468. 2026 Acute Pulmonary Embolism Guidelines with Dr. Mark Creager

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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.  

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Pearls:

  1. 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.
  2. 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.
  3. 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).
  4. 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).
  5. 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.

  1. 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.
  1. 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) <90%, respiratory rate (RR) >30, or need for supplemental O2
  • Category D – Incipient Cardiopulmonary Failure
    • D1: transient hypotension (systolic blood pressure (SBP) <90 mmHg, but responsive/self-resolving)
    • D2: normotensive shock – 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.
  1. 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.
  1. 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
  1. 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 outcome favored CDT plus anticoagulation vs. anticoagulation alone
    • Composite driven primarily by clinical decompensation/collapse
    • Could not be incorporated into current recommendations
  • Upcoming trials expected to provide hard-outcome data: PEERLESS 2, PE-TRACT, PERSEVERE, TORPEDO.
  • For Mr. Osis (post-op day 2, fresh anastomosis): systemic lysis and CDT carry high bleeding risk. MT is the most attractive option if hemodynamic deterioration progresses; anticoagulation alone with close monitoring is reasonable if he remains stable.
  1. In a Category E patient with major bleeding contraindications, how does the guideline structure the decision between systemic lysis, catheter-based therapies, surgical embolectomy, and venoarterial (VA)-ECMO?
  • Category E1 (persistent hypotension with cardiogenic shock) – four options:
    • Systemic thrombolysis: Class I in the absence of contraindications (alteplase 100 mg over 2 hours)
    • CDT: Class 2B; a bleeding-conscious alternative to systemic lysis
    • MT: Class 2A for selected E1 patients
    • Surgical pulmonary embolectomy: Class 2A for selected E1; Class 2B in Category D when lysis fails or is contraindicated; preferred when cardiac surgery resources are available, and there is obstructing right heart thrombus or patent foramen ovale (PFO) clot
  • VA-ECMO: explicitly endorsed in the 2026 guideline as a bridge to recovery, lysis-after-stabilization, MT, or surgical embolectomy in refractory cardiopulmonary collapse. Best outcomes when initiated early (pre-arrest is better than peri-arrest).
  • Reduced-dose thrombolysis (25-50 mg alteplase): considered in patients with moderate bleeding risk; possible improvement in RV function with less bleeding, though mortality benefit unproven.
  • Temporary mechanical circulatory support (MCS) – including Impella RP, ProtekDuo, and surgical right ventricular assist device (RVAD) – may bridge selected patients with refractory RV failure; data are observational and best deployed at centers with dedicated PE or shock teams.
  • For Mr. Osis (post-op day 2 with fresh anastomosis): systemic lysis and CDT are essentially contraindicated. The PERT decision favored MT on VA-ECMO, which is consistent with the 2026 guideline framework for Category E patients with major bleeding contraindications.
  1. What is the structure of post-PE follow-up, and how do we approach anticoagulation duration in a patient with cancer-associated PE?
  • Within 1 week of discharge: outreach or clinic visit (at minimum a phone call) to confirm anticoagulation adherence, assess for bleeding, and review symptoms.
  • By 3 months: in-person office visit with a PE-experienced clinician to assess symptom trajectory and determine anticoagulation duration.
    • Provoked PE with a resolved transient risk factor: 3-6 months is generally sufficient
    • Unprovoked PE or persistent risk factors: extended anticoagulation generally warranted
    • Cancer-associated PE: continue anticoagulation while cancer is active or under treatment (Class I)
  • At every visit for at least 1 year: actively screen for CTEPD/CTEPH – ask about exertional dyspnea, fatigue, and functional decline.
  • PERT or post-PE clinic models are associated with better adherence to follow-up and earlier CTEPH detection in registries.
  1. When does residual dyspnea after PE trigger a structured CTEPH workup, and what is the recommended diagnostic pathway?
  • Approximately 50% of patients have residual symptoms at 3 months post-PE.
  • After 3 months of therapeutic anticoagulation, persistent dyspnea or functional limitation triggers evaluation for CTEPD (chronic thromboembolic pulmonary disease) – this is a Class I recommendation.
  • Diagnostic pathway:
    • Echocardiogram: persistent RV dysfunction is a Class 2A indication for further evaluation
    • V/Q scan: first-line imaging for CTEPH evaluation
    • CT pulmonary angiography (CTPA): confirmatory imaging
    • RHC: required to confirm CTEPH (mean pulmonary arterial pressure (PAP) >20 mmHg with pulmonary vascular resistance (PVR) >2 Wood units (WU) on anticoagulation)
    • Cardiopulmonary exercise test (CPET): Class 2A option for patients with functional limitation but no overt pulmonary hypertension (PH) (CTEPD without H)
  • Confirmed CTEPH: refer to an expert center for pulmonary endarterectomy (PEA) candidacy assessment, balloon pulmonary angioplasty (BPA), or PH-targeted medical therapy (riociguat, treprostinil).
  • For Mr. Osis at 3 months (tricuspid annular plane systolic excursion (TAPSE) 16 mm, estimated pulmonary artery systolic pressure (PASP) 48 mmHg, exertional dyspnea): V/Q scan and RHC are indicated, with referral to a CTEPH center given high pre-test probability.
  1. Special populations: PE in pregnancy, cancer-associated PE, clot-in-transit, and IVC filters.
  • Pregnancy:
    • DOACs and warfarin are contraindicated (fetal harm, miscarriage risk)
    • LMWH is preferred throughout pregnancy and for at least 6 weeks postpartum
    • Anti-Xa monitoring is recommended in patients at weight extremes or with renal disease
    • After delivery, LMWH or warfarin can be continued; insufficient data on DOACs in breastfeeding
  • Cancer-associated PE:
    • DOACs (apixaban, edoxaban, rivaroxaban) are first-line for most patients
    • LMWH preferred for luminal GI or GU malignancies due to mucosal bleeding risk
    • Long-term management: reduced-dose apixaban (2.5 mg twice daily) or rivaroxaban after the initial treatment period may be considered
    • Continue anticoagulation while cancer is active
  • Clot-in-transit (right heart thrombus):
    • High-risk finding warranting active intervention
    • Guideline endorses mechanical or surgical thrombectomy for removal
  • IVC filters:
    • Indicated only when anticoagulation is contraindicated in the setting of acute PE
    • Use retrievable filters with a planned removal strategy
    • Routine IVC filter use is not recommended – PERT implementation has already driven down unnecessary filter use significantly

References:

  1. Creager MA, et al. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults. J Am Coll Cardiol. 2026. Available at: https://www.jacc.org/
  2. Konstantinides SV, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405. Available at: https://pubmed.ncbi.nlm.nih.gov/31504429/
  3. Jaff MR, et al. Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association. Circulation. 2011;123(16):1788-1830. doi:10.1161/CIR.0b013e318214914f. Available at: https://pubmed.ncbi.nlm.nih.gov/21422387/
  4. Piazza G, et al; HI-PEITHO Investigators. Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism. N Engl J Med. 2026. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2503980
  5. Bhatt DL, et al; PEERLESS Investigators. Mechanical Thrombectomy for Intermediate-Risk Pulmonary Embolism. N Engl J Med. 2024;391:2099-2110. doi:10.1056/NEJMoa2407772. Available at: https://pubmed.ncbi.nlm.nih.gov/39555838/
  6. Creager MA, Geary J, Barnes J. Evidence and Future Directions in Acute Pulmonary Embolism Management. J Am Coll Cardiol. 2026. Available at: https://www.jacc.org/

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