Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism

Am J Respir Crit Care Med. 2014 Mar 15;189(6):718-26. doi: 10.1164/rccm.201311-2040OC.


Rationale: Not all patients with acute pulmonary embolism (PE) have a high risk of an adverse short-term outcome.

Objectives: This prospective cohort study aimed to develop a multimarker prognostic model that accurately classifies normotensive patients with PE into low and high categories of risk of adverse medical outcomes.

Methods: The study enrolled 848 outpatients from the PROTECT (PROgnosTic valuE of Computed Tomography) study (derivation cohort) and 529 patients from the Prognostic Factors for Pulmonary Embolism (PREP) study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, hemodynamic collapse, and/or adjudicated recurrent PE.

Measurements and main results: A complicated course occurred in 63 (7.4%) of the 848 normotensive patients with acute symptomatic PE in the derivation cohort and in 24 patients (4.5%) in the validation cohort. The final model included the simplified Pulmonary Embolism Severity Index, cardiac troponin I, brain natriuretic peptide, and lower limb ultrasound testing. The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the simplified Pulmonary Embolism Severity Index and brain natriuretic peptide testing showed a negative predictive value for a complicated course of 99.1 and 100% in the derivation and validation cohorts, respectively. The combination of all modalities had a positive predictive value for the prediction of a complicated course of 25.8% in the derivation cohort and 21.2% in the validation cohort.

Conclusions: For normotensive patients who have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, hemodynamic collapse, and/or recurrent PE within the following 30 days.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Biomarkers / blood
  • Blood Pressure
  • Decision Support Techniques*
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multidetector Computed Tomography
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / complications
  • Pulmonary Embolism / diagnosis*
  • Pulmonary Embolism / mortality
  • Recurrence
  • Retrospective Studies
  • Risk Assessment / methods
  • Risk Factors
  • Severity of Illness Index


  • Biomarkers