OPtimal TIming for Reperfusion in Acute Pulmonary Embolism: Rationale and design of the OPTIRAPE registry.

BACKGROUND: The optimal timing of reperfusion therapy in acute pulmonary embolism (PE) remains uncertain, despite guideline recommendations supporting urgent intervention in high-risk and selected intermediate-high-risk presentations. OBJECTIVE: The OPTIRAPE registry (Optimal Timing for Reperfusion in Acute Pulmonary Embolism) aims to evaluate the association between reperfusion timing and in-hospital outcomes and to characterize real-world treatment patterns and system-related delays in patients undergoing systemic thrombolysis (ST) or catheter-directed therapies (CDTs). DESIGN AND INTERVENTIONS: OPTIRAPE (NCT07436702) is a prospective, multicentre, observational registry enrolling consecutive adults with acute high-risk or intermediate-high-risk PE undergoing ST or CDTs reperfusion therapy across seven Italian hospitals with 24/7 access to advanced imaging and reperfusion strategies. Treatment decisions are based on the 2019 European Society of Cardiology guidelines and local practice, without protocol-mandated interventions. STUDY OUTCOMES: The primary exposure is time-to-reperfusion, defined as the interval from diagnostic confirmation of high-risk PE, or, in intermediate-high-risk patients, from clinical deterioration to initiation of reperfusion therapy. The primary endpoint is in-hospital mortality. Secondary endpoints include major bleeding, early haemodynamic deterioration, need for mechanical circulatory or respiratory support, recurrent venous thromboembolism, intensive care unit admission, and length of hospital stay. IMPLICATION: OPTIRAPE will provide granular real-world data on reperfusion timing, treatment modality, and inter-hospital variability in severe PE management. It will quantify the relationship between treatment delays and in-hospital outcomes and explore potential time thresholds associated with improved survival, informing future guideline recommendations and supporting the implementation of standardized, time-sensitive reperfusion pathways in acute PE.