Integrated management of acute pulmonary embolism and the post-pulmonary embolism syndrome: risk stratification, modern therapies, and long-term follow-up

Abstract

Pulmonary embolism (PE) is increasingly recognized as an episode of care that extends well beyond hospital discharge. Current guidance is distributed across several documents: the 2019 European Society of Cardiology (ESC) guidelines; the 2026 American Heart Association/American College of Cardiology (AHA/ACC) multisociety guideline, which replaced the massive/submassive terminology with clinical categories A–E; and separate position papers on catheter-directed intervention (CDI) and on follow-up. This narrative review (i) provides a side-by-side comparison of the ESC and AHA/ACC risk frameworks and their therapeutic implications; (ii) updates the evidence on reperfusion, including the recent randomized trials HI-PEITHO, PEERLESS and STORM-PE; and (iii) focuses on transitions of care and long-term follow-up, which guidelines address less comprehensively. Anticoagulation, preferably with a direct oral anticoagulant, remains the treatment for most patients. Systemic thrombolysis is reserved for high-risk (ESC) or category E (AHA/ACC) PE, because in intermediate-risk disease it halves hemodynamic decompensation at the cost of a several-fold increase in major and intracranial bleeding, without long-term functional benefit. In HI-PEITHO, ultrasound-facilitated catheter-directed thrombolysis reduced a 7-day composite outcome driven by cardiorespiratory decompensation (4.0% vs. 10.3%) in intermediate-high-risk patients with additional markers of physiological stress, without intracranial hemorrhage; a survival benefit of CDI has not been demonstrated. At discharge, a minimum bundle should specify the drug, dose, anticipated duration, provoking context, bleeding mitigation and follow-up ownership, followed by early contact within one week and a structured review at approximately three months. Up to half of survivors report persistent dyspnea or exercise limitation, whereas chronic thromboembolic pulmonary hypertension (CTEPH) develops in approximately 2%–3%. Persistent symptoms should prompt phenotype-directed evaluation with echocardiography, ventilation/perfusion scintigraphy, cardiopulmonary exercise testing and, when indicated, right-heart catheterization interpreted with the 2022 hemodynamic definitions, followed by early referral to an expert center where pulmonary endarterectomy, balloon pulmonary angioplasty and medical therapy can be combined. We state the type of evidence underpinning each key recommendation, propose a discharge bundle, a structured follow-up algorithm and episode-wide quality indicators, and identify the evidence gaps that should guide future trials.