
• ESC 2019 text: reteplase, desmoteplase and tenecteplase have also been investigated, but at the time none was approved for use in acute PE; reports on reduced-dose rtPA needed confirmation by solid evidence before any recommendation.^[1]
• AHA/ACC 2026 text: the FDA has approved streptokinase, urokinase and rt-PA (alteplase) for PE thrombolysis; tenecteplase, although not FDA approved for PE, has been tested in several clinical studies.^[3]
• AHA/ACC 2026 text: the first-generation agents are not used in contemporary practice because they need longer infusion times and are not readily available; standard-dose rt-PA (100 mg in 2 hours) is the most commonly used agent, with no head-to-head trials showing superiority of any agent.^[3]
• AHA/ACC 2026 text: evidence is emerging that lower-dose thrombolysis (25-50 mg rt-PA) may be as efficacious as standard dose (100 mg) with a reduced risk of major bleeding; a randomised trial of 118 patients with haemodynamic instability or massive PA obstruction reported similar efficacy and better safety with 50 mg than 100 mg.^[3]
• It concludes that low-dose regimens appear to have similar efficacy and lower bleeding risk, but more robust high-quality evidence is needed, and the ongoing PEITHO-3 trial of a reduced-dose alteplase regimen will add insight.^[3]

Timing, failure and bleeding

• ESC 2019 text: the greatest benefit is seen when treatment starts within 48 h of symptom onset, but thrombolysis can still be useful in patients with symptoms for 6–14 days.^[1]
• ESC 2019 text: unsuccessful thrombolysis, judged by persistent clinical instability and unchanged RV dysfunction on echocardiography after 36 h, has been reported in 8% of high-risk PE patients.^[1]
• ESC 2019 reports a meta-analysis of thrombolysis trials that included (but were not confined to) patients with high-risk PE, defined mainly as cardiogenic shock: a significant reduction in mortality and recurrent PE combined, with a 9.9% rate of severe bleeding and a 1.7% rate of intracranial haemorrhage.^[1]
• AHA/ACC 2026 text: four small RCTs with a total of 224 patients with high-risk PE reported improved pulmonary obstruction and less RV dilatation with systemic thrombolysis than with heparin alone; only one trial was confined to Categories E1-2, and it enrolled 8 patients before stopping.^[3]
• AHA/ACC 2026 text: overall, data suggest that patients with the highest PE mortality risk and lowest bleeding risk would obtain the greatest net benefit from thrombolysis, whereas those with the lowest mortality and highest bleeding risk would obtain the least benefit and are likely to be harmed.^[3]

Intermediate-high risk: anticoagulate, watch and plan

This is the haemodynamically stable patient with RV dysfunction on echocardiography or CTPA and an elevated troponin.^[1][2] ESC 2019 says that for most acute PE without haemodynamic compromise, anticoagulation without reperfusion is adequate treatment.^[1] Patients with RV dysfunction on echocardiography or CTPA and a positive troponin should be monitored over the first hours or days.^[1] The reason is the risk of early haemodynamic decompensation and circulatory collapse.^[1]

• ESC 2019 text: routine primary reperfusion, notably full-dose systemic thrombolysis, is not recommended, as the risk of potentially life-threatening bleeding appears too high for the expected benefit.^[1]
• ESC 2019 text: rescue thrombolysis or, alternatively, surgical embolectomy or percutaneous catheter-directed treatment should be reserved for patients who develop signs of haemodynamic instability.^[1]
• ESC 2019 text: in PEITHO the mean time between randomisation and death or haemodynamic decompensation was 1.79 ± 1.60 days in the placebo (heparin-only) arm, so it appears reasonable to keep patients with intermediate-high-risk PE on LMWH for the first 2-3 days and ensure they remain stable before switching to oral anticoagulation.^[1]
• AHA/ACC 2026 text: in PEITHO the mean time to haemodynamic collapse or escalation to lysis was 1.5 to 1.79 days ± 1.5 days, and close monitoring of Category C3 patients within the first 24 to 72 hours can be useful to identify those who may need escalation.^[3]
• AHA/ACC 2026 text: rescue thrombolysis was beneficial in PEITHO patients who collapsed after initial anticoagulation alone, and it is possible that a similar benefit could occur by giving rescue thrombolysis only to those who decompensate.^[3][10]
• AHA/ACC 2026 text: taken together, the role of systemic thrombolysis is less certain in Category C3.^[3]

^[2]

Catheter-directed therapy

Catheter therapy delivers either a drug or a device to the clot.^[3] AHA/ACC 2026 defines CDL as a thrombolytic, most commonly rt-PA, given through a multi-side-hole pulmonary catheter.^[3] The catheter may be standard or specialised, either ultrasound-assisted or with an expandable infusion basket.^[3] Mechanical thrombectomy (MT) extracts thrombus, commonly through the femoral vein.^[3]

• ESC 2019 text: catheters are used for mechanical fragmentation, thrombus aspiration, or more commonly a pharmacomechanical approach combining mechanical or ultrasound fragmentation with in situ reduced-dose thrombolysis.^[1]
• AHA/ACC 2026 text: MT devices span a variety of techniques, including large-, moderate- and small-bore suction thrombectomy, clot fragmentation, rheolysis, maceration, extirpation or a combined pharmacomechanical approach.^[3]
• AHA/ACC 2026 text: compared with other advanced therapies, MT devices need no concomitant lytic and no indwelling catheter or post-procedure ICU stay, and can sometimes remove older thrombus; MT has also been used as an adjunct in high-risk PE on mechanical circulatory support such as ECMO.^[3]

Catheter-directed therapy rows (ESC 2019 and AHA/ACC 2026)

^{[2] [3]}

• ESC 2019 footnote f: the risk-to-benefit ratios of surgical embolectomy or catheter-directed procedures have not yet been established in intermediate- or low-risk PE.^[2]
• AHA/ACC 2026 text: rt-PA doses in CDL studies ranged from 4 mg to 24 mg total over 2 to 24 hours; reduced dose means <5 mg per PA and standard dose 5 to 10 mg per PA; standard-dose regimens have been associated with more thrombus removal.^[3]
• AHA/ACC 2026 text: many factors influence the choice between CDL and MT, including operator experience, anatomic clot location, the perceived urgency and patient comorbidities.^[3]

How strong is the evidence?

• ESC 2019 text: most knowledge comes from registries and pooled case series, with procedural success (haemodynamic stabilisation, correction of hypoxia and survival to discharge) reaching 87%, although these results may be subject to publication bias.^[1]
• ESC 2019 reports one RCT of 59 patients with intermediate-risk PE in which ultrasound-assisted thrombolysis gave a larger decrease in the RV/LV diameter ratio at 24 h than heparin alone, without an increased risk of bleeding.^[1]
• ESC 2019 adds that, in one of two prospective cohorts, GUSTO severe and moderate bleeding was 10%, although intracranial haemorrhage was rare.^[1]
• ESC 2019 text: interpret these results with caution, given the small numbers, no studies directly comparing catheter-directed with systemic thrombolysis, and no RCT data on clinical efficacy outcomes.^[1]
• AHA/ACC 2026 text: more than 1000 patients treated with CDL have been studied prospectively, but fewer than 200 have been randomised against anticoagulants alone.^[3]
• AHA/ACC 2026 text: small RCTs show CDL relieves RV dysfunction faster than anticoagulants alone, measured by the RV/LV ratio, with low major bleeding; CDL may be an appropriate option in Categories D1-2.^[3]
• AHA/ACC 2026 text: CDL and systemic thrombolysis have not been compared directly; based on prospective single-arm studies, CDL may carry a lower risk of major and intracranial bleeding than systemic thrombolysis, but CDL plus anticoagulation likely carries more major bleeding than anticoagulation alone.^[3]
• AHA/ACC 2026 text: there are no randomised trials designed to compare MT with systemic thrombolysis in high-risk PE.^[3]
• AHA/ACC 2026 text: patients in Categories C2-3 who are stable on anticoagulation alone have a low risk of clinical deterioration, so a reperfusion strategy that carries risks is not indicated to prevent it.^[3]

Surgical embolectomy

Surgery opens the pulmonary arteries on cardiopulmonary bypass and removes the clot.^[1][3] ESC 2019 says it is usually carried out on cardiopulmonary bypass without aortic cross-clamping or cardioplegic arrest, then incision of both main pulmonary arteries with removal or suction of fresh clot.^[1] AHA/ACC 2026 describes it on bypass, typically through a sternotomy, with infrequent need for aortic cross-clamping.^[3]

Surgical embolectomy rows (ESC 2019 and AHA/ACC 2026)

^{[2] [3]}

• AHA/ACC 2026 text: there are no prospective randomised trials comparing surgical embolectomy with other treatments for acute PE; most data come from retrospective cohorts.^[3]
• AHA/ACC 2026 text: the surgical series are mostly Categories D2-E2 (30%-100%), including patients who had CPR (10%-40%) and salvage cases after failed thrombolysis (10%-30%); mortality ranged from 1% to 15% depending on preoperative confounders, and survival of >97% is reported in patients who did not need CPR.^[3]
• AHA/ACC 2026 text: fatal and nonfatal bleeding complications were higher with systemic thrombolysis than with surgical embolectomy, and there were no reports of ICH after surgical embolectomy but a notable risk with systemic thrombolysis.^[3]
• AHA/ACC 2026 text: Category E2 portends poor survival regardless of treatment; these patients account for most postoperative deaths, largely from anoxic brain injury after preoperative cardiac arrest, so the evidence is insufficient to favour surgery over other options such as VA-ECMO.^[3]
• ESC 2019 reports an observational retrospective New York State study of patients hospitalised with PE (1999-2013) in which first-line thrombolysis (n = 1854) and surgical embolectomy (n = 257) did not differ in 30-day mortality (15 and 13%), but thrombolysis was associated with a higher risk of stroke and re-intervention at 30 days and a higher rate of recurrent PE requiring readmission (7.9 vs 2.8%); the two treatments were not randomly allocated and the patients referred for surgery may have been selected.^[1]
• ESC 2019 reports a Society of Thoracic Surgeons database analysis of 214 patients having surgical embolectomy for high-risk (n = 38) or intermediate-risk (n = 176) PE, with in-hospital mortality of 12%, and 32% after pre-operative cardiac arrest.^[1]
• ESC 2019 text: recent reports indicate favourable surgical results in high-risk PE, with or without cardiac arrest, and in selected intermediate-risk PE.^[1]

ECMO and mechanical circulatory support

AHA/ACC 2026 says VA-ECMO provides end-organ perfusion while allowing for RV recovery or subsequent PE intervention.^[3] AHA/ACC 2026 says it rapidly decreases RV preload while delivering oxygenated blood to the tissues and end organs.^[3] ESC 2019 says no RCTs have tested ECMO in high-risk PE.^[1] It adds that ECMO carries a high incidence of complications, even when used briefly, and that stand-alone ECMO with anticoagulation is controversial.^[1]

• ESC 2019: ECMO may be considered, in combination with surgical embolectomy or catheter-directed treatment, in PE with refractory circulatory collapse or cardiac arrest, if appropriate expertise and resources are available on-site (Class IIb, Level C).^[2]
• AHA/ACC 2026: in acute, refractory cardiogenic shock from known or suspected PE (Category E2), it is reasonable to institute VA-ECMO, provided appropriate resources are available, to stabilise haemodynamics and improve oxygenation (COR 2a, LOE B-NR).^[3]
• AHA/ACC 2026: in Category E2 on VA-ECMO, the usefulness of additional advanced therapies is not well established (COR 2b, LOE C-LD).^[3]
• AHA/ACC 2026: on VA-ECMO, continuation of parenteral systemic anticoagulation is recommended in the absence of bleeding to prevent further thrombotic or embolic complications (COR 1, LOE B-NR); its text notes that bleeding is more frequent than thrombosis on VA-ECMO.^[3]
• ESC 2019 text: the bleeding risk of vascular access should be considered, particularly in patients undergoing thrombolysis.^[1]
• ESC 2019 text: recent experience appears to support combining ECMO with surgical embolectomy, particularly in high-risk PE with or without the need for CPR; it reports in-hospital and 1-year survival of 93 and 91% in one series of intermediate-risk PE (n = 28), high-risk PE without cardiac arrest (n = 18) and PE with cardiac arrest (n = 9).^[1]
• A 2022 systematic review and meta-analysis of 17 studies (327 patients with high-risk PE on ECMO) reported mortality of 22.6% with mechanical reperfusion (85.9% surgical embolectomy) and 42.8% with other strategies; its authors concluded that the results suggest mechanical reperfusion, notably surgical embolectomy, may yield favourable results.^[19]
• AHA/ACC 2026: in Categories D-E undergoing advanced interventions such as systemic thrombolysis, CDL, MT or surgical embolectomy, the benefit of IVC filter placement to reduce short-term recurrent PE and mortality is uncertain (COR 2b, LOE C-LD).^[3]
• For device selection in cardiogenic shock from other causes, see Cardiogenic shock: staging, MCS selection and outcomes.

Clot in transit

• AHA/ACC 2026: in Categories C3-E2 with free-floating right atrial and/or RV clot-in-transit, advanced therapies over anticoagulation alone are reasonable to reduce the risk of clinical deterioration (COR 2a, LOE C-LD).^[3]
• Its text cites a PERT Consortium Registry analysis linking clot-in-transit with mortality in 1442 Category E presentations (OR 2.26), and a pooled analysis of 316 patients with right heart thrombi reporting better survival with systemic thrombolysis than with anticoagulation alone.^[3]

Cardiac arrest from PE

Arrest is the extreme of high-risk PE.^[1][3] ESC 2019 says advanced life support guidelines should be followed when arrest is presumably caused by PE.^[1] The decision to treat PE must be taken early, while a good outcome is still possible.^[1] Thrombolytic therapy should be considered; once a thrombolytic is given, CPR should continue for at least 60–90 min before resuscitation attempts stop.^[1]

• ESC 2019 Table 10 footnote: the accelerated rtPA regimen (0.6 mg/kg over 15 min, maximum 50 mg) is not officially approved, but is sometimes used in extreme haemodynamic instability such as cardiac arrest.^[1]
• ANZCOR Guideline 11.10 (approved July 2026) suggests fibrinolytic drugs for cardiac arrest when PE is the suspected cause [CoSTR 2020, weak recommendation, very low-certainty evidence].^[5]
• It suggests fibrinolytic drugs or surgical embolectomy or percutaneous mechanical thrombectomy when PE is the known cause [CoSTR 2020, weak recommendation, very low certainty evidence].^[5]
• If a fibrinolytic is given in these circumstances, ANZCOR says consider CPR for 60 to 90 min before terminating resuscitation [Good Practice Statement].^[5]
• ANZCOR Guideline 11.5 (approved April 2025) suggests fibrinolytic drugs (e.g. alteplase 100mg) when PE is the suspected cause of cardiac arrest [CoSTR 2020, weak recommendation, very low certainty evidence].^[6]
• The same guideline recommends against routine administration of fibrinolytics for in- and out-of-hospital cardiac arrest [Good Practice Statement].^[6]
• ANZCOR 11.10 text: PE is considered present in 2% to 7% of out-of-hospital arrests, probably more in-hospital; ECPR may potentially facilitate fibrinolysis or embolectomy, but its role is unclear, and fibrinolysis given to patients without PE carries an increased bleeding risk.^[5]
• AHA/ACC 2026 places cardiac arrest without restoration of spontaneous circulation after 30 minutes of resuscitation in Category E2.^[3]

PE response teams

As soon as high-risk PE is diagnosed or strongly suspected, ESC 2019 asks you to select the best reperfusion option (systemic thrombolysis, surgical embolectomy or catheter-directed treatment) considering the patient’s risk profile and the resources and expertise available at your hospital.^[1] ESC 2019 says a PERT brings together specialists from different disciplines who convene in real time, face to face or by web conference.^[1] Its members include, for example, cardiology, pulmonology, haematology, vascular medicine, anaesthesiology or intensive care, cardiothoracic surgery and interventional radiology.^[1] The exact composition is not fixed and depends on each hospital’s resources and expertise.^[1]

• ESC 2019: set-up of a multidisciplinary team and a programme for the management of high- and (in selected cases) intermediate-risk PE should be considered, depending on the resources and expertise available in each hospital (Class IIa, Level C).^[2]
• AHA/ACC 2026: in patients at increased risk of adverse outcomes (Categories C-E), a multidisciplinary PERT assessment is recommended to improve in-hospital clinical care delivery (COR 1, LOE B-NR); its footnote adds that Categories A or B with multiple comorbidities may also benefit (eg, Category B with intracranial haemorrhage).^[3]
• AHA/ACC 2026 text: PERTs function similarly to code stroke or STEMI teams, and their membership and activation depend on each institution’s needs and resources.^[3]
• AHA/ACC 2026 text: studies show PERTs reduce time to therapeutic anticoagulation and IVC filter use, with shorter hospital and ICU stay in most studies; their effect on mortality is mixed and not yet conclusively established.^[3]

Choosing between thrombolysis, catheter and surgery

No randomised trial answers the head-to-head question in high-risk PE.^[3][1] The choice therefore rests on the guideline rows, bleeding risk and what your hospital can do now.^[1][3]

^{[2] [1] [3] [3]}

Special populations

Pregnancy and the post-partum period

Pregnancy appears in ESC 2019 Table 10 as a relative contraindication, together with the first post-partum week.^[1] Yet in pregnant or post-partum women with acute high-risk PE, a catheter-based reperfusion strategy or systemic thrombolysis should still be considered (ESC 2025, Class IIa, Level C).^[4] The 2025 ESC pregnancy guideline is newer than the 2019 ESC PE guideline for this group.^[4][2]

• ESC 2025 (pregnancy guideline, Recommendation Table 11): in pregnant or post-partum women with acute high-risk PE, a catheter-based reperfusion strategy or systemic thrombolysis should be considered (Class IIa, Level C).^[4]
• ESC 2025: in the same women, surgical thrombectomy may be considered as an alternative to a catheter-based approach or systemic thrombolysis (Class IIb, Level C).^[4]
• The ESC 2025 footnote defines high-risk PE as "according to the Pulmonary Embolism Severity Index from the 2019 ESC Guidelines".^[4]
• ESC 2025: with newly diagnosed VTE (DVT and/or PE) in pregnancy or the post-partum period, involvement of the Pregnancy Heart Team, including a vascular specialist and a haematologist, is recommended (Class I, Level C).^[4]
• ESC 2025 text: thrombolytic or interventional treatment is not recommended in the peripartum period and should only be considered in women with high-risk PE after consultation with a specialised multidisciplinary team.^[4]
• History: the ESC 2019 PE row said thrombolysis or surgical embolectomy should be considered for pregnant women with high-risk PE (Class IIa, Level C); ESC 2025 now says a catheter-based reperfusion strategy or systemic thrombolysis should be considered (Class IIa, Level C) and surgical thrombectomy may be considered as an alternative (Class IIb, Level C).^[2][4]
• ESC 2019 reports a systematic review of 127 severe PE cases (high- and intermediate-risk) in pregnancy and up to 6 weeks post-partum, 23% with cardiac arrest: survival was 94% after thrombolysis and 86% after surgical thrombectomy, possibly reflecting reporting bias; major bleeding after thrombolysis was 18% in pregnancy and 58% post-partum; fetal death was 12% after thrombolysis and 20% after thrombectomy.^[1]
• ESC 2019 text: thrombolytic treatment should not be used peri-partum except in life-threatening PE, and UFH is typically used in the acute treatment of high-risk PE.^[1]

After non-cardiac surgery

Recent surgery shapes this decision.^[1][20] ESC 2019 Table 10 lists major trauma, surgery or head injury in the previous 3 weeks as an absolute contraindication.^[1] The 2022 ESC non-cardiac surgery guideline is newer than the 2019 PE guideline for this group.^[20]

• ESC 2022 (non-cardiac surgery, Recommendation Table 34): in post-operative PE of high or intermediate clinical probability, initiation of anticoagulation is recommended without delay, while diagnostic work-up is in progress, if bleeding risk is low (Class I, Level C).^[20]
• ESC 2022 text (no class or level given): rescue thrombolytic therapy is recommended for PE with haemodynamic deterioration on anticoagulation in the post-operative phase, if possible, according to bleeding risk.^[20]
• ESC 2022 text (no class or level given): as an alternative to thrombolytic therapy for massive PE, surgical embolectomy or percutaneous catheter-directed treatment should be considered for haemodynamic deterioration on anticoagulation, particularly in patients with high bleeding risk.^[20]
• ESC 2022 text: the incidence of peri-operative VTE is unknown and likely underreported, and it is associated with high peri-operative mortality (∼17%).^[20]
• ESC 2022 (Recommendation Table 34): post-operative oral anticoagulation for PE is recommended for at least 3 months (Class I, Level C).^[20]

Older patients and bleeding risk

• In the 2014 Chatterjee meta-analysis of randomised trials (16 trials, 2115 patients), major bleeding with thrombolysis was not significantly increased in patients 65 years and younger (OR 1.25; 95% CI 0.50-3.14).^[12]
• AHA/ACC 2026 text: data suggest net benefit is greatest with the highest PE mortality and lowest bleeding risk, and least, with likely harm, at the lowest mortality and highest bleeding risk.^[3]

Complications and pitfalls

• Intracranial haemorrhage after thrombolysis: 1.7% in the meta-analysis ESC 2019 reports; in PEITHO, stroke occurred in 2.4% with tenecteplase (haemorrhagic in 10 of 12) and 0.2% with placebo.^[1][10]
• Thrombolysis can fail: 8% of high-risk patients had persistent instability and unchanged RV dysfunction after 36 h (ESC 2019 text).^[1]
• Sedation and intubation can precipitate collapse; AHA/ACC 2026 says deep sedation and mechanical ventilation should not be performed in Categories C-E, unless clinically indicated, to avoid haemodynamic collapse (COR 3: Harm, LOE C-LD).^[3]
• Fluid can hurt: ESC 2019 warns that volume loading can over-distend the RV and reduce cardiac output.^[1]
• Norepinephrine above 15 μg/min may raise pulmonary vascular resistance; AHA/ACC 2026 text says add a second vasopressor rather than increase the dose.^[3]
• ECMO complications rise with use beyond 5–10 days, including bleeding and infections (ESC 2019 Table 9).^[1]
• Do not under-dose CDL: AHA/ACC 2026 does not recommend a reduced dose of <5 mg alteplase per PA over a standard 5 to 10 mg per PA to reduce bleeding and/or fatal or nonfatal clinical deterioration (COR 3: No Benefit, LOE B-NR).^[3]
• Do not transfer the unstable patient (Category E) to another medical centre before stabilisation (AHA/ACC 2026, COR 3: Harm, LOE C-EO).^[3]

Prognosis and what happens next

• ESC 2019 text: after reperfusion and haemodynamic stabilisation, patients recovering from high-risk PE can be switched from parenteral to oral anticoagulation; they were excluded from the phase III NOAC trials, so the timing should be based on clinical judgement.^[1]
• ESC 2019 text: it remains unclear whether early thrombolysis for (intermediate- or high-risk) acute PE affects symptoms, functional limitation or CTEPH at long-term follow-up.^[1]
• ESC 2019 text: PEITHO findings do not support thrombolysis to prevent long-term sequelae after intermediate-risk PE, although clinical follow-up was available for only 62% of the study population.^[1]
• In the PEITHO long-term follow-up (median 37.8 months), mortality was 20.3% after tenecteplase and 18.0% after placebo (p = 0.43); CTEPH was confirmed in 2.1% and 3.2% (p = 0.79).^[11]
• For CTEPH and the pulmonary hypertension classification, see Pulmonary hypertension: five groups and PAH-specific therapy.

The trials behind the rows

AHA/ACC 2026 calls PEITHO the largest randomised trial of normotensive patients with acute PE and elements of increased risk for adverse events.^[3][10] Each card gives the trial population, design and result as its abstract reports them.

^{[10] [11] [13] [14] [15] [16] [17] [18]}

• The 2014 Chatterjee meta-analysis of 16 randomised trials (2115 patients) found thrombolysis associated with lower all-cause mortality (OR 0.53; NNT 59), more major bleeding (OR 2.73; NNH 18) and more ICH (OR 4.63; NNH 78).^[12]
• In its intermediate-risk trials, thrombolysis was associated with lower mortality (OR 0.48) and more major bleeding (OR 3.19); its authors add that findings may not apply to stable patients without RV dysfunction.^[12]
• AHA/ACC 2026 notes that Categories C2-D2 are being enrolled in several large outcome trials of CDL or MT against anticoagulation alone.^[3]

Evidence, guidelines and regional differences

The two main guidelines grade the same treatments with different systems.^[2][3] ESC uses class and level; AHA/ACC uses COR and LOE; ANZCOR says suggests or recommends.^[2][3][5]

Where ESC 2019 and AHA/ACC 2026 differ

^{[2] [3]}

In Australia and New Zealand

• THANZ (Med J Aust 2019 summary of its VTE guideline): thrombolysis or a suitable alternative is indicated for massive (haemodynamically unstable) PE.^[7]
• ANZCOR 2026 and 2025 cardiac arrest guidance on fibrinolysis, embolectomy and mechanical thrombectomy is given in the cardiac arrest section above.^[5][6]
• A 2026 Intern Med J local practice guideline (a consensus-based algorithm built after a retrospective audit at one hospital) states that there is no published guidance on a standard approach to when to use catheter-based therapy in the Australian setting.^[8]
• Its authors add that the absence of national consensus guidelines is a challenge as these therapies become more available.^[8]
• A 2026 Crit Care Resusc commentary on the 2026 AHA/ACC guideline in a regional ICU notes that most regional intensive care units in Australia cannot deliver catheter-directed and mechanical therapies on site.^[9]
• That commentary calls systemic thrombolysis the only on-site reperfusion option for a regional unit, and a reasonable choice for the deteriorating patient without prohibitive bleeding risk; its management table is a local adaptation, not prospectively validated.^[9]

Guidelines checked

A row called newer, or current, is so among the guidelines checked for this topic:

• Sources of the rows and statements used: ESC acute PE (2019, with the ERS; Eur Heart J text and Eur Respir J co-publication); AHA/ACC multisociety acute PE (2026, JACC co-publication); ESC cardiovascular disease and pregnancy (2025); ESC non-cardiac surgery (2022); ANZCOR Guidelines 11.10 (2026) and 11.5 (2025); THANZ VTE guideline summary (2019); and trial and review abstracts.^{[1][2][3][4][20][5][6][7][10]}
• No ESC acute PE guideline newer than 2019 was found in the census of PubMed and the guideline register, so the 2019 rows are quoted with their year and set beside the 2026 AHA/ACC rows.
• Not held as text, so not checked for this topic: the 2025 European Society for Vascular Medicine guideline on interventional treatment of VTE and the 2026 AHA/ACC perioperative guideline for noncardiac surgery.

Exam pearls

• High-risk PE (ESC 2019 Table 4) is cardiac arrest, obstructive shock or persistent hypotension at presentation; systemic thrombolytic therapy is recommended (Class I, Level B).^[1][2]
• High-risk PE with thrombolysis contraindicated or failed: ESC 2019 says surgical embolectomy is recommended (I, C) and catheter-directed treatment should be considered (IIa, C), each if expertise and resources are on-site.^[2]
• ESC 2019 Table 10: rtPA 100 mg over 2 h; accelerated 0.6 mg/kg over 15 min (maximum 50 mg), not officially approved, sometimes used in cardiac arrest.^[1]
• UFH may run during alteplase but is stopped during streptokinase or urokinase (ESC 2019).^[1]
• Ischaemic stroke within 6 months is an absolute contraindication; a TIA within 6 months is relative (ESC 2019 Table 10).^[1]
• After a thrombolytic in arrest, continue CPR for at least 60–90 min (ESC 2019 text); ANZCOR says consider 60 to 90 min.^[1][5]
• PEITHO (normotensive intermediate-risk PE with RV dysfunction and a positive troponin; tenecteplase plus heparin vs placebo plus heparin): death or haemodynamic decompensation within 7 days 2.6% vs 5.6%, at the cost of stroke (2.4% vs 0.2%) and extracranial bleeding (6.3% vs 1.2%).^[10]
• AHA/ACC 2026: during CDL, a reduced dose under 5 mg alteplase per PA is not recommended over a standard 5 to 10 mg per PA to reduce bleeding and/or fatal or nonfatal clinical deterioration (3: No Benefit, B-NR).^[3]
• AHA/ACC 2026: in Category E2 not on mechanical circulatory support, surgical embolectomy is not recommended over other advanced therapies for preventing short-term mortality (3: No Benefit, B-NR).^[3]

References20ShowHide

1. [1]Konstantinides SV, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J, 2020.PMID 31504429
2. [2]Konstantinides SV, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J, 2019.PMID 31473594
3. [3]Creager MA, et al. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2026.PMID 41712898
4. [4]De Backer J, et al. 2025 ESC Guidelines for the management of cardiovascular disease and pregnancy. Eur Heart J, 2025.PMID 40878294
5. [5]Australian and New Zealand Committee on Resuscitation Guideline 11.10 – Resuscitation in Special Circumstances ANZCOR, 2026.Source
6. [6]Australian and New Zealand Committee on Resuscitation Guideline 11.5 – Medications in Adult Cardiac Arrest ANZCOR, 2025.Source
7. [7]Tran HA, et al. New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism. Med J Aust, 2019.PMID 30739331
8. [8]Dunn A, et al. Multidisciplinary management of intermediate and high-risk pulmonary embolism in the era of mechanical thrombectomy: a local practice guideline. Intern Med J, 2026.PMID 41454751
9. [9]Maan P, et al. The 2026 pulmonary embolism guideline in a regional intensive care unit: Reading the recommendations without a catheter laboratory. Crit Care Resusc, 2026.PMID 42751124
10. [10]Meyer G, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med, 2014.PMID 24716681
11. [11]Konstantinides SV, et al. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol, 2017.PMID 28335835
12. [12]Chatterjee S, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA, 2014.PMID 24938564
13. [13]Kucher N, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation, 2014.PMID 24226805
14. [14]Sadeghipour P, et al. Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-risk Pulmonary Embolism: The CANARY Randomized Clinical Trial. JAMA Cardiol, 2022.PMID 36260302
15. [15]Rosenfield K, et al. Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism. N Engl J Med, 2026.PMID 41910345
16. [16]Jaber WA, et al. Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial. Circulation, 2025.PMID 39470698
17. [17]Lookstein RA, et al. Randomized Controlled Trial of Mechanical Thrombectomy With Anticoagulation Versus Anticoagulation Alone for Acute Intermediate-High Risk Pulmonary Embolism: Primary Outcomes From the STORM-PE Trial. Circulation, 2026.PMID 41183181
18. [18]Silver MJ, et al. Outcomes in High-Risk Pulmonary Embolism Patients Undergoing FlowTriever Mechanical Thrombectomy or Other Contemporary Therapies: Results From the FLAME Study. Circ Cardiovasc Interv, 2023.PMID 37847768
19. [19]Chopard R, et al. Optimal reperfusion strategy in acute high-risk pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis. Eur Respir J, 2022.PMID 35487534
20. [20]Halvorsen S, et al. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J, 2022.PMID 36017553