452. Risk stratification in Acute Pulmonary Embolism with Dr. Stavros Konstantinides

CardioNerds (Dr. Billy-Joe Mullinax, Dr. Dinu Balanescu, and Dr. Jane Ehret) discuss risk stratification in acute pulmonary embolism with Dr. Stavros Konstantinides, Chair of the 2019 ESC Pulmonary Embolism Guidelines. Using a real-world case, this episode explores how modern PE care has moved beyond “massive” and “submassive” labels toward a dynamic, physiology-based approach. The discussion highlights the limitations of static risk scores, the importance of right ventricular dysfunction and biomarkers, and why normotension does not imply stability. Special emphasis is placed on intermediate-high risk PE, early identification of impending hemodynamic collapse, and the role of lactate, serial reassessment, and PERT teams in guiding escalation of care. Audio editing by CardioNerds intern, Joshua Khorsandi.
The 2026 American multi-society PE guidelines were published after this episode was recorded.

Dr. Dinu Balanescu and Dr. Billy-Joe Mullinax are Co-chairs for the CardioNerds PE Series, developed in collaboration with the PERT Consortium.  

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls

1. Stable blood pressure does not mean low risk in PE
   Hypotension is a late finding. Patients may have severe RV failure, hypoxia, and tissue hypoperfusion while remaining normotensive — a key concept behind “normotensive shock.”
2. Risk stratification in PE must be dynamic, not static
   Legacy scores like PESI and Bova provide a snapshot and predict 30-day mortality, but they do not capture short-term trajectory or impending hemodynamic collapse.
3. Intermediate-high risk PE is a dangerous and heterogeneous group
   Patients with RV dysfunction, positive biomarkers, tachycardia, hypoxemia, and elevated lactate may have in-hospital mortality approaching 15%, rivaling STEMI.
4. Lactate is a critical but underutilized marker in PE
   Elevated lactate reflects tissue hypoxia and early circulatory failure and may identify patients at risk for collapse before blood pressure declines.
5. PERT enables physiology-driven, patient-centered PE care
   PERT teams operationalize continuous reassessment, integrate imaging, labs, and clinical trajectory, and allow timely escalation — shifting PE management from rigid categories to real-time decision-making.

Notes

Drafted by Dr. Jane Ehret.

1. What is the contemporary framework for risk stratification in acute pulmonary embolism?

• Modern PE risk stratification prioritizes hemodynamics and right ventricular (RV) function rather than clot burden.
• The 2019 ESC Guidelines classify PE into high risk, intermediate risk (low vs high), and low risk, based on: Hemodynamic status, RV dysfunction on imaging, and Cardiac biomarkers.
• This framework emphasizes early mortality risk but requires clinical context to guide escalation decisions.

2. Why is normotension insufficient to define “stability” in PE?

• Blood pressure is a late marker of circulatory failure in PE.
• Patients can maintain normal BP through Tachycardia, Increased sympathetic tone, and RV compensation.
• Many patients with preserved BP may already have shock physiology, including hypoxemia, elevated lactate, and RV failure — sometimes referred to as “normotensive shock.”

3. How should intermediate-risk PE be conceptualized clinically?

• Intermediate-risk PE is heterogeneous, ranging from patients who do well on anticoagulation to those who deteriorate rapidly.
• Intermediate-high risk PE is defined by RV dysfunction on imaging and positive cardiac biomarkers.
• Clinical features such as tachycardia, increasing oxygen requirement, and elevated lactate identify patients at highest risk within this group.

4. What are the strengths and limitations of commonly used PE risk scores?

• Legacy scores are useful for initial risk categorization but are static and limited in predicting short-term deterioration.
• Most scores were developed to predict mortality or complications at fixed time points rather than dynamic clinical trajectory.

5. What are the commonly used risk scores and clinical tools in PE, and what is each designed to predict?

• ESC Risk Stratification Algorithm: Identifies high-risk PE by hemodynamics. Uses PESI or sPESI in normotensive patients to distinguish low-risk from non–low-risk PE. Uses RV dysfunction and biomarkers to differentiate intermediate-low from intermediate-high risk. Forms the basis of many institutional PE pathways.
• PESI and sPESI: Validated to predict 30-day mortality. Widely used to identify low-risk patients appropriate for outpatient management. Heavily influenced by age and comorbidities.
• Bova Score: Predicts 30-day PE-related complications in normotensive patients.
• Composite PE Shock Score (CPES): Predicts normotensive shock in hemodynamically stable PE patients.
• Pulmonary Embolism Progression (PEP) Score: Predicts progression from intermediate-risk to high-risk PE within 72 hours of diagnosis.
• PE Short-term Clinical Outcomes Risk Estimation (PE-SCORE): Predicts clinical deterioration or death within 5 days of PE diagnosis.
• Hestia Criteria: Identifies low-risk PE patients safe for outpatient treatment.
• Wells’ Criteria and Revised Geneva Score: Determine pretest probability for diagnostic triage.
• PERC Score: Rules out PE in very low-risk patients.

6. What is the role of biomarkers in PE risk stratification?

• Troponin and natriuretic peptides reflect RV myocardial injury and strain.
• Current guidelines treat biomarkers as binary (positive vs negative), despite risk being continuous.
• Biomarkers are most helpful for: Initial risk classification.
• They are less useful for: Short-interval monitoring and Detecting rapid clinical deterioration.

7. Why is lactate an important physiologic marker in PE?

• Lactate reflects global tissue hypoxia and impaired perfusion.
• Elevated lactate may identify patients with: Early circulatory failure and Increased risk of imminent hemodynamic collapse.
• Lactate is not currently included in ESC risk algorithms but may add important prognostic information in intermediate-risk patients.

8. How does trajectory influence decision-making in PE management?

• Risk stratification should be viewed as a dynamic process, not a one-time label.
• Worsening clinical trajectory may include: Rising heart rate, Increasing oxygen needs, Rising lactate, and Progressive RV dysfunction.
• Serial reassessment is essential for timely escalation of care.

9. What role do Pulmonary Embolism Response Teams (PERT) play in risk stratification?

• PERT facilitates: Multidisciplinary decision-making and Integration of imaging, biomarkers, and clinical physiology.
• PERT is most valuable for: Intermediate-risk and high-risk PE and Patients with complex comorbidities or uncertain trajectory.
• PERT enables a shift from category-based to physiology-driven PE care.

References

1. Konstantinides SV, Meyer G, Becattini C, 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;54(3):1901647. Published 2019 Oct 9. doi:10.1183/13993003.01647-2019

2. Leidi A, Bex S, Righini M, Berner A, Grosgurin O, Marti C. Risk Stratification in Patients with Acute Pulmonary Embolism: Current Evidence and Perspectives. J Clin Med. 2022;11(9):2533. Published 2022 Apr 30. doi:10.3390/jcm11092533

3. Choi WH, Kwon SU, Jwa YJ, et al. The pulmonary embolism severity index in predicting the prognosis of patients with pulmonary embolism. Korean J Intern Med. 2009;24(2):123-127. doi:10.3904/kjim.2009.24.2.123

4. Jiménez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15):1383-1389. doi:10.1001/archinternmed.2010.199

5. Chen X, Shao X, Zhang Y, et al. Assessment of the Bova score for risk stratification of acute normotensive pulmonary embolism: A systematic review and meta-analysis. Thromb Res. 2020;193:99-106. doi:10.1016/j.thromres.2020.05.047

6. Zhang RS, Yuriditsky E, Zhang P, et al. Composite Pulmonary Embolism Shock Score and Risk of Adverse Outcomes in Patients With Pulmonary Embolism. Circ Cardiovasc Interv. 2024;17(8):e014088. doi:10.1161/CIRCINTERVENTIONS.124.014088

7. Zhang RS, Alam U, Sharp ASP, et al. Validating the Composite Pulmonary Embolism Shock Score for Predicting Normotensive Shock in Intermediate-Risk Pulmonary Embolism. Circ Cardiovasc Interv. 2024;17(2):e013399. doi:10.1161/CIRCINTERVENTIONS.123.013399

8. Ehret J, Wakefield D, Badlam J, Antkowiak M, Erdreich B. Development of the Pulmonary Embolism Progression (PEP) score for predicting short-term clinical deterioration in intermediate-risk pulmonary embolism: a single-center retrospective study. J Thromb Thrombolysis. 2025;58(2):243-253. doi:10.1007/s11239-024-03051-5

9. Weekes AJ, Raper JD, Lupez K, et al. Development and validation of a prognostic tool: Pulmonary embolism short-term clinical outcomes risk estimation (PE-SCORE). PLoS One. 2021;16(11):e0260036. Published 2021 Nov 18. doi:10.1371/journal.pone.0260036

10. Zondag W, Hiddinga BI, Crobach MJ, et al. Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism. Eur Respir J. 2013;41(3):588-592. doi:10.1183/09031936.00030412

11. Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001;135(2):98-107. doi:10.7326/0003-4819-135-2-200107170-00010

12. Wolf SJ, McCubbin TR, Feldhaus KM, Faragher JP, Adcock DM. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med. 2004;44(5):503-510. doi:10.1016/j.annemergmed.2004.04.002

13. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144(3):165-171. doi:10.7326/0003-4819-144-3-200602070-00004

14. Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2(8):1247-1255. doi:10.1111/j.1538-7836.2004.00790.x

15. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6(5):772-780. doi:10.1111/j.1538-7836.2008.02944.x