Pulmonary Embolism Registry From Short-Term Emergency to Long-Term Follow-Up and Surveillance

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

Time perspective: ambispective (retrospective and prospective cohorts, described below).

PERSEUS is an observational, ambispective, multicenter registry comprising two distinct phases:

1. 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. Data are abstracted from medical records.
2. Prospective Phase (Contemporary Cohort): Enrolls consecutive adult patients presenting with acute PE after local Ethics Committee approval, extending for a continuous enrollment period of 5 years. Data are collected during routine care.

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 compression 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 or respiratory 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: Thirty-day status is ascertained from clinical records. Follow-up then reflects routine care at 3 and 12 months and annually thereafter up to 5 years (in-person visit, telemedicine, telephone contact or review of clinical documentation), with regional mortality registries used to ascertain vital status when needed. Follow-up collects all-cause survival, cause of death, VTE recurrence, major and clinically relevant non-major bleeding, persistent functional limitation (modified Rankin Scale, exertional dyspnea, six-minute walk test when performed) and the development of chronic thromboembolic pulmonary hypertension (CTEPH).

OUTCOMES

Outcome definitions and time frames are reported in the Outcome Measures section.

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 center's records, with no unauthorized cross-center data visibility.
• Quality Assurance: The eCRF includes built-in validation rules (range and logic checks). The coordinating center performs regular central monitoring for inconsistencies, outliers and missing data, and discrepancies are resolved with each center through a formal query process. The Steering Committee reviews enrollment, data quality and protocol adherence every 6 months.
• Regulatory Framework: Protocol version 2.0 (7 May 2026) received a favourable opinion from the Comitato Etico Regione Toscana - Area Vasta Centro (CEAVC, register no. 30742_oss, meeting of 9 June 2026) for the sites of Azienda Ospedaliero-Universitaria Careggi and Azienda USL Toscana Centro. Participation of other national and international centers is subject to approval of a protocol amendment and of the competent local ethics committees. The study is 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).