Does the location of the pulmonary embolism (PE) influence management in patients with an elevated Pulmonary Embolism Severity Index (PESI) score?

Does PE Location Matter When PESI Score is Elevated?

In patients with elevated PESI scores, the anatomic location of the PE does matter clinically, but primarily in the context of right heart thrombi and central/proximal emboli—not for routine risk stratification, which should be driven by hemodynamic status, RV dysfunction, and the PESI score itself. 1

Primary Risk Stratification Framework

The 2019 ESC Guidelines establish that risk stratification in PE is hierarchical and does not primarily depend on clot location 1:

• High-risk PE is defined by hemodynamic instability (sustained hypotension <90 mmHg, shock, or cardiac arrest), regardless of clot location 1
• Intermediate-risk PE requires both elevated PESI (Class III or higher, or sPESI ≥1) AND evidence of RV dysfunction on imaging or elevated cardiac biomarkers 1
• Low-risk PE is identified by PESI Class I-II (or sPESI=0) with no RV dysfunction 1, 2

When PESI is elevated (Class III-V), patients are automatically in at least the intermediate-risk category, and management decisions hinge on hemodynamic stability and RV function—not anatomic location per se 1.

When Location Does Matter: Specific High-Risk Anatomic Findings

Right Heart Thrombi

The presence of right heart thrombi represents a critical exception where location significantly impacts prognosis 1:

• Mortality with right heart thrombus is 21% versus 11% without (p<0.05) in the ICOPER registry 1
• In a retrospective analysis of 177 PE patients with right heart thrombus, mortality was 100% with no treatment, 28.6% with heparin alone, 23.8% with thrombolytics, and 11.3% with embolectomy 1
• Thrombolytic therapy was the only treatment independently associated with decreased mortality on multivariate analysis 1

Central vs. Peripheral Emboli

While central PE location correlates with higher clot burden, the ESC Guidelines emphasize that RV dysfunction on imaging (echocardiography or CTPA) is more prognostically relevant than anatomic location alone 1:

• RV dilation on CTPA (RV/LV diameter ratio >0.9) independently predicts adverse outcomes 1
• Recent research confirms that among normotensive PE patients with RV involvement, PESI score predicts adverse outcomes better than anatomic considerations, with primary outcome rates increasing from 4.2% (PESI I) to 23.1% (PESI V) 3

Clinical Algorithm for Elevated PESI Patients

When PESI is elevated (≥Class III or sPESI ≥1), follow this approach 1:

1. Assess hemodynamic stability immediately

   • If unstable (hypotension, shock): High-risk PE → systemic thrombolysis indicated 1
   • If stable: Proceed to step 2

2. Evaluate for RV dysfunction (via echocardiography or CTPA) 1

   • Specifically look for right heart thrombi on echocardiography, as this finding may warrant more aggressive therapy even in normotensive patients 1
   • Assess RV/LV ratio on CTPA (>0.9 indicates dysfunction) 1

3. Measure cardiac biomarkers (troponin, NT-proBNP) 1

   • NT-proBNP ≥600 pg/mL indicates elevated risk 1
   • Elevated troponin indicates myocardial injury 1

4. Classify into intermediate-high vs. intermediate-low risk 1:

   • Intermediate-high: Elevated PESI + RV dysfunction + positive biomarkers → Inpatient monitoring, consider rescue thrombolysis if deterioration 1
   • Intermediate-low: Elevated PESI + only one (or neither) of RV dysfunction/biomarkers → Inpatient management with anticoagulation 1

Common Pitfalls

• Overreliance on clot burden or anatomic location without assessing hemodynamics and RV function—the Miller Index (angiographic burden) has limited clinical utility 1
• Missing right heart thrombi on echocardiography, which dramatically increases mortality and may warrant thrombolysis even in normotensive patients 1
• Discharging patients with elevated PESI early based solely on imaging—14% of patients with adverse events within 5 days were categorized as low-risk by PESI in one study, highlighting the need for comprehensive assessment 4
• Failing to recognize that PESI discordance with imaging findings (e.g., PESI III with RV dysfunction) should default to intermediate-risk classification 1

Evidence Synthesis

The most recent high-quality evidence (2019 ESC Guidelines) establishes that hemodynamic status and RV dysfunction drive management decisions in elevated PESI patients, not anatomic location 1. However, the specific finding of right heart thrombus represents an important exception where location does matter prognostically and may influence the decision for thrombolytic therapy 1. Recent research confirms PESI outperforms anatomic scoring systems like BOVA for predicting adverse outcomes in normotensive PE with RV involvement (AUC 0.746 vs. 0.679) 3.