2019 ESC/ERS Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism

Authors, Journal, Affiliations, Type, DOI

• Authors: Konstantinides SV* (Chairperson), Meyer G* (Co-Chairperson), Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jiménez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ní Ainle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL
• Journal: European Heart Journal (2020) 41, 543–603; online publish-ahead-of-print 31 August 2019
• Affiliations: ESC Task Force for the diagnosis and management of acute pulmonary embolism, developed in collaboration with the European Respiratory Society (ERS). Participating ESC entities: ACCA, ACNAP, EACVI, EACPR, HFA, and the Working Groups on Aorta and Peripheral Vascular Diseases, Cardiovascular Surgery, Pulmonary Circulation and Right Ventricular Function, and Thrombosis
• Type: De novo ESC clinical practice guideline — fourth in the series, following 2000, 2008 and 2014. Systematic evidence review with ESC Class of Recommendation (I/IIa/IIb/III) and Level of Evidence (A/B/C) grading. 61 pages; 17 sections including the guidelines' own "Key messages", "Gaps in the evidence" and "'What to do' and 'what not to do'" summaries
• DOI: 10.1093/eurheartj/ehz405

Overview

This is the fourth ESC guideline on acute pulmonary embolism and the document that established the four-tier risk classification (high / intermediate-high / intermediate-low / low) which has organised PE management, trial enrolment and the catheter-directed-lysis debate ever since. Risk category is defined by haemodynamic instability at the top, then by clinical severity scores (PESI/sPESI), right ventricular dysfunction and cardiac biomarkers — an integration rather than a single parameter. Its therapeutic backbone is anticoagulation started immediately on suspicion, systemic thrombolysis as Class I for high-risk PE but explicitly Class III for routine use in intermediate- or low-risk PE (reserved for rescue after haemodynamic deterioration), NOACs preferred over the LMWH–VKA sequence, and a minimum of 3 months of anticoagulation with indefinite extension determined by the recurrence risk of the index event's risk factor. It also formalises the post-PE follow-up pathway — routine review at 3–6 months, then investigation for chronic thromboembolic disease or CTEPH in anyone with persistent dyspnoea — and separates CTED (chronic thromboembolic disease, no PH at rest) from CTEPH. The 2026 AHA/ACC multi-society guideline supersedes this risk scheme with the A–E categories, but this document remains the source of the ESC definitions that most published PE trials still enrol against.

Keywords

Guidelines · pulmonary embolism · venous thrombosis · shock · dyspnoea · heart failure · right ventricle · diagnosis · risk assessment · echocardiography · biomarkers · treatment · anticoagulation · thrombolysis · pregnancy · venous thromboembolism · embolectomy

Key Takeaways

Recommendation Grading (Tables 1–2)

• Class I — "is recommended or is indicated"; Class IIa — "should be considered"; Class IIb — "may be considered"; Class III — "is not recommended" (in some cases may be harmful)
• Level A — multiple RCTs or meta-analyses; Level B — a single RCT or large non-randomised studies; Level C — expert consensus and/or small studies, retrospective studies, registries

2. Introduction — What Changed Since 2014

2.2.1 New or Revised Concepts in 2019

• D-dimer cut-offs adjusted for age or clinical probability offered as an alternative to the fixed cut-off
• A clear word of caution that RV dysfunction may be present, and affect early outcomes, in patients classed as "low risk" by clinical scores
• Thoroughly revised haemodynamic and respiratory support section for high-risk PE
• The risk-adjusted management algorithm was revised to weigh clinical severity, aggravating conditions/comorbidity, and RV dysfunction together
• Reduced-dose apixaban or rivaroxaban for extended anticoagulation should be considered after the first 6 months
• Cancer: edoxaban or rivaroxaban should be considered as an alternative to LMWH, with a caution for gastrointestinal cancer because of increased bleeding risk
• Pregnancy: a dedicated diagnostic algorithm was proposed, plus updated radiation-absorption data
• Long-term sequelae: an integrated model of post-PE care was proposed, and recommendations extended to the entire spectrum of post-PE symptoms and functional limitation, not only CTEPH

2.2.2 Recommendations Changed from 2014 to 2019

2.2.3 Other New Recommendations in 2019

• Age-adjusted or clinical-probability-adapted D-dimer cut-off as an alternative to the fixed cut-off (IIa)
• If a positive proximal CUS is used to confirm PE, risk assessment should be considered to guide management (IIa)
• V/Q SPECT may be considered for PE diagnosis (IIb)
• Assessment of the RV by imaging or biomarkers should be considered even when PESI is low or sPESI is 0 (IIa)
• Validated scores combining clinical, imaging and laboratory prognostic factors may be considered to further stratify severity (IIb)
• A NOAC is the recommended form of oral anticoagulation in eligible patients (I)
• Multidisciplinary teams for high-risk and selected intermediate-risk PE (IIa)
• ECMO may be considered in combination with surgical embolectomy or catheter-directed treatment in refractory circulatory collapse or cardiac arrest (IIb)
• Indefinite VKA for antiphospholipid antibody syndrome (I)
• Extended anticoagulation for: no identifiable risk factor (IIa); a persistent risk factor other than APS (IIa); a minor transient/reversible risk factor (IIa)
• Reduced-dose apixaban or rivaroxaban after the first 6 months (IIa)
• Amniotic fluid embolism should be considered in unexplained haemodynamic instability or respiratory deterioration with DIC in a pregnant or post-partum woman (IIa)
• Thrombolysis or surgical embolectomy should be considered for pregnant women with high-risk PE (IIa); NOACs are not recommended in pregnancy or lactation (III)
• Routine clinical evaluation 3–6 months after acute PE (I); integrated model of care after acute PE (I)
• Referral of symptomatic patients with mismatched perfusion defects on V/Q beyond 3 months to a PH/CTEPH expert centre (I)

3. General Considerations

3.1 Epidemiology

• VTE, clinically presenting as DVT or PE, is the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke
• Annual PE incidence 39–115 per 100,000 population; DVT 53–? per 100,000
• Incidence is almost eight times higher in people aged >80 than in the fifth decade; annual PE incidence rates are rising over time
• PE may cause <300,000 deaths per year in the US; in six European countries with a combined population of 454.4 million, more than 370,000 deaths were related to VTE in 2004
• Case fatality rates appear to be falling while incidence rises, over an ~15-year period — attributed to more effective therapies and better guideline adherence
• In children, VTE incidence is 53–57 per 100,000 among hospitalised patients and 1.4–4.9 per 100,000 in the community

4. Diagnosis

Diagnostic Strategy (Section 7.1, Figures 4–5)

• With haemodynamic instability: bedside transthoracic echocardiography is the immediate first step to differentiate high-risk PE from other causes of shock (tamponade, ACS, aortic dissection, acute valvular dysfunction, hypovolaemia); if RV dysfunction is present and CTPA is immediately available and feasible, proceed to CTPA. RV/LV diameter ratio >1.0 is the main echocardiographic criterion in this emergency setting
• Without haemodynamic instability: assess clinical probability first, then D-dimer in low/intermediate probability or PE-unlikely patients, then CTPA as second-line when D-dimer is elevated and first-line when clinical probability is high
• Bedside venous ultrasound combined with cardiac ultrasound increases specificity in unstable patients; a normal echocardiogram plus normal venous ultrasound had a 96% negative predictive value for PE in one study

D-dimer

• Plasma D-dimer, preferably by highly sensitive assay, is recommended in outpatients/ED patients with low or intermediate clinical probability, or who are PE-unlikely, to reduce unnecessary imaging and irradiation (I/A)
• Age-adjusted cut-off (age × 10 μg/L in patients aged >50) should be considered as an alternative (IIa/B)
• Clinical-probability-adapted cut-off (the YEARS model) should be considered as an alternative (IIa/B) — PE excluded at D-dimer <1000 μg/L with no YEARS items, or <500 μg/L with ≥1 item
• D-dimer is not recommended in high clinical probability — a normal result does not safely exclude PE even with a highly sensitive assay (III/A)
• D-dimer testing in pregnancy/post-partum was upgraded from IIb (2014) to IIa

CTPA and Other Imaging

• Reject PE without further testing if CTPA is normal in low/intermediate clinical probability or PE-unlikely patients (I/A); accept PE without further testing if CTPA shows a segmental or more proximal filling defect with intermediate or high clinical probability (I/B)
• With high clinical probability or PE-likely, rejecting PE on a normal CTPA should be considered (IIa/B)
• Further imaging for isolated subsegmental filling defects may be considered (IIb/C)
• CT venography as an adjunct to CTPA is not recommended (III/B); MRA is not recommended to rule out PE (III/A)
• Normal perfusion lung scan excludes PE without further testing (I/A); a high-probability V/Q scan should be considered diagnostic (IIa/B); a non-diagnostic V/Q scan combined with negative proximal CUS excludes PE in low-probability patients (IIa/B)
• V/Q SPECT may be considered for PE diagnosis (IIb/B) — a low grade reflecting the limitations catalogued in the guideline's Table 5
• Echocardiography is not a diagnostic test for PE; it is used for risk stratification and, in the unstable patient, to identify RV dysfunction rapidly

Lower-limb Compression Ultrasonography

• A proximal DVT on CUS in a patient with clinical suspicion of PE confirms VTE and PE (I/A)
• Distal DVT only → further testing should be considered (IIa/B); if a positive proximal CUS is used to confirm PE, severity assessment should be considered so management can be risk-adjusted (IIa/C)

5. Assessment of Severity and Risk of Early Death

Table 8 — ESC 2019 Four-Tier Classification

Clinical Parameters and Scores (Table 7)

• PESI (original): age, male sex (+10), cancer (+30), chronic heart failure (+10), chronic pulmonary disease (+10), pulse ≥110 (+20), SBP <100 (+30), respiratory rate >30 (+20), temperature <36 °C (+20), altered mental status (+60), O₂ saturation <90% (+20). Classes: I ≤65 points (very low, 0–1.6% 30-day mortality), II 66–85 (low, 1.7–3.5%), III 86–105 (moderate, 3.2–7.1%), IV 106–125 (high, 4.0–11.4%), V >125 (very high, 10.0–24.5%)
• sPESI (simplified): 1 point each for age >80, cancer, chronic cardiopulmonary disease, pulse ≥110, SBP <100, O₂ saturation <90%. 0 points = 30-day mortality 1.0% (95% CI 0.0–2.1%); ≥1 point = 10.9%
• Concomitant DVT is independently associated with death within 3 months of acute PE

Right Ventricular Imaging

• RV dysfunction is found on echocardiography in ≥25% of unselected acute PE patients; it is associated with increased early mortality. An RV/LV diameter ratio >1.0 is the key echocardiographic threshold
• Echocardiography also identifies right-to-left shunt through a patent foramen ovale and right heart thrombi, both associated with increased mortality; PFO additionally increases ischaemic stroke risk from paradoxical embolism in patients with RV dysfunction
• The guideline's explicit caution: RV dysfunction may be present and affect early outcomes in patients who look "low risk" by clinical score — hence the IIa recommendation to assess RV and biomarkers even with low PESI or sPESI 0. A meta-analysis of 21 cohorts (3,295 "low-risk" patients by PESI I–II or sPESI 0) found 34% (95% CI 30–39%) had signs of RV dysfunction

Biomarkers

• Cardiac troponins (I or T) have low specificity and positive predictive value in normotensive patients on their own, but are informative in combination. High-sensitivity troponin T <14 pg/mL had a 98% negative predictive value for excluding adverse in-hospital outcome in a prospective multicentre cohort of 526 normotensive patients
• BNP/NT-proBNP reflect RV stretch from pressure overload; likewise low specificity alone but useful when low (negative predictive value) in combination with other findings
• H-FABP (heart-type fatty acid-binding protein), an early marker of myocardial injury, provides prognostic information in unselected and normotensive patients
• Lactate ≥2 mmol/L predicts PE-related complications, reflecting imbalance between tissue oxygen supply and demand — a marker of overt or imminent haemodynamic compromise
• Elevated creatinine / reduced GFR relate to 30-day all-cause mortality; hyponatraemia predicted in-hospital mortality (OR 5.6, 95% CI 3.4–9.1) in a meta-analysis of 18,616 patients; copeptin (vasopressin surrogate) has shown utility in derivation and validation cohorts

5.6 Prognostic Assessment Strategy

• Risk assessment begins at suspicion of PE and continues through the diagnostic workup; classification of severity and early (in-hospital or 30-day) death risk is summarised in the guideline's Table 8
• The intermediate group is subdivided by whether both RV dysfunction and elevated troponin are present (intermediate-high) or one or none is positive (intermediate-low)
• Validated combined scores incorporating clinical, imaging and laboratory parameters may be considered as an alternative approach to further stratify severity (IIb)

6. Treatment in the Acute Phase

Initial Anticoagulation (6.2, 6.7)

• Initiation of anticoagulation is recommended without delay in patients with high or intermediate clinical probability while the diagnostic workup is in progress (I/C)
• LMWH or fondaparinux is recommended over UFH for most patients when parenteral anticoagulation is started in the absence of haemodynamic instability (I/A)
• In suspected high-risk PE, i.v. UFH with a weight-adjusted bolus should be initiated without delay (I/C)
• When oral anticoagulation is started in a patient eligible for a NOAC (apixaban, dabigatran, edoxaban, rivaroxaban), a NOAC is recommended in preference to a VKA (I/A)
• With a VKA, overlapping parenteral anticoagulation until INR 2.5 (range 2.0–3.0) is recommended (I/A)
• NOACs are not recommended in severe renal impairment, during pregnancy and lactation, or in antiphospholipid antibody syndrome (III/C). Dabigatran is not recommended at CrCl <30 mL/min; edoxaban 30 mg once daily at CrCl 15–50 and not recommended <15; rivaroxaban and apixaban used with caution at CrCl 15–29 and not recommended <15

Reperfusion Treatment (6.3, 6.6, 6.7)

• Systemic thrombolysis is recommended for high-risk PE (I/B). Thrombolysis produces faster improvement in pulmonary obstruction, PAP and PVR than UFH alone, with reduced RV dilation
• Rescue thrombolytic therapy is recommended for patients with haemodynamic deterioration on anticoagulation (I/B) — an upgrade from IIa in 2014
• Routine use of primary systemic thrombolysis is not recommended in intermediate- or low-risk PE (III/B)
• Percutaneous catheter-directed treatment should be considered for high-risk PE in whom thrombolysis is contraindicated or has failed (IIa/C); as an alternative to rescue thrombolysis in haemodynamic deterioration it should also be considered (IIa/C), if appropriate expertise and resources are on site
• Surgical pulmonary embolectomy is recommended for high-risk PE in whom thrombolysis is contraindicated or has failed (I/C), performed with cardiopulmonary bypass without aortic cross-clamping or cardioplegic arrest
• The guideline notes the risk-to-benefit ratios of surgical embolectomy and catheter-directed procedures have not yet been established in intermediate- or low-risk PE — the evidence gap later addressed by HI-PEITHO and PRAGUE-26
• Most knowledge of catheter-based embolectomy derives from registries and pooled case series, with procedural success rates defined as haemodynamic stabilisation
• Norepinephrine and/or dobutamine should be considered in high-risk PE (IIa/C)
• ECMO may be considered, in combination with surgical embolectomy or catheter-directed treatment, in refractory circulatory collapse or cardiac arrest (IIb). Its place in high-risk PE awaits prospective cohort evidence
• Post-operative ECMO is recommended as standard of care in PEA centres; combining ECMO with surgical embolectomy is supported by recent experience, particularly in high-risk PE with or without CPR

Thrombolytic Regimens (Table 10)

• Absolute contraindications to fibrinolysis: prior haemorrhagic stroke or stroke of unknown origin; ischaemic stroke within 6 months; CNS neoplasm; major trauma, surgery or head injury within 3 weeks; bleeding diathesis; active bleeding
• Relative: transient ischaemic attack within 6 months, oral anticoagulation, pregnancy or first post-partum week, non-compressible puncture sites, traumatic resuscitation, refractory hypertension (systolic BP >180 mmHg), advanced liver disease, infective endocarditis, active peptic ulcer

Multidisciplinary PE Teams (6.4, 6.8)

• Set-up of a multidisciplinary team and programme for high-risk and (in selected cases) intermediate-risk PE should be considered, depending on local resources and expertise (IIa/C). The concept originated in the USA as rapid-response teams for "severe" PE

Inferior Vena Cava Filters (6.5, 6.9)

• IVC filters should be considered with absolute contraindications to anticoagulation (IIa/C), and in PE recurrence despite therapeutic anticoagulation (IIa/C)
• Routine use of IVC filters is not recommended (III/A) — no mortality benefit, with increased DVT risk (PREPIC, PREPIC2)
• Reported complications include filter fracture and/or embolisation, DVT extending to the vena cava, and difficulties with retrieval of permanent filters

Early Discharge and Home Treatment (6.10, 7.2.3)

• Carefully selected low-risk patients should be considered for early discharge and continuation of treatment at home, if proper outpatient care and anticoagulant treatment can be provided (IIa/A)
• Three criteria must be satisfied: low risk of early PE-related death or serious complications; absence of serious comorbidity; and a practical/social setup permitting home treatment
• Both the Hestia exclusion criteria (a bedside checklist) and PESI/sPESI are capable of identifying low-risk patients free of serious comorbidity — using either is acceptable
• In prospective cohort studies of patients treated at home with or without short hospitalisation, 3-month rates of thromboembolic recurrence, major bleeding and death were 1.75%, 1.43% and 2.83%
• An open question flagged by the guideline: whether excluding intermediate-risk PE on clinical grounds alone is adequate, or whether RV dysfunction and myocardial injury assessment is needed before home treatment

7. Integrated Risk-Adapted Diagnosis and Management

• Figure 6 (Central Illustration) sets out the risk-adjusted management strategy integrating clinical PE severity, aggravating conditions/comorbidity, and RV dysfunction
• For most PE without haemodynamic compromise, parenteral or oral anticoagulation without reperfusion is adequate; normotensive patients with at least one indicator of elevated risk need closer monitoring
• High-risk PE: immediate anticoagulation, then the best reperfusion option chosen by risk profile and local resources/expertise
• Intermediate-high risk: reperfusion is not first-line, but the guideline advises prospectively planning the management strategy with the team so a contingency plan is ready if the situation deteriorates
• Low risk: triage to early discharge and home treatment
• Patients recovering from high-risk PE can be switched from parenteral to oral anticoagulation after reperfusion and haemodynamic stabilisation, but because these patients were excluded from the phase III NOAC trials, the optimal timing of that transition is not established by evidence

8. Chronic Treatment and Prevention of Recurrence

Table 11 — Risk of Long-Term Recurrence by Index-Event Risk Factor

• The guideline avoids the terms "unprovoked" and "idiopathic" in favour of describing the index event's risk factor
• Anticoagulants are highly effective during treatment but do not eliminate recurrence risk after discontinuation
• Thrombophilia testing (antiphospholipid antibodies and lupus anticoagulant) may be considered in patients with VTE at a young age (e.g. <50 years) and without an otherwise identifiable risk factor
• Estimated annual major bleeding risk on VKAs was ~3% in older cohorts; in extended-treatment phase III trials, major bleeding may reach ~1% and clinically relevant non-major bleeding as high as 6%

8.4 Recommendations — Regimen and Duration (No Cancer)

• Therapeutic anticoagulation for ≥3 months is recommended for all patients with PE (I/A)
• Major transient/reversible risk factor → discontinuation after 3 months is recommended (I/B)
• Recurrent VTE (≥1 previous PE or DVT) not related to a major transient/reversible risk factor → oral anticoagulation of indefinite duration is recommended (I)
• Antiphospholipid antibody syndrome → indefinite VKA is recommended (I/B)
• First PE, no identifiable risk factor → indefinite extended oral anticoagulation should be considered (IIa/A)
• First PE, persistent risk factor other than APS → extended, IIa/C; first PE, minor transient/reversible risk factor → extended, IIa/C
• Reduced-dose NOAC: if extended anticoagulation is decided in a patient without cancer, apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily should be considered after 6 months of therapeutic anticoagulation (IIa)
• Patients who refuse or cannot tolerate any oral anticoagulant: aspirin or sulodexide may be considered for extended prophylaxis (IIb/B). Aspirin showed a 30–35% relative reduction in recurrence vs placebo in two trials (1,224 patients); sulodexide reduced recurrence by ~50% in 615 patients with a first unprovoked VTE
• In patients on extended anticoagulation, drug tolerance and adherence, hepatic and renal function, and bleeding risk should be reassessed at regular intervals (I/C)

8.5–8.6 PE in Patients with Cancer

• Patients with cancer, particularly gastrointestinal cancer, should be encouraged to continue LMWH for ≥3–6 months
• Weight-adjusted subcutaneous LMWH should be considered for the first 6 months over VKAs (IIa/A)
• Edoxaban (IIa/B) or rivaroxaban (IIa/C) should be considered as an alternative to LMWH in patients without gastrointestinal cancer — the caution reflects increased bleeding risk in GI tumours
• Choice between LMWH and a NOAC is otherwise left to physician discretion, especially in those with anticipated low bleeding risk
• Extended anticoagulation beyond 6 months should be considered indefinitely, or until the cancer is cured (IIa/B)
• Incidental PE in cancer should be managed in the same manner as symptomatic PE if it involves segmental or more proximal branches, multiple subsegmental vessels, or a single subsegmental vessel with detected DVT (IIa/C)
• After the first 3–6 months, extended treatment may be continuation of LMWH or transition to an oral anticoagulant; two cohort studies assessed LMWH safety to ≤12 months
• Because a proportion of patients with apparently unprovoked PE develop cancer within the first year, the guideline addresses occult malignancy screening in this context

9. Pulmonary Embolism and Pregnancy

9.5 Recommendations

• Formal diagnostic assessment with validated methods is recommended if PE is suspected in pregnancy or post-partum (I/B)
• D-dimer measurement and clinical prediction rules should be considered to rule out PE in pregnancy or the post-partum period (IIa/B) — upgraded from IIb in 2014
• Venous CUS should be considered in a pregnant patient with suspected PE, particularly with DVT symptoms, to avoid unnecessary irradiation (IIa/B)
• Perfusion scintigraphy or CTPA (low-radiation-dose protocol) should be considered to rule out PE; CTPA is first-line if the chest X-ray is abnormal (IIa/C)
• A therapeutic fixed dose of LMWH based on early-pregnancy body weight is the recommended therapy for most pregnant women without haemodynamic instability (I/B)
• Thrombolysis or surgical embolectomy should be considered for pregnant women with high-risk PE (IIa/C)
• NOACs are not recommended during pregnancy or lactation (III/C)
• Spinal or epidural needle insertion is not recommended unless ≥24 h have elapsed since the last therapeutic LMWH dose (III/C)
• LMWH is not recommended within 4 h of epidural catheter removal (III/C)
• Amniotic fluid embolism should be considered in a pregnant or post-partum woman with otherwise unexplained cardiac arrest, sustained hypotension or respiratory deterioration, especially with disseminated intravascular coagulation (IIa/C). Management rests on high-quality emergency care, prompt treatment of bleeding and coagulopathy, and awareness of AFE in emergency algorithms

10. Long-Term Sequelae of Pulmonary Embolism

10.1 Functional Limitation and Deconditioning

• Pulmonary arterial patency is restored in most survivors within a few months, so no routine follow-up CTPA is needed in such patients
• Persisting or deteriorating dyspnoea and poor physical performance are frequently present 6 months to 3 years after acute PE
• Muscle deconditioning — particularly with excess body weight and cardiopulmonary comorbidity — is largely responsible for reported functional limitation, rather than residual thrombi or persistent PH
• Whether early reperfusion (notably thrombolysis) affects long-term symptoms, functional limitation or persistent PH remains unclear

10.2 Chronic Thromboembolic Pulmonary Hypertension

• CTEPH is caused by persistent obstruction of pulmonary arteries by organised thrombi, leading to flow redistribution and secondary remodelling of the pulmonary microvascular bed. Its hallmark is fibrotic transformation of a pulmonary arterial thrombus causing fixed mechanical obstruction
• Risk factors/predisposing conditions (Table 13) — related to the acute event: previous PE/DVT, large pulmonary arterial thrombi on CTPA, echocardiographic signs of PH/RV dysfunction, CTPA findings suggesting pre-existing chronic thromboembolic disease. Concomitant conditions: ventriculo-atrial shunts, infected chronic i.v. lines or pacemakers, splenectomy, thrombophilic disorders (particularly APS and high factor VIII), non-O blood group, hypothyroidism treated with thyroid hormones, history of cancer, myeloproliferative disorders, inflammatory bowel disease, chronic osteomyelitis
• A history of acute PE was reported by 75% of patients in an international CTEPH registry. Before surgical treatment became available, mean PAP >30 mmHg was related to poor survival
• Diagnosis is based on findings after at least 3 months of effective anticoagulation, requiring mean PAP ≥25 mmHg with characteristic organised thrombi (see Contradictions — the 2022 ESC/ERS PH guideline has since lowered this threshold)
• Planar V/Q lung scan is the suitable first-line imaging modality — 96–97% sensitivity and 90–95% specificity for CTEPH. SPECT appears less sensitive than planar V/Q when assessed at a level. CTPA should not be used as a stand-alone test to exclude CTEPH
• Surgical pulmonary endarterectomy (PEA) is the treatment of choice for operable CTEPH — a true bilateral endarterectomy through the medial layer, requiring deep hypothermia and intermittent circulatory arrest. Post-operative ECMO is standard of care in PEA centres; reperfusion oedema may require veno-arterial ECMO and severe persistent PH may need bridging to lung transplantation
• Balloon pulmonary angioplasty (BPA) is effective for technically inoperable CTEPH, dilating obstructions down to subsegmental vessels. The largest registry (249 patients, mean age 61.5, seven Japanese centres, 2004–2013) showed mean PAP falling from 43 to 24 mmHg
• Pharmacological treatment: optimal medical therapy consists of anticoagulants plus diuretics and oxygen for heart failure or hypoxaemia. Lifelong oral anticoagulation with VKAs is recommended, including after successful PEA or BPA. The effect of PAH-approved drugs on clinical worsening in CTEPH has not been clarified by RCTs, and no data exist for technically operable patients with prohibitive comorbidity
• Medical therapy is not indicated in symptomatic survivors of acute PE with post-thrombotic obstructions but no PH at right heart catheterisation at rest — this is the CTED entity, distinguished from CTEPH

10.3–10.4 Follow-Up Strategy and Recommendations

• A proposed follow-up strategy (Figure 8) checks at 3–6 months for dyspnoea and/or functional limitation, VTE recurrence, cancer, and bleeding complications of anticoagulation. Dyspnoea severity can be standardised with the Medical Research Council scale or WHO functional class
• If symptoms persist, TTE is the next step to assess the probability of chronic PH; if mismatched perfusion defects are found on V/Q, referral to a PH/CTEPH expert centre is indicated
• If the V/Q scan is normal and symptoms remain unexplained, alternative causes including deconditioning and comorbidity are pursued
• Asymptomatic patients with CTEPH risk factors (Table 13) may be scheduled for further follow-up visits
• Recommendations: routine clinical evaluation 3–6 months after acute PE (I/B); an integrated model of post-PE care involving hospital specialists, qualified nurses and primary care physicians (I); referral of symptomatic patients with mismatched perfusion defects persisting on V/Q beyond 3 months to a PH/CTEPH expert centre, taking into account echocardiography, natriuretic peptide levels and/or CPET (I/C); further diagnostic evaluation should be considered for persistent or new-onset dyspnoea/exercise limitation (IIa/C); and may be considered in asymptomatic patients with CTEPH risk factors (IIb/C — upgraded from III in 2014)

12. Key Messages (the Guideline's Own 10)

1. In haemodynamic instability, bedside TTE is the immediate first step to differentiate suspected high-risk PE from other acute life-threatening situations
2. If acute PE is suspected, institute anticoagulation as soon as possible while the workup is ongoing, unless the patient is bleeding or has absolute contraindications
3. Use validated diagnostic algorithms including standardised pre-test probability and D-dimer testing — they avoid unnecessary, expensive and potentially harmful imaging and ionising radiation exposure
4. If CTPA suggests single subsegmental PE, consider a false-positive finding — discuss with the radiologist and/or seek a second opinion to avoid misdiagnosis and unnecessary, potentially harmful anticoagulation
5. Confirmation of PE without haemodynamic instability must be followed by further risk assessment — clinical findings, RV size/function, and laboratory biomarkers — to decide on reperfusion, monitoring, or early discharge with ambulatory anticoagulation
6. On diagnosing high-risk PE, select the best reperfusion option (systemic thrombolysis, surgical embolectomy, or catheter-directed treatment) by risk profile and available resources/expertise. For intermediate-high-risk PE, reperfusion is not first-line, but plan the management strategy prospectively with a contingency plan ready
7. Prefer a NOAC over the LMWH–VKA regimen unless contraindicated
8. Except for PE provoked by a strong transient/reversible risk factor, there is a lifelong risk of VTE recurrence after a first PE — re-examine at 3–6 months, weigh benefits against risks, decide on extension and dose, and recommend regular follow-up, e.g. yearly
9. If PE is suspected in pregnancy, use diagnostic pathways including CTPA or V/Q lung scan, which can be used safely during pregnancy
10. Patients should not be lost to follow-up after acute PE. Check for VTE recurrence, cancer and bleeding complications, and ask about persisting or new-onset dyspnoea or functional limitation — if present, implement a staged workup to exclude CTEPH or chronic thromboembolic disease and to detect/treat comorbidity or simple deconditioning. Follow-up imaging is not routinely recommended in asymptomatic patients, but may be considered with CTEPH risk factors

13. Gaps in the Evidence (the Guideline's Own)

• Diagnosis — the optimal method to adjust the D-dimer threshold by age or clinical probability; the diagnostic value and significance of isolated subsegmental filling defects in the modern CTPA era; whether to anticoagulate incidental PE versus watchful waiting; and the benefits versus risks of "triple rule-out" CT angiography in non-traumatic chest pain
• Severity assessment — the optimal combination and cut-off levels of clinical and biochemical predictors of early PE-related death; and whether RV assessment in addition to clinical parameters is needed to classify a patient as low versus intermediate risk
• Acute treatment — the clinical benefits versus risks of reduced-dose thrombolysis and catheter-based reperfusion modalities in intermediate-high-risk PE should be evaluated in prospective randomized trials (this is the gap HI-PEITHO and PRAGUE-26 subsequently addressed); the place of ECMO in high-risk PE awaits prospective evidence; the optimal anticoagulant and regimen at CrCl <30 mL/min remains unclear; and the criteria for selecting patients for early discharge — particularly whether RV imaging and/or biomarkers are needed
• Chronic treatment — the clinical value of recurrence and bleeding risk scores; confirmation of reduced-dose extended treatment in patients at high recurrence risk; extended evidence for NOACs in cancer; the regimen and dose after the first 6 months in cancer; and the optimal time to discontinue anticoagulation in cancer
• Pregnancy — diagnostic algorithms using modern radiological imaging with low radiation doses need prospective testing in adequately powered cohorts; controversy persists over the optimal LMWH dose and regimen in pregnancy; and any foetal effects of inadvertent NOAC exposure should be recorded
• Long-term sequelae — the optimal follow-up strategy and spectrum of diagnostic tests for persisting symptoms and functional limitation; and the criteria for identifying asymptomatic patients whose CTEPH risk justifies further investigation

14. 'What to Do' and 'What Not to Do' — Selected Messages

• Do: bedside echocardiography or emergency CTPA in suspected high-risk PE (I); i.v. UFH with weight-adjusted bolus without delay in suspected high-risk PE (I); validated diagnostic criteria in suspected PE without instability (I); anticoagulation while the workup is in progress if clinical probability is high or intermediate (I); highly sensitive plasma D-dimer in low/intermediate probability or PE-unlikely patients (I); reject PE if CTPA is normal at low/intermediate probability (I); reject PE if the perfusion scan is normal (I); accept PE if CTPA shows a segmental or more proximal filling defect at intermediate/high probability (I); accept VTE if CUS shows proximal DVT with clinical suspicion of PE (I)
• Do: stratify by haemodynamic instability (I), then further stratify intermediate versus low risk (I); systemic thrombolysis for high-risk PE (I); surgical embolectomy where thrombolysis is contraindicated or has failed (I); prefer LMWH or fondaparinux over UFH parenterally in the absence of instability (I); prefer a NOAC when eligible (I); VKA overlapped with parenteral anticoagulation to INR 2.5 (range 2.0–3.0) as an alternative (I); rescue thrombolysis for haemodynamic deterioration on anticoagulation (I); therapeutic anticoagulation for ≥3 months in all patients (I); discontinue after 3 months for a first PE from a major transient/reversible factor (I); continue indefinitely for recurrent VTE unrelated to a major transient/reversible factor (I); continue VKA indefinitely in APS (I); reassess tolerance, adherence, hepatic/renal function and bleeding risk at regular intervals on extended treatment (I); formal diagnostic assessment if PE is suspected in pregnancy/post-partum (I); therapeutic fixed-dose LMWH based on early-pregnancy weight in most pregnant women without instability (I); routinely re-evaluate patients 3–6 months after acute PE (I); implement an integrated model of post-PE care (I); refer symptomatic patients with mismatched perfusion defects on V/Q beyond 3 months to a PH/CTEPH expert centre (I)
• Do not: do not measure D-dimer in high clinical probability — a normal result does not safely exclude PE (III); do not perform CT venography as an adjunct to CTPA (III); do not perform MRA to rule out PE (III); do not routinely administer systemic thrombolysis as primary treatment in intermediate- or low-risk PE (III); do not routinely use IVC filters (III); do not use NOACs in severe renal impairment or in antiphospholipid antibody syndrome (III); do not use NOACs during pregnancy or lactation (III); do not insert a spinal or epidural needle within 24 h of the last LMWH dose (III); do not administer LMWH within 4 h of epidural catheter removal (III)

Limitations of the document

• Superseded on risk classification. The four-tier scheme (high / intermediate-high / intermediate-low / low) has been replaced in the 2026 AHA/ACC multi-society guideline by the A–E Acute PE Clinical Categories. This source remains the reference definition for most published trial populations, but it is no longer current guidance on classification
• Superseded on the CTEPH haemodynamic threshold. Diagnosis here requires mean PAP ≥25 mmHg; the 2022 ESC/ERS pulmonary hypertension guideline lowered the threshold to >20 mmHg (see concepts/Pulmonary-Hypertension). The two documents are internally inconsistent within the same society's output
• Terminology drift. This guideline uses CTED (chronic thromboembolic disease) for post-thrombotic obstruction without PH at rest; the 2026 AHA/ACC guideline uses CTEPD. The entities are equivalent but the acronyms differ
• Evidence base for advanced therapies is weak. Catheter-directed treatment rests on registries and pooled case series; the guideline states explicitly that the risk-to-benefit ratio of surgical embolectomy and catheter-directed procedures has not been established in intermediate- or low-risk PE, and it flags the absence of prospective randomized evaluation of catheter-based reperfusion as an evidence gap
• The intermediate-risk reperfusion question is unresolved within this document. Routine primary systemic thrombolysis is Class III, yet rescue thrombolysis is Class I — a strategy of "watch and rescue" that the guideline itself does not validate against prophylactic treatment
• High-risk PE patients were excluded from the phase III NOAC trials, so the timing of transition from parenteral to oral anticoagulation in that group is not evidence-based
• Publication date. Evidence review concluded 2019 (online August 2019). It predates PEITHO-3, PEERLESS, HI-PEITHO, PRAGUE-26, and the 2022 ESC/ERS PH guideline
• Conflict of interest and sponsorship. Standard ESC disclosure process; corresponding author affiliated with the Center for Thrombosis and Hemostasis, Mainz. No independent funding statement is given in the document itself

Key Concepts Mentioned

• concepts/Acute-PE-Clinical-Categories — this guideline's four-tier scheme is the scheme the AHA/ACC A–E categories replaced; the mapping between them is the central translational problem in acute PE
• concepts/Venous-Thromboembolism-Anticoagulation — source for the recurrence-risk categorisation (Table 11) that structures duration decisions, and for the NOAC-over-VKA recommendation
• concepts/Pulmonary-Hypertension — the 2022 ESC/ERS guideline that supersedes this document's mPAP threshold for CTEPH
• concepts/Cancer-Associated-VTE — LMWH first-line for the first 6 months; NOAC alternatives only outside gastrointestinal cancer
• concepts/Balloon-Pulmonary-Angioplasty — BPA for technically inoperable CTEPH; largest registry (249 patients) mean PAP 43 → 24 mmHg
• CTED (chronic thromboembolic disease) — post-thrombotic obstruction without PH at rest; medical therapy not indicated. Renamed CTEPD in the 2026 AHA/ACC guideline
• PESI and sPESI — the clinical severity scores at the centre of the four-tier scheme
• YEARS model — clinical-probability-adapted D-dimer thresholds (1000/500 μg/L)
• Hestia criteria — bedside checklist identifying low-risk patients suitable for home treatment
• Amniotic fluid embolism — considered in unexplained cardiac arrest, sustained hypotension or respiratory deterioration with DIC in pregnancy or post-partum
• Sulodexide — alternative extended prophylaxis where oral anticoagulation is refused or not tolerated

Key Entities Mentioned

• entities/Pulmonary-Embolism — primary entity
• entities/CTEPH — the guideline's follow-up pathway, risk factors (Table 13), and PEA-first treatment hierarchy
• European Society of Cardiology (ESC) / European Respiratory Society (ERS) — issuing bodies
• The Task Force for the diagnosis and management of acute pulmonary embolism — Konstantinides (Chair), Meyer (Co-Chair)

Wiki Pages Updated

• Created: wiki/sources/acute-pe-esc-2019.md
• Updated: wiki/sourceindex.md
• Updated: wiki/wikiindex.md
• Updated: wiki/entities/Pulmonary-Embolism.md
• Updated: wiki/concepts/Acute-PE-Clinical-Categories.md
• Updated: wiki/entities/CTEPH.md
• Updated: wiki/concepts/Venous-Thromboembolism-Anticoagulation.md