CardioNerds (Drs. Billy Joe Mullinax, Dinu Balanescu, and Saahil Jumkhawala) discuss the 2026 American Heart Association (AHA)/American College of Cardiology (ACC) multisocietal guidelines for the evaluation and management of acute pulmonary embolism (PE) with Dr. Mark Creager, Director Emeritus of the Heart and Vascular Center at Dartmouth Health, past president of the AHA, and Chair of the Writing Committee for the 2026 AHA/ACC PE Guidelines. Audio editing by CardioNerds intern, Dr. Patrick Pekyi-Boateng. Pulmonary embolism is one of the most rapidly evolving conditions in cardiovascular medicine. The 2026 AHA/ACC multisocietal guideline, endorsed by ten professional societies, is the first de novo comprehensive guideline dedicated exclusively to acute PE in adults. It introduces a new five-category A-E risk classification system, a Class I recommendation for the Pulmonary Embolism Response Team (PERT), updated guidance on anticoagulation and advanced reperfusion therapies, and a structured framework for post-PE follow-up and chronic thromboembolic pulmonary hypertension (CTEPH) screening. This episode walks through all of it, using a high-risk clinical case as the backbone. Dr. Dinu Balanescu and Dr. Billy-Joe Mullinax are Co-chairs for the CardioNerds PE Series, developed in collaboration with the PERT Consortium. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Pulmonary Embolism Page CardioNerds Episode Page CardioNerds Academy Cardionerds Healy Honor Roll CardioNerds Journal Club Subscribe to The Heartbeat Newsletter! Check out CardioNerds SWAG! Become a CardioNerds Patron! Pearls: The 2026 guideline replaces “massive/submassive/low-risk” language with a new five-category A-E classification. Category A is subclinical/incidental PE; B is symptomatic with a low clinical severity score; C1-C3 stratifies intermediate-risk patients by right ventricular (RV) function and biomarkers; D1-D2 captures incipient cardiopulmonary failure (transient hypotension vs. normotensive shock with end-organ dysfunction); and E1-E2 is frank cardiopulmonary failure up to cardiac arrest. Each category carries a respiratory modifier (R) for hypoxemia, tachypnea, or need for supplemental oxygen. PERT receives a Class I recommendation. Registry data show PERT reduces time to therapeutic anticoagulation, decreases unnecessary inferior vena cava (IVC) filter use, and shortens hospital and intensive care unit (ICU) length of stay. PERT is most impactful when advanced therapy decisions are on the table. Low molecular weight heparin (LMWH) is now preferred over unfractionated heparin (UFH) for initial parenteral anticoagulation in most patients (Category C and above), given superior venous thromboembolism (VTE) recurrence reduction, predictable pharmacokinetics, no routine monitoring, and lower heparin-induced thrombocytopenia (HIT) risk. UFH is still preferred when imminent reperfusion is planned, in severe renal failure, or when rapid reversal may be needed. Categories A and B go straight to a direct oral anticoagulant (DOAC). Advanced reperfusion therapies – systemic thrombolysis, catheter-directed thrombolysis (CDT), mechanical thrombectomy (MT), and surgical embolectomy – carry Class 2B recommendations for Category D PE because available trials used surrogate endpoints only. HI-PEITHO, which showed a composite 7-day benefit for CDT plus anticoagulation vs. anticoagulation alone, was published in March 2026 after guideline lock and could not influence the current document. More trials are coming (PEERLESS 2, PE-TRACT, PERSEVERE, TORPEDO). Post-PE follow-up is now structured: outreach within 1 week of discharge, office visit with a PE-experienced clinician by 3 months, and active chronic thromboembolic pulmonary disease (CTEPD) and CTEPH screening at every visit for at least 1 year. Persistent symptoms or functional limitation beyond 3 months should trigger evaluation with a ventilation-perfusion (V/Q) scan, echocardiogram, and right heart catheterization (RHC). Notes: Notes drafted by Dr. Saahil Jumkhawala. Why did the writing committee believe a new classification system was necessary in 2026? The 2011 AHA scientific statement used “low-risk,” “submassive,” and “massive” categories – broad, imprecise, and insufficient for guiding modern management decisions. The 2019 European Society of Cardiology (ESC) guideline improved on this with low, intermediate-low, intermediate-high, and high-risk categories, but still did not capture many clinical, imaging, and laboratory variables with reliable prognostic data. The writing committee wanted a classification system that: Was more nuanced and captured the full clinical spectrum of PE severity Incorporated the clinical, laboratory, and imaging variables with the strongest outcome data Mapped directly to management decisions and could serve as a shared communication tool The result is a five-category A-E system with subcategories and a respiratory modifier, easier to memorize and use in practice. How do we apply the new five-category system at the bedside? What data points drive category assignment, and what is the significance of the respiratory modifier? Category A – Subclinical/Incidental PE Asymptomatic; PE found incidentally (e.g., on staging computed tomography (CT) for cancer) Often subsegmental; typically appropriate for outpatient management Category B – Symptomatic, Low Severity Chest pain or dyspnea, but simplified Pulmonary Embolism Severity Index (sPESI) = 0 B1: subsegmental PE; B2: non-subsegmental PE Outpatient management appropriate unless confounding comorbidity present Category C – Symptomatic, Elevated Severity Score (analogous to ESC intermediate risk) C1: normal RV size/function, normal biomarkers C2: abnormal RV function OR elevated biomarker (one of the two) C3: both abnormal RV function AND at least one elevated biomarker Respiratory modifier (R): oxygen saturation (SpO2) 30, or need for supplemental O2 Category D – Incipient Cardiopulmonary Failure D1: transient hypotension (systolic blood pressure (SBP) 90 mmHg but with end-organ dysfunction (elevated lactate, rising creatinine) Respiratory modifier (R): >6 L nasal cannula O2 or non-rebreather mask required Category E – Frank Cardiopulmonary Failure E1: recurrent or persistent hypotension with cardiogenic shock E2: refractory cardiogenic shock or cardiac arrest Respiratory modifier (R): hypoxemic or ventilatory respiratory failure Mr. Osis (our case patient): tachycardic, transient SBP 84 mmHg, lactate 3.4, requiring 3L O2 – classified as D1R. What is the evidence behind the Class I PERT recommendation, and when should PERT be involved in the context of the new triage system? PERT provides: Improved risk stratification through multidisciplinary input Expert guidance on selection and timing of advanced therapies Implementation of evidence-based protocols Education of the broader care team PERT composition varies by institution but may include: pulmonary/critical care, general cardiology, interventional cardiology, cardiac surgery, vascular surgery, hematology/oncology, emergency medicine, and pharmacy. Published data supporting Class I recommendation: Reduced time to therapeutic anticoagulation Decreased unnecessary IVC filter placement Shorter hospital and ICU length of stay Possible mortality reduction (data conflicting across registries) PERT is most impactful in Category C3 and above, particularly when advanced therapy decisions are being contemplated – though the guideline does not restrict PERT activation to any specific category threshold. What does the 2026 guideline say about initial anticoagulation choice (UFH vs. LMWH)? LMWH is the preferred initial parenteral anticoagulant for most patients with acute PE (Category C and above). Meta-analytic evidence: LMWH reduces recurrent VTE more effectively than UFH without increasing bleeding Predictable pharmacokinetics – no routine activated partial thromboplastin time (aPTT) monitoring required Lower incidence of HIT UFH is preferred when: Imminent advanced reperfusion is anticipated (systemic lysis, MT, surgical embolectomy, or extracorporeal membrane oxygenation (ECMO) cannulation) Severe renal dysfunction (unpredictable LMWH pharmacokinetics) Rapid reversibility needed Categories A and B: proceed directly to a DOAC (no parenteral bridge needed). DOACs are preferred over vitamin K antagonists (VKA) for long-term therapy in most patients, including most with cancer-associated PE. Exception: LMWH preferred for luminal gastrointestinal (GI) or genitourinary (GU) malignancies due to bleeding risk DOACs are contraindicated in pregnancy; LMWH is generally used throughout gestation and for at least 6 weeks postpartum How does the guideline navigate Category D1-D2 patients? What is the evidence base for the Class 2B recommendation for advanced therapies, and how do we choose between CDT and MT? All advanced reperfusion therapies carry a Class 2B recommendation for Category D PE: Class 2B = “may be considered” – the intervention can be used, but evidence is less certain Applies to: systemic thrombolysis, CDT, MT, and surgical embolectomy Why Class 2B? Available trials at the time of guideline finalization (early fall 2025) relied on surrogate endpoints: ULTIMA: CDT vs. anticoagulation alone – surrogate RV/LV ratio endpoint OPTALYSE: CDT dose-finding – surrogate endpoints STORM-PE: surrogate endpoints PEERLESS (New England Journal of Medicine, 2024): MT vs. CDT – included mortality, intracranial hemorrhage (ICH), major bleed, ICU admission, but was not vs. anticoagulation alone HI-PEITHO (published March 2026 at the ACC annual meeting – after guideline lock): 7-day composite of PE-related death, clinical decompensation/collapse, or PE recurrence Primary o
