Overview
Acute pulmonary embolism (PE) is a leading cardiovascular cause of emergency department admission and mortality worldwide. While existing registries have described general epidemiological trends and outpatient anticoagulation patterns, there remains a critical evidence gap regarding granular clinical presentation, acute pre-hospital and emergency care, dynamic bedside reassessment, and their direct impact on long-term patient outcomes.
The PERSEUS Registry (Pulmonary Embolism Registry from Short-term Emergency to long-term follow-Up and Surveillance) is an academic, investigator-initiated, multicenter, ambispective (combining retrospective and prospective cohorts), non-interventional observational registry. Promoted by Azienda Ospedaliero-Universitaria Careggi (Florence, Italy) in collaboration with a national and international hospital network, the registry enrolls consecutive adult patients presenting with objectively confirmed acute PE across emergency departments, high-dependency units, and inpatient wards.
The primary objective of PERSEUS is to systematically characterize real-world clinical management and major adverse outcomes across the entire continuum of care-from pre-hospital and initial emergency department triage through dynamic in-hospital serial reassessment (T1-T4 intervals) and long-term follow-up (up to 5 years).
The registry provides an extensive, high-quality centralized data infrastructure to:
- Determine the contemporary incidence of 30-day all-cause and PE-related mortality, hemodynamic decompensation, recurrent venous thromboembolism (VTE), major bleeding (according to ISTH criteria), and chronic thromboembolic pulmonary hypertension (CTEPH);
- Externally validate and compare clinical risk-stratification models and prognostic scoring systems (including the TELOS-plus score, simplified PESI, Bova score, ESC 2019 guidelines, and the AHA/ACC 2026 clinical classification);
- Evaluate the real-world clinical effectiveness and safety of reperfusion therapies (systemic thrombolysis, catheter-directed therapies, and surgical embolectomy) in normotensive intermediate-high risk and hemodynamically unstable patients.
Being strictly observational and non-interventional, patient management is conducted entirely according to routine clinical practice, local protocols, and international clinical guidelines, with no study-mandated interventions or diagnostic tests.
Description
BACKGROUND AND SCIENTIFIC RATIONALE Pulmonary embolism (PE) represents a major cause of emergency department (ED) presentation, critical care admission, and early mortality. Despite advances in diagnostic algorithms and therapeutic strategies, intermediate- and high-risk PE patients remain challenging to risk-stratify dynamically during the acute phase. Current prognostic tools often rely solely on baseline single-point parameters, neglecting acute pathophysiological changes during the initial 48 hours of treatment. The PERSEUS Registry is designed to bridge this gap by capturing comprehensive, granular real-world data spanning the acute presentation, dynamic in-hospital course, and long-term surveillance.
STUDY DESIGN AND COHORTS
PERSEUS is an observational, ambispective, multicenter registry comprising two distinct phases:
- Retrospective Phase (Historical Cohort): Includes consecutive adult patients diagnosed with acute PE from January 1, 2023, up to the date of local Ethics Committee approval at each participating site.
- Prospective Phase (Contemporary Cohort): Enrolls consecutive adult patients presenting with acute PE following institutional Ethics Committee approval, extending for a continuous enrollment period of 5 years.
STUDY SETTING AND CLINICAL CONTINUUM OF CARE
Data collection spans the entire continuum of clinical care across participating academic, tertiary, and regional hospitals:
- Baseline Presentation (T0): Captures pre-hospital emergency medical service (EMS) data (initial vital signs, cardiac arrest, point-of-care ultrasound \[POCUS\], pre-hospital anticoagulation or thrombolysis), ED arrival parameters, clinical symptoms, arterial blood gas analysis, admission laboratory biomarkers (high-sensitivity troponin, BNP/NT-proBNP, lactate, D-dimer, renal function), electrocardiographic patterns, and multiorgan diagnostic imaging (CT pulmonary angiography \[CTPA\], complete echocardiography/POCUS, and compressive venous ultrasound \[CUS\]).
- Dynamic In-Hospital Reassessment (T1-T4): To capture real-world hemodynamic and respiratory trajectories, serial parameters documented during standard clinical monitoring are recorded across predefined temporal windows: T1 (3-6 hours), T2 (6-12 hours), T3 (12-24 hours), and T4 (24-48 hours). Parameters include serial vital signs, shock index, respiratory support modalities, serial lactate/troponin kinetics, echocardiographic right ventricular function changes, and need for escalating hemodynamic support (vasopressors, inotropes, non-invasive ventilation, mechanical ventilation, or ECMO).
- Hospital Discharge \& Complications: Documents in-hospital adverse events, need for rescue reperfusion, procedural complications, bleeding events, length of stay, and vital status at discharge.
- Follow-up Surveillance: Structured evaluations at 30 days, 3 months, 12 months, and annually thereafter up to 5 years, evaluating all-cause survival, adjudicated cause of death, VTE recurrence, major and clinically relevant non-major bleeding, persistent functional limitations (Modified Rankin Scale, dyspnea), and the development of Chronic Thromboembolic Pulmonary Hypertension (CTEPH).
ENDPOINTS AND DEFINITIONS
- Primary Endpoint: Real-world clinical management and major adverse outcomes, evaluated by the incidence of 30-day all-cause mortality and PE-related mortality. Fatal PE is adjudicated using standardized criteria as death directly attributable to objectively confirmed index or recurrent PE, cardiac arrest/obstructive shock due to PE, or death without alternative identifiable competing causes.
- Secondary Endpoints: Recurrent confirmed VTE (PE or deep vein thrombosis); major bleeding defined according to International Society on Thrombosis and Haemostasis (ISTH) criteria (fatal, in a critical site, or associated with a hemoglobin fall \>=2 g/dL or transfusion of \>=2 units of packed red blood cells); clinically-relevant non-major bleeding (CRNMB); early hemodynamic decompensation; and long-term incidence of post-PE syndrome and CTEPH.
DATA MANAGEMENT, QUALITY ASSURANCE, AND ETHICAL GOVERNANCE Data collection is centralized using an electronic Case Report Form (eCRF) deployed on the REDCap (Research Electronic Data Capture) platform hosted on secure institutional servers at Azienda Ospedaliero-Universitaria Careggi (Florence, Italy).
- Privacy and Data Segregation: Strict GDPR compliance is maintained. Patient data are pseudonymized at source by the local site investigator using site-specific Subject IDs. The decoding key linking the alphanumeric ID to personal identifiers is maintained exclusively at the local participating hospital under the responsibility of the local Principal Investigator.
- Data Access Groups (DAGs): REDCap DAGs are enforced to compartmentalize site-level access, ensuring participating centers can exclusively view, enter, and edit their own cohort's records, with no unauthorized cross-center data visibility.
- Regulatory Framework: The registry protocol and centralized data architecture have been formally approved by the coordinating Ethics Committee (Comitato Etico Regione Toscana - Area Vasta Centro, CEAVC, approval reference 30742\_oss) and conducted in accordance with the Declaration of Helsinki, Good Clinical Practice principles, and applicable privacy regulations (including Article 110-bis of the Italian Privacy Code).
Eligibility
Inclusion Criteria:
- Age 18 years or older at the time of presentation.
- Objectively confirmed diagnosis of acute pulmonary embolism (PE), with or without concomitant deep vein thrombosis (DVT) of the lower or upper extremities, confirmed by at least one of the following methods:
- Computed tomography pulmonary angiography (CTPA) demonstrating intraluminal filling defects in the pulmonary arterial tree;
- Ventilation/perfusion (V/Q) lung scintigraphy demonstrating high-probability mismatch;
- Conventional catheter-directed pulmonary angiography;
- In hemodynamically unstable patients (obstructive shock or cardiac arrest) where transport for definitive imaging is unsafe or unfeasible: bedside point-of-care ultrasound (POCUS) / echocardiography demonstrating acute right ventricular overload in combination with confirmed proximal DVT or mobile right heart thromboemboli.
- For the retrospective cohort: availability of medical records documenting clinical presentation and index diagnostic work-up at baseline (T0). The absence of serial reassessment timepoints (T1-T4) does not constitute an exclusion criterion.
- Written informed consent obtained from the patient or legal surrogate, or waiver/exception under Article 110-bis of the Italian Privacy Code (and applicable institutional ethical clearance) for deceased or untraceable patients.
Exclusion Criteria:
\* Current active enrollment in an interventional experimental drug trial (blinded randomized clinical trial) where active drug allocation or protocol-mandated therapeutic regimen is unknown.
