Recent advances in risk stratification and treatment of acute pulmonary embolism

Table 1 Comparison of risk stratification models and parameters in acute pulmonary embolism

Ref.	Risk model/marker	Clinical application	Clinical use	Statistical performance	Advantages	Limitations
Aujesky et al[23], 2005	PESI	30-day mortality	Risk stratification for 30-day mortality	95% sensitivity, 38% specificity (for PE mortality)[24]	Only clinical assessment	Multiple parameters, no assessment of RV strain, low specificity
Jiménez et al[25], 2010	sPESI	30-day mortality, 30-day recurrent VTE/PE or bleeding	Simpler alternative to PESI	96% sensitivity, 37% specificity (for PE mortality)[24]	Simple and fast	No assessment of RV strain, low specificity
Zondag et al[26], 2011	Hestia criteria	Low-risk patients identification	Determines eligibility for outpatient management	82% sensitivity, 56% specificity (low-risk identification)[27]	99% negative prognostic value, solid validation data	Only low-risk assessment
Bova et al[28], 2014	BOVA score	30-day clinical deterioration and mortality	Identifies patients who may need escalated care	AUROC = 0.73, 95%CI: 0.68-0.77 (PE complication prediction)	Incorporates RV dysfunction, separates normotensive PE SBP > 90 mmHg from > 100 mmHg	Requires imaging and blood tests
Vanni et al[29], 2013	Plasma lactate	Clinical deterioration and 30-day mortality	Helps identify normotensive shock	HR = 11.67; 95%CI: 3.32-41.03 (all cause 30-day mortality)	Identifies hypoperfusion, thus true hemodynamic impact	Used supplementary to enhance risk models, requires sequential ABG assessment
Otero et al[30], 2007	Shock index	30-day mortality	Used in risk stratification for hemodynamic instability	SI vs SBP < 90 mmHg; specificity: 86.3% vs 96.6%, sensitivity: 30.5% vs 7.9%	Improves hemodynamic assessment	Lower specificity compared to SBP < 90 mmHg, limited value in hypertensive patients
Grade Santos et al[31], 2022	NEWS score	Clinical deterioration and 30-day mortality	Used in hospitalized patients for early detection of worsening PE	Greater predictive power compared to PESI (OR = 1.35; 95%CI: 1.11-1.64, P = 0.003 vs OR = 1.02; 95%CI: 1.00-1.03, P = 0.03)	Already widely used and validated in various health systems	Not specific for PE
Meinel et al[32], 2015	RV/LV ratio (CTPA)	Mortality and adverse outcomes up to 6 months	Predicts PE outcomes by RV dysfunction assessment	All-cause mortality (OR = 2.5; 95%CI: 1.8-3.5)	Calculated from CTPA if echocardiography is not available	Requires imaging
Pruszczyk et al[33], 2014	TAPSE	30-day mortality or need for rescue thrombolysis	Predicts PE outcomes by RV dysfunction assessment	Better AUC compared to RV/LV ratio (0.91, 95%CI: 0.856-0.935; P = 0.0001 vs 0.638, 95%CI: 0.589-0.686; P = 0.001)	Single parameter compared to RV/LV	Requires echocardiography
Kiamanesh et al[34], 2022	TAPSE/PASP ratio (RV-PA uncoupling)	Adverse events in normotensive PE	Predicts PE outcomes by RV-PA uncoupling	For each 0.1 mm/mmHg decrease in TAPSE/PASP (adjust OR = 2.49, 95%CI: 1.46-4.24, P = 0.001)	Allows the assessment of the true hemodynamic impact of PE in RV function	Requires echocardiography, limited evidence in PE

PESI: Pulmonary embolism severity index; sPESI: Simplified pulmonary embolism severity index; NEWS: National Early Warning Score; TAPSE: Tricuspid annular plane systolic excursion; PE: Pulmonary embolism; VTE: Venous thromboembolism; TAPSE: Tricuspid annular plane systolic excursion; PASP: Pulmonary artery systolic pressure; RV: Right ventricle; RV/LV ratio: Right ventricular to left ventricular diameter ratio; PA: Pulmonary artery; OR: Odds ratio; HR: Hazard ratio; CI: Confidence interval; AUROC: Area under the receiver operating characteristic curve; CTPA: Computed tomography pulmonary angiogram; SBP: Systolic blood pressure.

Table 2 Major trials of interventional treatment for acute pulmonary embolism[48]

Ref.	Trial name	Device	Design	Population	Pe risk category	Intervention	Control	Outcomes	Follow up
[9]	FLARE, 2019	FlowTriever	Single-arm	106	Intermediate-risk, PE	Anticoagulation plus FlowTriever	-	∆RV/LV ratio at 48 hours: 0.41 ± 0.05 (P < 0.0001)/0 all-cause deaths/major bleeding: 0.9% at 48 hours	30 days
[11]	EXTRACT-PE, 2021	Indigo	Single-arm	119	Intermediate-risk	Anticoagulation plus Indigo	-	∆RV/LV ratio at 48 hours: 0.43 ± 0.26 (P < 0.0001)/all-cause death: 1.1%; major bleeding: 1.6% at 48 hours	30 days
[13]	SEATTLE II, 2015	EkoSonic	Single-arm	150	Intermediate high-risk PE	Anticoagulation plus tPA-USAT (12-24 mg)	-	∆RV/LV ratio at 48 hours: 0.42 ± 0.36 (P < 0.0001)/7 deaths, 15 major bleeds at 30 days	30 days
[10]	OPTALYSE PE, 2018	EkoSonic	Randomised, open-label	101	Intermediate high-risk PE	Anticoagulation plus tPA-USAT (4 mg, 6 mg, or 12 mg)	Compared 4 tPA regimens	RV/LV ratio reduced in all arms at 48 hours/5 major bleeds at 72 hours	365 days
[14]	FLAME, 2023	FlowTriever	Prospective, non-randomised	104	High-risk PE	Anticoagulation plus FlowTriever	Other therapies	Composite of all-cause mortality, clinical deterioration, bailout, and major bleeding: 17% vs 63.9%/all-cause death: 1.9% vs 29.5%; major bleeding: 11.3% vs 24.6%	In hospital
[46]	PEERLESS, 2024	FlowTriever	Open-label	550	Intermediate high-risk PE	FlowTriever	Catheter directed thrombolysis	Primary composite win ratio: 5.01 (P < 0.001) driven by fewer clinical deteriorations and reduced ICU utilization/all-cause death: 0% at discharge/no increase in ICH or major bleeding	7 days

PE: Pulmonary embolism; LV: Left ventricular; RV: Right ventricular; tPA: Tissue plasminogen activator; USAT: Ultrasound-assisted thrombolysis; ICU: Intensive care unit; ICH: Intracranial bleeding.

Table 3 Suggested optimal follow-up algorithm in pulmonary embolism

Time point	Assessments/actions	Key considerations/notes
Index event	Baseline clinical assessment. Perform cancer screening (clinical exam, basic labs, chest imaging via CTPA). Bleeding and CV risk assessments	Imaging (e.g., CTPA) is typically available. Begin addressing reproductive considerations for female patients where applicable
4-6 weeks	Conduct follow-up visit(s) for continued bleeding risk assessment. Reassess CV risk. Plan for thrombophilia screening (deferred until 4-6 weeks to avoid false results, especially if on DOACs)	Adjust anticoagulation treatment based on modifiable bleeding risk factors. Thrombophilia screening (especially for antiphospholipid syndrome) should be considered in unprovoked cases
At 3 months	Evaluate functional status and quality of life. Perform CPET if symptoms persist. Screen for post-PE syndrome (new/progressive dyspnea, exercise intolerance). Assess for CTEPH in patients with persistent symptoms	Post-PE syndrome may affect 40%-60% of survivors. CTEPH (affecting 2%-3%) should be ruled out in patients with ongoing dyspnea or right heart failure; referral to expert centers is advised
Long-term follow-up	Periodic follow-up visits: Bleeding and CV risk assessment. Monitor for long-term complications (post-PE syndrome, CTEPH). Provide tailored management for female patients (pregnancy planning, contraceptive guidance). Advise on gradual resumption of physical activity and appropriate travel (e.g., use compression stockings and on-demand prophylactic anticoagulation for long air travel when indicated)	Lifestyle counseling remains crucial for recovery. Regular monitoring ensures timely intervention for evolving complications

CTPA: Computed tomography pulmonary angiogram; CV: Cardiovascular; DOACs: Direct oral anticoagulants; CPET: Cardiopulmonary exercise testing; CTEPH: Chronic thromboembolic pulmonary hypertension.