Definition and pathophysiology
Acute pulmonary embolism (PE) is classified according to haemodynamic status, clinical severity, evidence of right-ventricular (RV) dysfunction, and myocardial injury. This classification is central to determining the intensity of monitoring, supportive treatment, anticoagulation, and possible reperfusion.
The principal pathophysiological determinant of early adverse outcome is acute RV failure. In acute PE, obstruction of pulmonary blood flow increases RV pressure load and may impair RV filling and forward output. The resulting syndrome may progress to systemic congestion, reduced cardiac output, haemodynamic collapse, and death. The clinical consequences are particularly important when pulmonary vascular obstruction is accompanied by limited cardiopulmonary reserve or other adverse comorbidity.
The classification of acute PE comprises four clinically useful groups:
High-risk PE, also termed massive PE, is defined by haemodynamic instability and represents approximately 5–10% of cases.
Intermediate-high-risk PE occurs in haemodynamically stable patients with both RV dysfunction on imaging and elevated cardiac biomarkers.
Intermediate-low-risk PE includes stable patients who are not low risk but have either RV dysfunction or elevated biomarkers, or neither of these abnormalities in the presence of abnormal clinical risk assessment.
Low-risk PE is characterized by clinical low-risk features, negative cardiac biomarkers, and no imaging evidence of RV dysfunction.
Catastrophic or “supermassive” PE refers to refractory cardiogenic shock or the need for ongoing cardiopulmonary resuscitation. Mechanical circulatory support, including extracorporeal membrane oxygenation (ECMO), may be required in this setting.
Clinical presentation and symptoms
The clinical presentation reflects the severity of RV pressure overload and the extent of circulatory compromise. Features associated with an unfavourable short-term prognosis include:
Tachycardia
Low systolic blood pressure
Respiratory insufficiency, manifested by tachypnoea and/or low arterial oxygen saturation
Syncope
These findings may occur singly or in combination. Syncope is particularly important as a marker of potentially severe disease. The presence of haemodynamic instability places the patient in the high-risk category and requires urgent evaluation for reperfusion treatment.
Evaluation and physical examination
Initial assessment
Risk stratification begins with an immediate search for haemodynamic instability. This determines whether the patient has high-risk PE and therefore requires an emergency management pathway.
Patients without haemodynamic instability require more detailed prognostic evaluation using two complementary domains:
Indicators of acute PE severity, including clinical findings, RV dysfunction on imaging, and myocardial injury shown by laboratory testing.
Comorbidity and aggravating conditions, which may worsen early prognosis even when haemodynamic status is initially preserved.
Physical examination should therefore focus on:
Blood pressure and evidence of hypotension
Heart rate and tachycardia
Respiratory rate and oxygenation
Evidence of systemic congestion or acute RV failure
Syncope or altered clinical status
Comorbid cardiopulmonary disease, active cancer, and other conditions incorporated into validated clinical risk tools
Acute RV failure is a rapidly progressive syndrome characterized by systemic congestion resulting from impaired RV filling and/or reduced RV output. Recognition of this syndrome is critical because it may precede haemodynamic collapse.
Clinical risk scores
Validated clinical tools, including the Pulmonary Embolism Severity Index (PESI), its simplified form, and the Hestia criteria, are used to assess clinical risk. These instruments incorporate haemodynamic and respiratory variables such as tachycardia and hypoxaemia, together with age and comorbidities including active cancer and cardiopulmonary disease.
Clinical scoring should not replace assessment of RV function and myocardial injury. In haemodynamically stable patients, the combination of clinical risk assessment, imaging, and biomarkers provides the basis for distinguishing low-risk PE from intermediate-low- and intermediate-high-risk disease.
Risk stratification
High-risk PE
High-risk PE is defined primarily by haemodynamic instability. Systolic hypotension is most often defined as systolic blood pressure below 90 mmHg. High-risk patients generally have abnormal RV findings on imaging, elevated troponin, or both, although the haemodynamic definition takes precedence.
This category includes patients with shock or cardiac arrest. Patients with refractory cardiogenic shock or requiring ongoing cardiopulmonary resuscitation may be described as having catastrophic or supermassive PE.
Intermediate-risk PE
Intermediate-risk PE occurs in patients who are haemodynamically stable but do not meet low-risk criteria. It is divided into two groups.
| Risk group | Haemodynamic status | Clinical risk | RV dysfunction on imaging | Cardiac biomarkers |
|---|---|---|---|---|
| Intermediate-high | Stable | Increased | Present | Elevated |
| Intermediate-low | Stable | Increased or not low risk | Present or absent | Elevated or normal |
Intermediate-high-risk PE is defined by the combination of RV dysfunction and elevated cardiac biomarkers. Intermediate-low-risk PE is diagnosed when only one of these abnormalities is present, or when neither is present but clinical assessment remains abnormal.
Low-risk PE
Low-risk PE is characterized by:
Haemodynamic stability
Low-risk clinical assessment by PESI, simplified PESI, or Hestia criteria
Negative cardiac biomarkers
No imaging evidence of RV dysfunction
A subset of patients with low-risk PE may be suitable for home treatment if reliable follow-up is available.
Limitations of risk stratification
The optimal combination of clinical and biochemical predictors of early PE-related death, including appropriate cut-off levels, remains uncertain. This is particularly relevant when identifying patients with intermediate-risk PE who might benefit from reperfusion. The additional value of systematic RV assessment beyond clinical parameters for separating low- from intermediate-risk PE also requires further prospective confirmation.
Diagnostics
Electrocardiography
The source material does not provide specific electrocardiographic criteria or characteristic ECG findings for acute PE.
Imaging
Imaging is used principally to identify RV dysfunction and pressure overload after PE has been diagnosed or is strongly suspected. Echocardiographic or computed tomographic evidence of RV dysfunction contributes directly to risk classification.
In stable patients:
RV dysfunction plus elevated cardiac biomarkers indicates intermediate-high risk.
RV dysfunction without biomarker elevation indicates intermediate-low risk.
Absence of RV dysfunction and negative biomarkers supports low-risk classification when clinical risk is also low.
Echocardiography provides a non-invasive assessment of RV pressure overload and function. The source material identifies transthoracic echocardiography as an important component of prognostic evaluation but does not specify individual echocardiographic measurements or cut-off values.
Computed tomography may also demonstrate RV dysfunction. The source material does not provide specific CT thresholds or quantitative criteria.
Diagnostic approach in haemodynamic instability
In patients presenting with haemodynamic instability, the diagnostic and therapeutic process is emergent. Once high-risk PE is suspected and the clinical setting supports the diagnosis, anticoagulation should be initiated without delay and primary reperfusion is generally the treatment of choice.
Diagnostic approach without haemodynamic instability
Patients without haemodynamic instability undergo advanced risk stratification. This combines:
Clinical risk assessment
Imaging evaluation of RV function
Measurement of cardiac biomarkers
Evaluation of comorbidities and aggravating conditions
The results guide the choice between anticoagulation alone, closer monitoring with rescue reperfusion if deterioration occurs, and outpatient or home-based management in selected low-risk patients.
Biomarkers and laboratory findings
Cardiac troponins are used to identify myocardial injury associated with acute RV strain. Their interpretation is integrated with imaging and clinical risk.
Elevated troponin with RV dysfunction: intermediate-high-risk PE in a haemodynamically stable patient.
Elevated troponin without RV dysfunction: intermediate-low-risk PE.
Negative cardiac biomarkers without RV dysfunction, together with low clinical risk: low-risk PE.
The source material does not specify particular troponin assays, natriuretic peptide thresholds, renal or hepatic laboratory criteria, or other laboratory markers.
Treatment and management
Management is risk-adjusted and has three principal objectives:
Immediate stabilization of circulation and organ perfusion.
Anticoagulation to prevent further thrombus propagation and embolization.
Reperfusion in patients whose clinical risk warrants rapid reduction of pulmonary vascular obstruction.
The level of care depends on haemodynamic status, the severity of RV dysfunction, biomarker findings, clinical risk, comorbidity, and the availability of appropriate expertise and resources.
Acute treatment of high-risk PE
Anticoagulation
Unfractionated heparin (UFH), including a weight-adjusted bolus injection, should be started without delay in patients with high-risk PE.
After reperfusion and haemodynamic stabilization, parenteral anticoagulation can be changed to oral therapy. Patients with high-risk PE were excluded from the phase III trials of non-vitamin K antagonist oral anticoagulants, so the precise timing of transition is not established by those data and must be individualized.
When oral therapy is selected, tested regimen requirements must be respected:
Apixaban requires a higher initial dose during the first 1 week after PE diagnosis.
Rivaroxaban requires a higher initial dose during the first 3 weeks.
Dabigatran or edoxaban require at least 5 days of prior heparin anticoagulation.
The source material does not provide the numerical doses of these agents.
Systemic thrombolysis
Systemic thrombolytic treatment is recommended for high-risk PE. In most patients with high-risk PE, it is the preferred primary reperfusion strategy.
The principal limitation is the substantial risk of major haemorrhage, including stroke. The source material refers to thrombolytic regimens, doses, and contraindications but does not reproduce their numerical details.
Surgical pulmonary embolectomy
Surgical embolectomy is recommended when thrombolysis is contraindicated or has failed. It remains an option in:
High-risk PE
Intermediate-high-risk PE with severe RV dysfunction and clinical deterioration despite anticoagulation
Patients requiring surgical removal of a right atrial thrombus
Patients with a clot-in-transit
Patients requiring closure of a patent foramen ovale
Rescue treatment after unsuccessful thrombolysis
Outcomes are improved when surgery is undertaken before the development of vasopressor dependence, cardiogenic shock, and multisystem organ failure. Extraction should be limited to directly visible clot, and blind instrumentation of fragile pulmonary arteries should be avoided. Surgical embolectomy is most appropriately performed in experienced centres.
In an observational comparison, 30-day mortality was similar between surgery and thrombolysis, whereas thrombolysis was associated with more stroke and re-intervention. Recurrent PE requiring readmission was also more frequent after thrombolysis than after surgery, although the non-randomized design and potential selection of patients for surgery limit interpretation.
Catheter-directed treatment
Percutaneous catheter-directed treatment should be considered when thrombolysis is contraindicated or has failed, provided the necessary expertise and resources are available on site.
The source material does not provide specific device selection, procedural protocols, thrombolytic doses for catheter-based treatment, or selection criteria beyond the stated clinical indications.
Haemodynamic support
Norepinephrine and/or dobutamine should be considered in patients with high-risk PE. These agents are used as supportive treatment when circulatory compromise is present.
ECMO may be considered together with surgical embolectomy or catheter-directed treatment in patients with refractory circulatory collapse or cardiac arrest. In massive PE, venoarterial ECMO can decompress the failing RV and restore end-organ perfusion while facilitating endogenous fibrinolysis. It may be used as a bridge to embolectomy or as part of a combined reperfusion strategy.
Management of intermediate-high-risk PE
Intermediate-high-risk PE requires anticoagulation and close clinical observation because deterioration may occur despite initial haemodynamic stability. Advanced reperfusion therapy is not routine at presentation in the classification table; it is used if clinical deterioration develops.
Surgical embolectomy is an option for patients with severe RV dysfunction and clinical deterioration despite anticoagulation when thrombolysis is contraindicated. Catheter-directed treatment may also be considered in appropriate circumstances, particularly when thrombolysis has failed or cannot be given.
The source material does not provide a specific monitoring schedule, biomarker reassessment interval, or universal threshold for rescue reperfusion in intermediate-high-risk PE.
Management of intermediate-low-risk PE
Patients with intermediate-low-risk PE are treated with anticoagulation. Because only one prognostic domain—clinical risk, RV imaging, or cardiac biomarkers—is abnormal, the treatment strategy is generally anticoagulation with clinical surveillance rather than routine primary reperfusion.
The source material does not specify criteria for inpatient versus outpatient care in this group.
Management of low-risk PE
Low-risk patients should receive anticoagulation. A subset may be managed at home when reliable follow-up is ensured.
The source material does not specify the preferred anticoagulant, duration of therapy, discharge checklist, or outpatient monitoring protocol.
Guideline recommendations
The principal recommendations for acute high-risk PE are summarized below.
| Intervention | Recommendation | Class | Level of evidence |
|---|---|---|---|
| Immediate UFH, including a weight-adjusted bolus | Recommended without delay | I | C |
| Systemic thrombolysis | Recommended | I | B |
| Surgical pulmonary embolectomy when thrombolysis is contraindicated or has failed | Recommended | I | C |
| Percutaneous catheter-directed treatment when thrombolysis is contraindicated or has failed | Should be considered | IIa | C |
| Norepinephrine and/or dobutamine | Should be considered | IIa | C |
| ECMO with surgical embolectomy or catheter-directed treatment in refractory circulatory collapse or cardiac arrest | May be considered | IIb | C |
The guideline-based therapeutic framework is therefore:
High-risk PE: immediate UFH and primary reperfusion, usually systemic thrombolysis; surgery or catheter-directed treatment when thrombolysis is unsuitable or unsuccessful.
Intermediate-high-risk PE: anticoagulation and close observation, with advanced therapy if clinical deterioration occurs.
Intermediate-low-risk PE: anticoagulation.
Low-risk PE: anticoagulation, with home treatment in selected patients with dependable follow-up.
Long-term anticoagulation and recurrence risk
The duration of anticoagulation after the acute phase is influenced by the risk of recurrent venous thromboembolism after treatment is stopped. The risk categories described in the source material are:
| Estimated recurrence risk after stopping anticoagulation | Examples |
|---|---|
| Low, <3% per year | Major surgery or trauma |
| Intermediate, 3–8% per year | Minor surgery; hospitalization for acute medical illness; pregnancy or oestrogen exposure; long-haul flight; inflammatory bowel disease; autoimmune disease; no identifiable provoking factor |
| High, >8% per year | Active cancer; antiphospholipid syndrome |
These categories provide a framework for long-term decision-making, although the source material does not specify a universal treatment duration for each group.
Prognosis and follow-up
Early prognosis
Early prognosis is determined principally by haemodynamic status and the extent of RV injury or dysfunction. High-risk PE carries the greatest risk of early death and includes patients with shock or cardiac arrest. Among haemodynamically stable patients, the combination of clinical risk, RV dysfunction, and cardiac biomarker elevation identifies those at progressively greater risk.
Intermediate-high-risk patients require particular vigilance because they may deteriorate despite preserved initial blood pressure. The presence of both RV dysfunction and elevated troponin indicates a higher-risk subgroup than either abnormality alone.
Outcomes after advanced treatment
Surgical embolectomy outcomes are influenced by timing and pre-operative condition. In a multicentre surgical database, in-hospital mortality was 12%, with the poorest outcome among patients who had experienced pre-operative cardiac arrest, in whom mortality was 32%. These observational data should be interpreted in the context of case selection and centre expertise.
Combined ECMO and surgical therapy has been reported in patients with intermediate- and high-risk PE, including patients with cardiac arrest. In one reported series, in-hospital and 1-year survival were 93% and 91%, respectively, although these findings derive from observational experience.
Follow-up after PE
Follow-up should reassess:
Symptoms and functional status
Persistent or recurrent RV dysfunction
Evidence of chronic thromboembolic disease
The need for continued anticoagulation according to recurrence risk
Bleeding risk and the practical suitability of the selected anticoagulant
The source material emphasizes systematic follow-up after acute PE to improve recognition of chronic thromboembolic pulmonary hypertension and related long-term sequelae. It does not provide a specific follow-up timetable or detailed testing protocol.
