Derivation and Validation of Multimarker Prognostication for Normotensive Patients with Acute Symptomatic Pulmonary Embolism
David Jiménez 1, Dita Kopecna 1, Victor Tapson 2, Beau Briese 3, Donald Schreiber 3, José Luis Lobo 4, Manuel Monreal 5, Drahomir Aujesky 6, Olivier Sanchez 7, Guy Meyer 7, Stavros Konstantinides 8, Roger D. Yusen 9, the PROTECT investigators.
1 Respiratory Department, Ramón y Cajal Hospital, IRYCIS, Madrid, Spain
2 Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, USA
3 Division of Emergency Medicine, Stanford University School of Medicine, Palo Alto, California, USA
4 Respiratory Department, Txagorritxu Hospital, Vitoria, Spain
5 Medicine Department, Germans Trias I Pujol Hospital, Badalona, Spain
6 Division of General Internal Medicine, Bern University Hospital, Bern, Switzerland
7 Université Paris Descartes, Sorbonne Paris Cité; Division of Respiratory and Intensive Care Medicine, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
8 Center for Thrombosis and Hemostasis, University of Mainz, Germany
9 Divisions of Pulmonary and Critical Care Medicine and General Medical Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
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 study (derivation cohort), and 529 patients from the PREP study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, haemodynamic 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 (sPESI), cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and lower limb ultrasound testing (CCUS). The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the sPESI and BNP 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 that have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, haemodynamic collapse, and/or recurrent PE within the following 30 days.
Am J Respir Crit Care Med. 2014 Jan 28. [Epub ahead of print]
Methods: The study retrospectively developed a simplified PESI clinical prediction rule for estimating the risk of 30-day mortality in a derivation cohort of Spanish outpatients. Simplified and original PESI performances were compared in the derivation cohort. The simplified PESI underwent retrospective external validation in an independent multinational cohort (Registro Informatizado de la Enfermedad Tromboembólica [RIETE] cohort) of outpatients.
Simplification of the Pulmonary Embolism Severity Index for Prognostication in Patients With Acute Symptomatic Pulmonary Embolism
David Jiménez, MD, PhD; Drahomir Aujesky, MD; Lisa Moores, MD; Vicente Gómez, MD; José Luis Lobo, MD, PhD; Fernando Uresandi, MD, PhD; Remedios Otero, MD, PhD; Manuel Monreal, MD, PhD; Alfonso Muriel, MSc; Roger D. Yusen, MD; RIETE Investigators
Background: The Pulmonary Embolism Severity Index (PESI) estimates the risk of 30-day mortality in patients with acute pulmonary embolism (PE). We constructed a simplified version of the PESI.
Results: In the derivation data set, univariate logistic regression of the original 11 PESI variables led to the removal of variables that did not reach statistical significance and subsequently produced the simplified PESI that contained the variables of age, cancer, chronic cardiopulmonary disease, heart rate, systolic blood pressure, and oxyhemoglobin saturation levels. The prognostic accuracy of the original and simplified PESI scores did not differ (area under the curve, 0.75 [95% confidence interval (CI), 0.69-0.80]). The 305 of 995 patients (30.7%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.0% (95% CI, 0.0%-2.1%) compared with 10.9% (8.5%-13.2%) in the high-risk group. In the RIETE validation cohort, 2569 of 7106 patients (36.2%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.1% (95% CI, 0.7%-1.5%) compared with 8.9% (8.1%-9.8%) in the high-risk group.
Conclusion: The simplified PESI has similar prognostic accuracy and clinical utility and greater ease of use compared with the original PESI.
Arch Intern Med. 2010;170(15):1383-1389. doi:10.1001/archinternmed.2010.199.