Identifying the spectrum of clinical trajectories in intermediate-high risk pulmonary embolism: A clinical and research imperative

AbstractIntermediate-high-risk pulmonary embolism (PE) is characterized by broad clinical, physiologic, and hemodynamic parameters, but its prognostic trajectory is poorly described by current risk stratification tools. New clinical scoring systems and echocardiographic indices have gained attention for their improved capacity to anticipate disease progression and predict clinical decompensation, particularly within the first 72 h or up to 7 days of diagnosis despite systemic anticoagulation. This growing evidence-base underscores the importance of clinical phenotype to determine the management approach, as well as early referral to specialized centers with access to pulmonary embolism response teams (PERTs) and the capacity to provide advanced reperfusion strategies, including systemic thrombolysis, catheter-directed therapy, surgical embolectomy, and mechanical circulatory support when indicated. This review provides a critical appraisal of the literature regarding the management of intermediate-high-risk PE, highlighting prognostic factors, phenotype-driven therapeutic approaches, emerging biomarkers, and existing gaps in evidence, to gain perspective on the spectrum of clinical trajectories for such patients.