In a patient with normal cardiac biomarkers and no right‑ventricular dysfunction but a high Pulmonary Embolism Severity Index (PESI) score (class III‑V), should the risk be classified as intermediate‑low?

Risk Classification for PE Patients with High PESI but Normal Biomarkers and RV Function

Yes, a patient with normal cardiac biomarkers and no RV dysfunction but a high PESI score (class III-V) should be classified as intermediate-low risk. 1

Guideline-Based Classification

The 2019 ESC Guidelines explicitly address this clinical scenario and provide clear direction:

• Patients with signs of RV dysfunction or elevated cardiac biomarkers, despite a low PESI or sPESI of 0, should be classified into the intermediate-low-risk category. 1

• The reverse scenario (your question) follows the same logic: Assessment of RV by imaging or laboratory biomarkers should be considered even in the presence of a high PESI score. 1 When these additional markers are normal despite high PESI, the patient moves to intermediate-low rather than intermediate-high risk.

The Rationale Behind This Approach

The ESC guidelines base this recommendation on data from 3,295 patients showing that:

• 34% of patients with "low-risk" PESI (class I-II) or sPESI of 0 had signs of RV dysfunction on imaging. 1

• The presence of RV dysfunction carried an odds ratio of 4.19 for early death, even in clinically low-risk patients. 1

• Early mortality rates were 1.8% for RV dysfunction and 3.8% for elevated troponin—in the lower range of intermediate-risk PE. 1

This demonstrates that imaging and biomarkers provide independent prognostic information beyond clinical scores alone. 2

How the Two Systems Interact

PESI Alone vs. Combined Assessment

• PESI and echocardiography are independent predictors of adverse outcomes in multivariate analysis. 2 In the study by Becattini et al., PESI class III-IV had an OR of 3.1 and class V had an OR of 5.5 for adverse events, while RV/LV ratio independently predicted outcomes (OR 1.3 per 0.1 increase). 2

• In normotensive patients, troponin and RV dysfunction add incremental prognostic value to PESI, particularly at intermediate risk. 3

The 2026 AHA/ACC Guidelines Perspective

The most recent American guidelines introduce enhanced clinical categories that emphasize precision in severity classification through combined assessment of clinical parameters, RV function, and biomarkers. 4 This supports the integrated approach rather than relying on PESI alone.

Practical Algorithm for Risk Stratification

Step 1: Assess hemodynamic stability

• Shock/hypotension present = High risk (regardless of other factors) 1

Step 2: If hemodynamically stable, calculate PESI/sPESI 1

Step 3: Assess RV function (echocardiography or CTPA) AND cardiac biomarkers (troponin, NT-proBNP) 1

Step 4: Classify based on combined findings:

• High PESI + Normal RV + Normal biomarkers = Intermediate-LOW risk 1
• High PESI + Abnormal RV OR elevated biomarkers = Intermediate-HIGH risk 1
• Low PESI + Normal RV + Normal biomarkers = LOW risk 1
• Low PESI + Abnormal RV OR elevated biomarkers = Intermediate-LOW risk 1

Critical Pitfalls to Avoid

Don't Rely on PESI Alone in Either Direction

• PESI may underestimate short-term mortality risk in patients with RV dysfunction by a two-fold order of magnitude. 5 The presence of RV dysfunction alone may be sufficient for identifying higher-risk patients requiring closer monitoring.

• Conversely, high PESI without objective cardiac dysfunction may overestimate immediate risk, as the clinical variables in PESI (age, comorbidities, vital signs) reflect overall patient frailty rather than acute PE severity specifically. 3

The Importance of Both Biomarkers

When RV dysfunction is present, patients with two elevated cardiac biomarkers (troponin AND NT-proBNP) have significantly worse outcomes than those with only one biomarker (HR 3.3). 6 This suggests that within the intermediate-high category, further substratification is clinically meaningful.

Clinical Implications

For your patient (high PESI, normal biomarkers, no RV dysfunction):

• Hospital admission is recommended (not suitable for outpatient management like true low-risk PE) 1
• Standard anticoagulation is appropriate (no indication for thrombolysis or advanced therapies) 1
• The high PESI reflects comorbidity burden and overall clinical complexity rather than acute PE severity 3
• Monitor for clinical deterioration, but aggressive reperfusion strategies are not indicated 1

The intermediate-low classification appropriately balances the patient's clinical complexity (high PESI) against the absence of acute cardiac dysfunction, guiding toward conservative management with appropriate monitoring rather than escalation to advanced therapies.