Pulmonary Embolism Archives - Cardionerds

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Pulmonary Embolism Archives - Cardionerds episodes

October 12468. 2026 Acute Pulmonary Embolism Guidelines with Dr. Mark Creager
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.
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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) <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.
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 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.
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.
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.
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.
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:
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/
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/
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/
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
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/
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/
45 min
July 10458. The Golden Age of Pulmonary Embolism Randomized Controlled Trials with Dr. Jay Giri
CardioNerds co-chairs Dr. Dinu Balanescu and Dr. Billy Joe Mullinax, along with FIT lead Dr. Shiavax Rao, discuss the evolving landscape of randomized controlled trials in pulmonary embolism with Dr. Jay Giri, interventional cardiologist, Associate Professor of Medicine, and Director of the Cardiovascular Catheterization Laboratories at the Hospital of the University of Pennsylvania. This episode examines the historical evidence behind systemic thrombolysis, the emergence of catheter-directed therapies and mechanical thrombectomy, and the landmark RCTs – STORM-PE, PEERLESS, HI-PEITHO, and PEERLESS II – that are reshaping intermediate-risk PE management. The discussion highlights challenges in PE trial design, the critical importance of clinical deterioration as an endpoint, and why this era represents an unprecedented wave of evidence generation in PE. Audio editing for this episode was performed by CardioNerds Intern, Dr. Julia Marques Fernandes.
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:
Systemic thrombolysis in intermediate-risk PE reduces hemodynamic decompensation but at the cost of ~1.5–2% intracranial hemorrhage risk – a near-zero net benefit that has driven the search for safer catheter-based alternatives.
“Focus on clinical deterioration, not mortality” – Due to crossover design in contemporary PE RCTs, control-arm patients who decompensate are rescued with advanced therapies, biasing mortality toward the null. Clinical deterioration is the most informative endpoint to watch in HI-PEITHO, PRAGUE-26, and PEERLESS II.
HI-PEITHO is the first large RCT to demonstrate that catheter-directed fibrinolysis plus anticoagulation significantly reduces the composite of PE-related death, cardiorespiratory decompensation, or PE recurrence versus anticoagulation alone (RR 0.39; 95% CI 0.20–0.77; P=0.005), with no intracranial hemorrhage in either arm.
The four major upcoming/recently reported PE RCTs (HI-PEITHO, PRAGUE-26, PEERLESS II, PE-TRACT) enroll progressively different risk populations – from the most enriched (HI-PEITHO) to the most permissive (PE-TRACT, which includes intermediate-low risk patients) – enabling a nuanced understanding of which patients benefit most from intervention.
PE device clearance follows a fundamentally different FDA pathway than structural heart devices (single-arm safety/efficacy studies vs. mandated RCTs), yet market forces and clinical need have ultimately driven industry and government to sponsor large-scale RCTs – a lesson in how evidence development can evolve organically alongside regulatory frameworks.
Notes:
Notes drafted by Dr. Shiavax Rao.
Question #1: What is the current evidence behind advanced PE therapies?
Systemic thrombolysis: Sixteen RCTs over 40 years (1972–2014) enrolling nearly 2,000 patients have studied systemic thrombolysis in intermediate-risk PE. The landmark PEITHO trial (n=1,006) showed that tenecteplase reduced the composite of death or hemodynamic collapse (2.6% vs. 5.6%; P=0.015), driven primarily by reduced hemodynamic decompensation (1.6% vs. 5.0%; P=0.002). However, this came at the cost of increased major bleeding (6.3% vs. 1.5%; P<0.001) and a ~2% rate of intracranial hemorrhage. Meta-analyses of systemic thrombolysis trials show a small absolute mortality benefit (~1–2%) that is closely offset by bleeding risk, explaining why guidelines have not broadly recommended systemic thrombolysis for intermediate-risk PE.
Catheter-directed thrombolysis (CDT): The ULTIMA trial (n=59) was the first RCT of ultrasound-assisted CDT (EkoSonic/EKOS system) vs. anticoagulation alone in intermediate-risk PE. CDT showed superior RV/LV ratio improvement at 24 hours (decrease of 0.30 ± 0.20 vs. 0.03 ± 0.16; P<0.001), but this difference was no longer significant at 90 days. The CANARY trial, initiated in Iran in 2019, was halted prematurely due to the COVID-19 pandemic but largely verified ULTIMA’s findings, with a signal that RV benefits may persist at 90 days.
Mechanical thrombectomy – single-arm data: The FLARE trial demonstrated a 25% reduction in RV/LV ratio at 48 hours with large-bore aspiration thrombectomy (FlowTriever). The EXTRACT-PE trial showed significant RV/LV ratio reduction with the Indigo aspiration system with a low major adverse event rate. The FLASH registry (FlowTriever) reported a mean 7.6 mmHg drop in mean PA pressure and RV/LV ratio decrease from 1.23 to 0.98 at 48 hours.
STORM-PE (2025): The first RCT of mechanical thrombectomy (computer-assisted vacuum thrombectomy [CAVT] with the Indigo/Penumbra system) vs. anticoagulation alone. One hundred patients were randomized across 22 sites. CAVT was superior for the primary endpoint of 48-hour RV/LV ratio reduction (0.52 vs. 0.24; difference 0.27; P<0.001), with earlier normalization of vital signs and comparable major adverse event rates (4.3% vs. 7.5%; P=0.681). Two PE-related deaths occurred in the CAVT arm. The trial was not powered for mortality or longer-term outcomes.
PEERLESS (2025): The first RCT comparing two interventional strategies head-to-head – large-bore mechanical thrombectomy (FlowTriever) vs. CDT – in 550 patients with intermediate-risk PE. The primary hierarchical win ratio composite favored LBMT (win ratio 5.01; 95% CI 3.68–6.97; P<0.001), driven primarily by fewer clinical deterioration/bailout events (1.8% vs. 5.4%; P=0.04) and substantially less post-procedural ICU use (41.6% vs. 98.6% admission rates). No significant differences in mortality, intracranial hemorrhage, or major bleeding were observed. RV/LV ratio reduction was similar between arms. LBMT was associated with shorter hospital stays and fewer 30-day readmissions.
Question #2: What are the challenges with conducting RCTs in PE?
Crossover and rescue therapy: Unlike early TAVR trials where control-arm patients could not cross over to the device arm, contemporary PE trials allow crossover upon clinical deterioration. This is ethically necessary given available therapies but biases mortality toward the null, making it unlikely that any individual trial – or even a meta-analysis of the four major trials (~2,400–3,000 patients combined) – will demonstrate a mortality difference.
Heterogeneity of intermediate-risk PE: Two patients meeting ESC intermediate-high risk criteria (RV dysfunction + elevated troponin) can look clinically very different – one may be tachypneic on 5 liters of oxygen, while another is comfortable on room air. This heterogeneity complicates enrollment, endpoint detection, and generalizability.
Endpoint selection: Early PE trials relied on surrogate imaging endpoints (RV/LV ratio, PA pressure reduction, Miller score). While these demonstrate proof-of-concept, they have not moved guidelines. Clinically relevant endpoints – mortality, clinical deterioration, functional status, quality of life – are needed but require larger sample sizes and longer follow-up.
Funding and maturation of the field: Trials require buy-in from government or industry funders. It took time for the field to mature enough to estimate effect sizes for trial powering, accumulate sufficient operator experience to ensure internal validity, and for industry to recognize that market adoption required randomized evidence despite existing FDA clearance.
FDA regulatory pathway: PE devices are cleared via a 510(k) pathway requiring single-arm studies (~100–150 patients) demonstrating safety and RV/LV ratio improvement – a much lower bar than the pre-market approval pathway requiring RCTs mandated for structural heart devices (e.g., TAVR, MitraClip). While this has enabled rapid innovation and market competition, it initially reduced the incentive for industry-sponsored RCTs.
Question #3: What are the upcoming/recently reported RCT trials in PE?
HI-PEITHO (published 2026, NEJM): Multinational adaptive-design RCT of ultrasound-facilitated CDT (EkoSonic system, alteplase 2 mg bolus + 1 mg/hr/catheter × 7 hours) plus anticoagulation vs. anticoagulation alone in 544 patients with enriched intermediate-high risk PE (RV/LV ≥1.0, elevated troponin, plus ≥2 of: SBP ≤110, HR ≥100, RR >20). Primary composite of PE-related death, cardiorespiratory decompensation/collapse, or symptomatic PE recurrence within 7 days: 4.0% intervention vs. 10.3% control (RR 0.39; 95% CI 0.20–0.77; P=0.005). Effect driven by reduced cardiorespiratory decompensation. Major bleeding at 7 days: 4.1% vs. 2.2% (P=0.32). No intracranial hemorrhage in either arm. Clinical deterioration measured using the National Early Warning Score (NEWS), a validated ordinal scoring system incorporating vital signs – more sensitive at detecting decompensation than binary clinical criteria.
PRAGUE-26: Czech Republic government-sponsored RCT with a design essentially identical to HI-PEITHO in terms of sample size and primary endpoint, but using standard (non-ultrasound-assisted) CDT catheters in the interventional arm. Enrolling well; results anticipated in the near term.
PEERLESS II: Industry-sponsored (Inari/Boston Scientific) RCT of large-bore mechanical thrombectomy (FlowTriever) plus anticoagulation vs. anticoagulation alone in up to 1,200 patients with enriched intermediate-high risk PE (enrichment criteria slightly less stringent than HI-PEITHO). Five-component hierarchical primary endpoint assessed via win ratio: (1) mortality, (2) clinical deterioration (defined by binary clinical criteria – pressor initiation, SBP <90 for sustained period, mechanical circulatory support, or significant respiratory decompensation/intubation – a less sensitive measure than NEWS), (3) recurrent PE admission, (4) non-deterioration-based bailout crossover at day 3, and (5) 48-hour dyspnea score. The larger sample size compensates for the less sensitive clinical deterioration definition.
PE-TRACT: NIH-sponsored, open-label, assessor-blinded RCT of CDT (any FDA-cleared device – CDT or mechanical thrombectomy, strategy trial) plus anticoagulation vs. anticoagulation alone in 500 patients with intermediate-risk PE (most permissive enrollment – includes intermediate-low risk patients). Co-primary endpoints at 3 months (peak VO₂ on cardiopulmonary exercise testing) and 12 months (NYHA functional class), analyzed sequentially. Designed to answer the longer-term functional question rather than early clinical deterioration.
Question #4: What does the future of PE research look like?
Unprecedented evidence generation: Across STORM-PE, PEERLESS, HI-PEITHO, PEERLESS II, PE-TRACT, PRAGUE-26, PEITHO-3, and high-risk PE trials (PERSEVERE, TORPEDO-NL), approximately 8–9 RCTs are enrolling or recently completed – an unparalleled volume of comparative evidence in any cardiovascular subspecialty over such a short period.
Guideline impact: The 2026 AHA/ACC PE Guideline already reflects the evolving evidence landscape, with Class 2a–2b recommendations for CDT and MT in select PE categories. Results from HI-PEITHO, PEERLESS II, PRAGUE-26, and PE-TRACT have the potential to substantially strengthen these recommendations, particularly if clinical deterioration endpoints are positive.
PERT evolution: As evidence clarifies which patients benefit from intervention, PERT programs may transition from primarily clinical decision-making bodies to systems-of-care delivery engines – analogous to STEMI systems – focused on efficient, protocol-driven care and real-world evidence generation for quality improvement.
Innovation ecosystem: The relatively permissive FDA clearance pathway has fostered a competitive device landscape with multiple manufacturers and device types, contrasting with the prolonged duopoly in the TAVR space. This competition may drive technological improvement and more favorable economics.
Caution with real-world evidence: While real-world evidence is valuable for quality improvement and systems-of-care assessment, it should be used cautiously for comparative effectiveness analyses due to irreconcilable confounding and limitations in causal inference. RCTs remain the gold standard for comparative questions.
References:
★ Rosenfield K, Klok FA, Piazza G, et al. Ultrasound-facilitated, catheter-directed fibrinolysis for acute pulmonary embolism. N Engl J Med. 2026;394(22):2131-2141. doi:10.1056/NEJMoa2503539
★ Lookstein RA, Konstantinides SV, Weinberg I, et al. Randomized controlled trial of mechanical thrombectomy with anticoagulation versus anticoagulation alone for acute intermediate-high risk pulmonary embolism: primary outcomes from the STORM-PE trial. Circulation. 2026;153(1):21-34. doi:10.1161/CIRCULATIONAHA.125.077232
★ Jaber WA, Gonsalves CF, Stortecky S, et al. Large-bore mechanical thrombectomy versus catheter-directed thrombolysis in the management of intermediate-risk pulmonary embolism: primary results of the PEERLESS randomized controlled trial. Circulation. 2025;151(5):260-273. doi:10.1161/CIRCULATIONAHA.124.072364
★ Gonsalves CF, Gibson CM, Stortecky S, et al. Randomized controlled trial of mechanical thrombectomy vs catheter-directed thrombolysis for acute hemodynamically stable pulmonary embolism: rationale and design of the PEERLESS study. Am Heart J. 2023;266:128-137. doi:10.1016/j.ahj.2023.09.002
★ Sista AK, Troxel AB, Tarpey T, et al. Rationale and design of the PE-TRACT trial: a multicenter randomized trial to evaluate catheter-directed therapy for the treatment of intermediate-risk pulmonary embolism. Am Heart J. 2025;281:112-122. doi:10.1016/j.ahj.2024.11.016
★ Giri J, Sista AK, Weinberg I, et al. Interventional therapies for acute pulmonary embolism: current status and principles for the development of novel evidence: a scientific statement from the American Heart Association. Circulation. 2019;140(20):e774-e801. doi:10.1161/CIR.0000000000000707
★ Zhang RS, Maqsood MH, Sharp ASP, et al. Efficacy and safety of anticoagulation, catheter-directed thrombolysis, or systemic thrombolysis in acute pulmonary embolism. JACC Cardiovasc Interv. 2023;16(22):2781-2793. doi:10.1016/j.jcin.2023.09.014

Additional References
Rosovsky RP, Konstantinides SV, Moriarty JM, et al. A prospective, multicenter, randomized controlled trial evaluating anticoagulation alone vs anticoagulation plus computer assisted vacuum thrombectomy for the treatment of intermediate-high-risk acute pulmonary embolism: rationale and design of the STORM-PE study. Am Heart J. 2025;288:1-14. doi:10.1016/j.ahj.2025.03.018
Klok FA, Piazza G, Sharp ASP, et al. Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: rationale and design of the HI-PEITHO study. Am Heart J. 2022;251:43-53. doi:10.1016/j.ahj.2022.05.011
Creager MA, Barnes GD, Giri J, 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;87(7):e77-e206. doi:10.1016/j.jacc.2025.11.027
Piazza G. Advanced management of intermediate- and high-risk pulmonary embolism: JACC focus seminar. J Am Coll Cardiol. 2020;76(18):2117-2127. doi:10.1016/j.jacc.2020.05.028
Zuo Z, Yue J, Dong BR, et al. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2021;4(4):CD004437. doi:10.1002/14651858.CD004437.pub6
Kroupa J, Buk M, Weichet J, et al. A pilot randomised trial of catheter-directed thrombolysis or standard anticoagulation for patients with intermediate-high risk acute pulmonary embolism (CANARY). EuroIntervention. 2022;18(8):e657-e665. doi:10.4244/EIJ-D-22-00194
Zuin M, Lang I, Chopard R, et al. Innovation in catheter-directed therapy for intermediate-high-risk and high-risk pulmonary embolism. JACC Cardiovasc Interv. 2024;17(20):2390-2408. doi:10.1016/j.jcin.2024.07.037
Harvey JJ, Huang S, Uberoi R. Catheter-directed therapies for the treatment of high risk (massive) and intermediate risk (submassive) acute pulmonary embolism. Cochrane Database Syst Rev. 2022;8(8):CD013083. doi:10.1002/14651858.CD013083.pub2
Kim JM, Horbal SR, Mewaldt C, et al. Mechanical thrombectomy and catheter-directed thrombolysis in acute pulmonary embolism: trends and practice patterns in the PERT Consortium Registry (2016-2024). J Am Coll Cardiol. 2026;87(13):1271-1283. doi:10.1016/j.jacc.2025.12.044
Planer D, Yanko S, Matok I, et al. Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis. CMAJ. 2023;195(24):E833-E843. doi:10.1503/cmaj.221655
Farmakis IT, Binder H, Chopard R, et al. Reperfusion strategies for acute pulmonary embolism: design and rationale of RECONNECT-PE – a living systematic review and meta-analysis. Am Heart J. 2026;295:107365. doi:10.1016/j.ahj.2026.107365
Rashedi S, Leyva H, Hamade N, et al. Fibrinolytic therapy for thromboembolic diseases: approved indications and future directions. J Am Coll Cardiol. 2025;86(14):1395-1416. doi:10.1016/j.jacc.2025.07.048
Creager MA, Barnes GD, Giri J. A field in transition: catheter-based therapy in the 2026 AHA/ACC acute pulmonary embolism guideline. J Am Coll Cardiol. 2026;87(13):1284-1288. doi:10.1016/j.jacc.2026.01.024
30 min
June 21455. The Long-Term Management Of Patients With Pulmonary Embolism with Dr. Soophia Naydenov
CardioNerds (Amit and Dan), Billy Joe Mullinax, and Saahil Jumkhawala discuss the long term management of pulmonary embolism with Dr. Soophia Naydenov. The episode focuses on the approach to patients who struggle with persistent symptoms like dyspnea and fatigue even after completing the acute phase of anticoagulation. This spectrum of disease, ranging from mild post-PE impairment to chronic thromboembolic pulmonary hypertension (CTEPH), requires a structured follow-up. The discussion covers the critical importance of identifying CTEPH early, the necessary timelines for follow-up, and the appropriate objective screening tools and invasive testing to guide patient care toward full functional recovery. Audio editing by CardioNerds academy intern, Grace Qiu.
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.
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Acronyms
PE: Pulmonary Embolism
PERT: Pulmonary Embolism Response Team
CTEPH: Chronic Thromboembolic Pulmonary Hypertension
QL: Quality of Life
VTE: Venous Thromboembolism
DASH: D-dimer, Age, Sex, History of non-provoked PE (a risk score)
CPET: Cardiopulmonary Exercise Testing
PFTs: Pulmonary Function Tests
VQ Scan: Ventilation-Perfusion Scan
DOACs: Direct Oral Anticoagulants
TPA: Tissue Plasminogen Activator (Thrombolytics)
ECMO: Extracorporeal Membrane Oxygenation
Pearls:
Post-PE “Syndrome” is a Spectrum: It is more accurately a spectrum of disease (sequelae of PE) rather than a single syndrome, ranging from mild fatigue/dyspnea to the most severe form, CTEPH.
Structured Follow-up is Mandatory: All PE survivors need a structured follow-up, typically with checkpoints at 3, 6, 12, and 16–24 months, with the primary goal being to detect CTEPH, the deadliest, yet potentially curable, disease on the spectrum.
Screening Should Be Objective and Practical: When screening for persistent symptoms, use objective assessment tools like the Post-VTE Functional Status (PVFS) scale or the Modified Medical Research Council (MMR-C) scale, as highly comprehensive but cumbersome tools (like the PE Quality of Life questionnaire) may not be practical for routine clinical use. Recurrence Risk Scores Aid in Anticoagulation Duration: Simple scores like the DASH score or the HERDO2 score (for women) can provide guidance when considering the continuation versus discontinuation of anticoagulation after the initial treatment phase.
Invasive Testing for Persistent Symptoms: If a patient remains symptomatic at the 6-month mark despite normal non-invasive testing (chest X-ray, ECG, PFTs, six-minute walk, echo, VQ scan, CPET), consider invasive testing such as Right Heart Catheterization (RHC) at rest or with exercise, or an invasive CPET.
Notes:
Notes drafted by Saahil Jumkhawala.
1. The Spectrum of Post-PE Disease
The term “post-PE syndrome” should be used with caution, as it refers to a spectrum of disease rather than a single entity.
This spectrum includes symptoms (sequelae) that exist in a patient’s life following an incidental PE event that they did not have before.
On one extreme is Chronic Thromboembolic Pulmonary Hypertension (CTEPH):
The definition is clear, but it is the most deadly type, though thankfully rare (2% to 4%).
It involves a residual clot and pulmonary hypertension identifiable at rest.
In the middle is Chronic Thromboembolic Disease (CTED):
Patients may have residual defects seen on a VQ or CT scan, but they do not have pulmonary hypertension.
On the other side is a milder disease, which can include fatigue, dyspnea, or a patient’s perceived impairment, where the definitions of CTEPH and CTED are not met, but the patient remains symptomatic.
2. Structured Follow-up and Screening for Post-PE Symptoms
Structured follow-up is key for all PE survivors, though the structure may vary based on available resources (PCP, Cardiology, Pulmonary, or multidisciplinary clinic).
Recommended Timeline for Follow-up: Data from studies like ELOPE and FOCUS suggest checkpoints at 3, 6, 12, and up to 16 to 24 months.
This timeline is designed to identify patients who may develop CTEPH.
88% of patients who develop CTEPH will be identified within about a year.
A structured follow-up can reduce the delay in CTEPH diagnosis from 10–12 months to 4–6 months.
Personal Practice Note: A quick 2–3 week/30-day check-in is recommended for severely ill patients (e.g., those who had TPA, profound shock, or ECMO support) to ensure medication compliance, manage symptoms, and identify red flags.
Screening Tools (Objective Assessment):
The first step is an inventory of patient symptoms, leaning toward objective rather than subjective assessment.
Recommended Simple Tools:
Modified Medical Research Council (MMR-C) for dyspnea evaluation.
Post-VTE Functional Status (PVFS) scale.
The Pulmonary Embolism Quality of Life (QL) questionnaire is comprehensive but long, making it tedious and better suited for research.
Future Utility: Technology (AI/electronic tools) may assist in administering these questionnaires before the clinic visit, presenting the information as a “dashboard” for the provider.
3. Management of Persistent Symptoms and Further Testing
Initial Non-Invasive Tests (Often done at 3 months):
Echocardiogram
VQ Scan
Full PFTs
Six-minute walk
CPET
Further Evaluation for Persistent Symptoms (e.g., at 6 months): If non-invasive tests (Chest X-ray, ECG, CPET) are normal but symptoms persist, more invasive testing should be considered as the patient has not returned to baseline.
Repeat VQ scan or echocardiogram if symptoms have changed.
Right Heart Catheterization (RHC) at rest or with exercise.
Invasive CPET.
PA gram (Pulmonary Angiogram) to assess vasculature.
4. Recurrence Risk and Anticoagulation Duration
The decision to continue or discontinue anticoagulation depends on the patient’s risk factors, the situation of the PE (provoked or unprovoked), presence of active cancer, and patient preference.
Recurrence Risk Scores:
Simple scores are preferred for practicality.
DASH Score.
HERDO2 Score (particularly for women).
The Vienna Score can be considered if the question is whether to restart anticoagulation after a disruption.
Role of D-dimer in Abbreviation: While D-dimer can be used to guide the decision to restart anticoagulation after a planned pause (if D-dimer is high, resume), patient symptoms are preferable to guide management decisions like early abbreviation.
5. Prevention of Post-PE Syndrome
Currently, there is no clear tool known to prevent the post-PE syndrome/spectrum of disease.
Best Current Advice for Prevention/Recovery:
Anticoagulation compliance.
Pulmonary rehabilitation, which aids in faster recovery.
General precautions, such as smoking cessation and body weight management.
Future Research: Ongoing trials are investigating whether acute management strategies (e.g., using thrombolytics in intermediate-risk PE) can prevent long-term sequelae. (The PYTHO trial did not show a reduced rate of CTEPH in intermediate-risk PE patients who received thrombolytics).
References:
Khan, F., Tritschler, T., Kahn, S. R., & Rodger, M. A. “Venous Thromboembolism.” The Lancet, vol. 398, no. 10294, 2021, pp. 64-77. doi:10.1016/S0140-6736(20)32658-1.
Kearon, C., & Kahn, S. R. “Long-Term Treatment of Venous Thromboembolism.” Blood, vol. 135, no. 5, 2020, pp. 317-325. doi:10.1182/blood.2019002364.
Kahn, S. R., & de Wit, K. “Pulmonary Embolism.” The New England Journal of Medicine, vol. 387, no. 1, 2022, pp. 45-57. doi:10.1056/NEJMcp2116489.
Di Nisio, M., van Es, N., & Büller, H. R. “Deep Vein Thrombosis and Pulmonary Embolism.” The Lancet, vol. 388, no. 10063, 2016, pp. 3060-3073. doi:10.1016/S0140-6736(16)30514-1.
Chopard, R., Albertsen, I. E., & Piazza, G. “Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review.” JAMA, vol. 324, no. 17, 2020, pp. 1765-1776. doi:10.1001/jama.2020.17272.
20 min
June 01452. Risk stratification in Acute Pulmonary Embolism with Dr. Stavros Konstantinides
CardioNerds (Dr. Billy-Joe Mullinax, Dr. Dinu Balanescu, and Dr. Jane Ehret) discuss risk stratification in acute pulmonary embolism with Dr. Stavros Konstantinides, Chair of the 2019 ESC Pulmonary Embolism Guidelines. Using a real-world case, this episode explores how modern PE care has moved beyond “massive” and “submassive” labels toward a dynamic, physiology-based approach. The discussion highlights the limitations of static risk scores, the importance of right ventricular dysfunction and biomarkers, and why normotension does not imply stability. Special emphasis is placed on intermediate-high risk PE, early identification of impending hemodynamic collapse, and the role of lactate, serial reassessment, and PERT teams in guiding escalation of care. Audio editing by CardioNerds intern, Joshua Khorsandi.
The 2026 American multi-society PE guidelines were published after this episode was recorded.
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
Stable blood pressure does not mean low risk in PE
Hypotension is a late finding. Patients may have severe RV failure, hypoxia, and tissue hypoperfusion while remaining normotensive — a key concept behind “normotensive shock.”
Risk stratification in PE must be dynamic, not static
Legacy scores like PESI and Bova provide a snapshot and predict 30-day mortality, but they do not capture short-term trajectory or impending hemodynamic collapse.
Intermediate-high risk PE is a dangerous and heterogeneous group
Patients with RV dysfunction, positive biomarkers, tachycardia, hypoxemia, and elevated lactate may have in-hospital mortality approaching 15%, rivaling STEMI.
Lactate is a critical but underutilized marker in PE
Elevated lactate reflects tissue hypoxia and early circulatory failure and may identify patients at risk for collapse before blood pressure declines.
PERT enables physiology-driven, patient-centered PE care
PERT teams operationalize continuous reassessment, integrate imaging, labs, and clinical trajectory, and allow timely escalation — shifting PE management from rigid categories to real-time decision-making.
Notes
Drafted by Dr. Jane Ehret.
1. What is the contemporary framework for risk stratification in acute pulmonary embolism?
Modern PE risk stratification prioritizes hemodynamics and right ventricular (RV) function rather than clot burden.
The 2019 ESC Guidelines classify PE into high risk, intermediate risk (low vs high), and low risk, based on: Hemodynamic status, RV dysfunction on imaging, and Cardiac biomarkers.
This framework emphasizes early mortality risk but requires clinical context to guide escalation decisions.
2. Why is normotension insufficient to define “stability” in PE?
Blood pressure is a late marker of circulatory failure in PE.
Patients can maintain normal BP through Tachycardia, Increased sympathetic tone, and RV compensation.
Many patients with preserved BP may already have shock physiology, including hypoxemia, elevated lactate, and RV failure — sometimes referred to as “normotensive shock.”
3. How should intermediate-risk PE be conceptualized clinically?
Intermediate-risk PE is heterogeneous, ranging from patients who do well on anticoagulation to those who deteriorate rapidly.
Intermediate-high risk PE is defined by RV dysfunction on imaging and positive cardiac biomarkers.
Clinical features such as tachycardia, increasing oxygen requirement, and elevated lactate identify patients at highest risk within this group.
4. What are the strengths and limitations of commonly used PE risk scores?
Legacy scores are useful for initial risk categorization but are static and limited in predicting short-term deterioration.
Most scores were developed to predict mortality or complications at fixed time points rather than dynamic clinical trajectory.
5. What are the commonly used risk scores and clinical tools in PE, and what is each designed to predict?
ESC Risk Stratification Algorithm: Identifies high-risk PE by hemodynamics. Uses PESI or sPESI in normotensive patients to distinguish low-risk from non–low-risk PE. Uses RV dysfunction and biomarkers to differentiate intermediate-low from intermediate-high risk. Forms the basis of many institutional PE pathways.
PESI and sPESI: Validated to predict 30-day mortality. Widely used to identify low-risk patients appropriate for outpatient management. Heavily influenced by age and comorbidities.
Bova Score: Predicts 30-day PE-related complications in normotensive patients.
Composite PE Shock Score (CPES): Predicts normotensive shock in hemodynamically stable PE patients.
Pulmonary Embolism Progression (PEP) Score: Predicts progression from intermediate-risk to high-risk PE within 72 hours of diagnosis.
PE Short-term Clinical Outcomes Risk Estimation (PE-SCORE): Predicts clinical deterioration or death within 5 days of PE diagnosis.
Hestia Criteria: Identifies low-risk PE patients safe for outpatient treatment.
Wells’ Criteria and Revised Geneva Score: Determine pretest probability for diagnostic triage.
PERC Score: Rules out PE in very low-risk patients.
6. What is the role of biomarkers in PE risk stratification?
Troponin and natriuretic peptides reflect RV myocardial injury and strain.
Current guidelines treat biomarkers as binary (positive vs negative), despite risk being continuous.
Biomarkers are most helpful for: Initial risk classification.
They are less useful for: Short-interval monitoring and Detecting rapid clinical deterioration.
7. Why is lactate an important physiologic marker in PE?
Lactate reflects global tissue hypoxia and impaired perfusion.
Elevated lactate may identify patients with: Early circulatory failure and Increased risk of imminent hemodynamic collapse.
Lactate is not currently included in ESC risk algorithms but may add important prognostic information in intermediate-risk patients.
8. How does trajectory influence decision-making in PE management?
Risk stratification should be viewed as a dynamic process, not a one-time label.
Worsening clinical trajectory may include: Rising heart rate, Increasing oxygen needs, Rising lactate, and Progressive RV dysfunction.
Serial reassessment is essential for timely escalation of care.
9. What role do Pulmonary Embolism Response Teams (PERT) play in risk stratification?
PERT facilitates: Multidisciplinary decision-making and Integration of imaging, biomarkers, and clinical physiology.
PERT is most valuable for: Intermediate-risk and high-risk PE and Patients with complex comorbidities or uncertain trajectory.
PERT enables a shift from category-based to physiology-driven PE care.
References
1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J. 2019;54(3):1901647. Published 2019 Oct 9. doi:10.1183/13993003.01647-2019
2. Leidi A, Bex S, Righini M, Berner A, Grosgurin O, Marti C. Risk Stratification in Patients with Acute Pulmonary Embolism: Current Evidence and Perspectives. J Clin Med. 2022;11(9):2533. Published 2022 Apr 30. doi:10.3390/jcm11092533
3. Choi WH, Kwon SU, Jwa YJ, et al. The pulmonary embolism severity index in predicting the prognosis of patients with pulmonary embolism. Korean J Intern Med. 2009;24(2):123-127. doi:10.3904/kjim.2009.24.2.123
4. Jiménez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15):1383-1389. doi:10.1001/archinternmed.2010.199
5. Chen X, Shao X, Zhang Y, et al. Assessment of the Bova score for risk stratification of acute normotensive pulmonary embolism: A systematic review and meta-analysis. Thromb Res. 2020;193:99-106. doi:10.1016/j.thromres.2020.05.047
6. Zhang RS, Yuriditsky E, Zhang P, et al. Composite Pulmonary Embolism Shock Score and Risk of Adverse Outcomes in Patients With Pulmonary Embolism. Circ Cardiovasc Interv. 2024;17(8):e014088. doi:10.1161/CIRCINTERVENTIONS.124.014088
7. Zhang RS, Alam U, Sharp ASP, et al. Validating the Composite Pulmonary Embolism Shock Score for Predicting Normotensive Shock in Intermediate-Risk Pulmonary Embolism. Circ Cardiovasc Interv. 2024;17(2):e013399. doi:10.1161/CIRCINTERVENTIONS.123.013399
8. Ehret J, Wakefield D, Badlam J, Antkowiak M, Erdreich B. Development of the Pulmonary Embolism Progression (PEP) score for predicting short-term clinical deterioration in intermediate-risk pulmonary embolism: a single-center retrospective study. J Thromb Thrombolysis. 2025;58(2):243-253. doi:10.1007/s11239-024-03051-5
9. Weekes AJ, Raper JD, Lupez K, et al. Development and validation of a prognostic tool: Pulmonary embolism short-term clinical outcomes risk estimation (PE-SCORE). PLoS One. 2021;16(11):e0260036. Published 2021 Nov 18. doi:10.1371/journal.pone.0260036
10. Zondag W, Hiddinga BI, Crobach MJ, et al. Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism. Eur Respir J. 2013;41(3):588-592. doi:10.1183/09031936.00030412
11. Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001;135(2):98-107. doi:10.7326/0003-4819-135-2-200107170-00010
12. Wolf SJ, McCubbin TR, Feldhaus KM, Faragher JP, Adcock DM. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med. 2004;44(5):503-510. doi:10.1016/j.annemergmed.2004.04.002
13. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144(3):165-171. doi:10.7326/0003-4819-144-3-200602070-00004
14. Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2(8):1247-1255. doi:10.1111/j.1538-7836.2004.00790.x
15. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6(5):772-780. doi:10.1111/j.1538-7836.2008.02944.x
26 min
April 24447. Pulmonary Embolism: Approach to Systemic Thrombolysis in Acute Pulmonary Embolism with Dr. Allison Burnett
CardioNerds Drs. Dinu Balanescu, Billy-Joe Mullinax, and Mariana Garcia discuss systemic thrombolysis in pulmonary embolism with expert Dr. Allison Burnett. Audio editing by CardioNerds Academy intern, student doctor, Pace Wetstein.
Pulmonary embolism is the third leading cause of cardiovascular death in the US, and high-risk PE carries a 30-day mortality risk as high as 30-50%. In this episode, we discuss the indications for systemic thrombolysis, including high-risk PE and cardiac arrest. We addressed how to appropriately select candidates for systemic thrombolysis, balancing the high risk of bleeding. Additionally, we discussed anticoagulation management and timing concurrent with lytic therapy, as well as the importance of multidisciplinary PERT teams.
The 2026 American multi-society PE guidelines were published after this episode was recorded.
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
Risk stratification is crucial in acute pulmonary embolism care. Based on the ESC 2019 guidelines, low-risk PE patients are those who are normotensive with no evidence of right ventricular dysfunction. Intermediate risk includes two categories: intermediate-low, with normotensive patients who have a high PE score with negative biomarkers, and intermediate-high risk, which has elevated biomarkers or signs of RV strain. High-risk PE includes hemodynamically unstable patients (SBP<90) who have end-organ dysfunction, shock, or cardiac arrest.
The 2026 American multi-society PE guidelines presented a new clinical classification scheme is presented, entitled “Acute Pulmonary Embolism Clinical Categories,” with 5 categories (A-E) and subcategories, ranging from low to high risk for adverse outcomes.
Systemic lysis has been studied in patients at high and intermediate risk. Overall, the reduction in mortality has been seen in patients with high-risk PE.
Systemic thrombolysis is associated with high rates of bleeding, 2% fatal or high-risk intracranial hemorrhage per the PEITHO trial; therefore, selecting the appropriate population is critical to improve outcomes and balance the risks and benefits.
Multidisciplinary PERT teams are crucial for making high-quality decisions, and stewardship is necessary to optimize the care of patients with PE.
Notes
Notes: Notes drafted by Dr. Mariana Garcia-Arango
What is the role of systemic thrombolysis in the current era of available catheter-directed therapies?
Thrombolytic therapy reduces mortality, PE recurrence, and PE-related mortality in patients with acute PE.
The evidence supports use during high-risk PE and cardiac arrest.
The clinical presentation is often severe, with high stakes and limited time to mobilize to the cath lab on time for catheter therapies, especially in rural populations.
How to approach the use of systemic thrombolysis during CPR?
Cardiac arrest from PE carries a very poor outlook, with survival rates under 10%. Rapid, targeted interventions to restore circulation are critical.
Systemic thrombolysis may be considered for patients in cardiac arrest due to confirmed or strongly suspected pulmonary embolism, especially when standard ACLS interventions have not been successful.
What is the best anticoagulation approach while using lytics?
Most of the time, we should opt for low-molecular-weight heparin over unfractionated heparin, which has been shown to lead to less major bleeding and reduction of recurrent PE.
Exceptions to the rule include renal dysfunction or if there is consideration of cannulation for ECMO or other invasive procedures.
There is variation in practice regarding timing and initiation of anticoagulation while using lytics. There are different protocols given the variety of how studies were conducted.
If they are going to get mechanical catheter-based therapy, the trend is to prefer LMWH.
When lytics are included, either systemic or catheter-directed lytics, there is flexibility and room to discuss with the multidisciplinary PERT team which strategy to use.
Future studies and trials are needed to standardize the best therapies.
What are the pharmacologic properties of available thrombolytics?
Thrombolytics catalyze the conversion of plasminogen to plasmin, leading to fibrin degradation and thrombus dissolution.
Alteplase is a recombinant tissue plasminogen activator, administered intravenously at a dose of IV 100 mg infusion over 2 hours. In cardiac arrest, the initial: 50 mg bolus over 2 minutes and continue CPR; after 15 minutes, if return of spontaneous circulation is not achieved and the medical team decides to continue CPR, repeat 50 mg bolus.
Tenecteplase is a modified variant of alteplase with increased fibrin specificity. The usual dose is weight-based and delivered via IV bolus, which facilitates rapid delivery in emergency settings. Dose per weight: ≥60 to <70 kg: 35 mg, ≥70 to <80 kg: 40 mg, ≥80 to <90 kg: 45 mg, ≥90 kg: 50 mg
Are there any ongoing clinical trials and emerging therapies investigating novel thrombolytics and strategies to optimize efficacy while minimizing bleeding risk?
PEITHO-3 is a large, randomized, double-blind, multinational study comparing reduced-dose intravenous alteplase with standard heparin in patients with intermediate-high-risk PE.
References
Sedhom R, Megaly M, Elbadawi A, et al. Contemporary national trends and outcomes of pulmonary embolism in the United States. Am J Cardiol. 2022;176:132-138. doi:10.1016/j.amjcard.2022.03.060
Marti C, John G, Konstantinides S, Combescure C, Sanchez O, Lankeit M, Meyer G, Perrier A. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015 Mar 7;36(10):605-14. Epub 2014 Jun 10.
Zuo Z, Yue J, Dong BR, Wu T, Liu GJ, Hao Q. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2021;CD004437.
Feltes J, Popova M, Hussein Y, Pierce A, Yamane D. Thrombolytics in cardiac arrest from pulmonary embolism: a systematic review and meta-analysis. J Intensive Care Med. 2023;39(5):477-483.
Javaudin F, Lascarrou JB, Le Bastard Q, Bourry Q, Latour C, De Carvalho H, Le Conte P, Escutnaire J, Hubert H, Montassier E, Leclère B; Research Group of the French National Out-of-Hospital Cardiac Arrest Registry (GR-RéAC). Thrombolysis during resuscitation for out-of-hospital cardiac arrest caused by pulmonary embolism increases 30-day survival: findings from the French National Cardiac Arrest Registry. Chest. 2019 Dec;156(6):1167-1175. Epub 2019 Aug 2.
Bonnard T, Tennant Z, Niego B, Kanojia R, Alt K, Jagdale S, Law LS, Rigby S, Medcalf RL, Peter K, Hagemeyer CE. Novel thrombolytic drug based on thrombin cleavable microplasminogen coupled to a single-chain antibody specific for activated GPIIb/IIIa. J Am Heart Assoc. 2017 Feb 3;6(2):e004535.
Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e419S-e496S. Erratum in: Chest. 2012 Dec;142(6):1698-1704.
Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, Gent M. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest. 1990 Dec;98(6):1473-1479.
Rivera-Lebron B, Weinberg AS. Acute pulmonary embolism in adults: Reperfusion therapy in intermediate- and high-risk patients. In: Connor RF, ed. UpToDate. Waltham, MA: UpToDate Inc. Accessed August 28, 2025.
43 min
March 05443. Pulmonary Embolism: The Modern Approach to Pulmonary Embolism Care with Dr. Kenneth Rosenfield
This inaugural episode of the CardioNerds Pulmonary Embolism (PE) Series explores the evolution of acute PE care. Dr. Ibrahim Zahid, Dr. Dinu Balanescu, and Dr. Billy Joe Mullinax join guest expert Dr. Kenneth Rosenfield to discuss the shifting landscape of PE management.
Pulmonary embolism (PE) remains a leading cause of cardiovascular mortality and a frequent diagnostic challenge, often masquerading as myocardial infarction or a benign illness. Over the past decade, PE care has evolved from anticoagulation-only strategies to nuanced, risk-stratified, multidisciplinary management. Modern approaches integrate hemodynamics, biomarkers, and advanced imaging to guide therapy, including catheter-directed interventions and large-bore thrombectomy. The Pulmonary Embolism Response Team (PERT) model addresses historical gaps by coordinating rapid, multispecialty decision-making and standardizing care pathways. The PERT Consortium further advances PE care through education, research, and the world’s largest PE registry, while fostering leadership and research opportunities for trainees. Despite advances, long-term outcomes and post-PE syndromes remain important areas for future investigation. Audio editing by CardioNerds Academy intern, student doctor, Pace Wetstein.
Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.
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Pearls
PE is a “master masquerader”—maintain suspicion for atypical presentations like myocardial infarction, heart failure, flu, or anxiety.
Multidisciplinary management mediated through pulmonary embolism response teams improves outcomes and standardizes care.
Risk stratification integrates hemodynamics, biomarkers, and imaging.
Advanced therapies have expanded beyond anticoagulation.
Long‑term follow‑up and post‑PE syndrome need more research.
Notes
Notes: Notes drafted by Dr. Ibrahim Zahid.
1. How has the clinical approach to PE changed over the past decade?
PE is the third leading cause of cardiovascular death and historically under‑recognized.
Symptoms mimic MI, HF, asthma, syncope, and more.PE is a silent killer, and it should be recognized more as a cause of spontaneous cardiac arrest.
Where life threatening disease like stroke which is owned by neurological specialists and MI is primarily managed by cardiac specialists, PE is an entity without a professional home. The PERT Consortium brings the specialties together for PE care.
2. Ten years ago, a 58-year-old patient with a large bilateral PE, RV dilation, and positive biomarkers might have been managed with anticoagulation and close observation alone. Today, with evolving—but still uneven—data on advanced therapies, PE care feels far more nuanced and highly dependent on where you practice. What are the major gaps in traditional PE management that clinicians should recognize, and what care pathways should they be aware of across different hospital systems?
Care has shifted from anticoagulation‑only to multidisciplinary approaches like catheter directed thrombectomy.
Risk‑based pathways and the use of CT angiogram has improved early recognition. Risk stratification tools must be used as tools for early recognition of intermediate risk PE.
Untreated PE leads to chronic complications like chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension, which requires long term clinic follow up.
3. What is the role of risk stratification tools such as PeSI, sPeSI scores, cardiac biomarkers, and imaging findings in PE, and how do they guide treatment decisions in real world practice?
Integrate vitals (blood pressure and heart rate), biomarkers (troponin, pro-BNP), RV/LV ratio assessment, acid‑base status, and scores.
Tools include PESI, sPESI, BOVA, HESTIA, FAST, Geneva, NEWS, shock index.
Vitals, lactate, acid-base status, and tools like NEWS or shock index track clinical evolution.
PESI/sPESI estimate 30-day mortality and help identify low-risk patients who may be candidates for early discharge or outpatient therapy.
Clinical judgment matters—scores don’t fully capture clot burden, trajectory, or bleeding risk.
4. How was the pulmonary embolism response team created, and since its creation, what evidence or outcome data became available to support the PERT model?
Originated after a sentinel case at MGH: A young, pregnant woman in her 30s, who collapsed at home, underwent thrombectomy, and had to be on ECMO for a few days. The case brought cardiology, cardiac surgeons and critical care physicians together for planning and improvement in her health, which was rewarding.
Thereby, it was decided to bring specialties involved in PE care together to create a response team.
The name of the team, Pulmonary Embolism Response Team (PERT), was coined by Richard Channick in the first meeting.
Posters were set up all over the hospital to call a centralized line when an acute PE is recognized
A meeting was held to present the concept of putting together a consortium, with development of action items and a PERT database.
Enabled rapid multidisciplinary input using early teleconferencing tools.
5. Given concerns about having too many ‘cooks in the kitchen’ during the initial PE call—especially with rotating teams—how can institutions reconcile workflow complexity with standardized pathways in a way that meaningfully supports and justifies the added burden on frontline clinicians?
Every hospital’s PERT is different, catering to their needs and workflow
At least two disciplines are needed to make a PERTData is currently being collected to guide further on how the workflow can be standardized
Most importantly, the team brings in resources that were not available prior to PERT formation.
6. What are the main goals of the PERT consortium, and how does it support clinicians and institutions involved?
To improve care and improve outcomes for patients with PE
Expand education, refine algorithms, standardize care with Centers of Excellence.
Maintain the largest PE registry for research and outcomes improvement.
7. Beyond global networking, shared learning from successful systems, and the pathway toward Center of Excellence designation, what additional benefits can clinicians and health systems gain by participating in the PERT Consortium?
The ability to learn from other systems, the ability to share experiences.
Allow people to develop their professional careers like leadership experience, becoming a member of the trainee council
Initiate projects and receive funding for your ideas
8. For trainees interested in pulmonary embolism care, how can a trainee be a champion at their institution? Does PERT provide assistance and how can they really contribute meaningfully even before becoming a fellow/attending?
Medical students and residents interested in PE should reach out to the consortium and the consortium will hook you up with the correct mentors who can nurture you along.
Listen to the podcasts.
Participate with your local PERT team
PERT wants involvement of people who are social media savvy to help spread the word on PE.
Top three take-away points from this episode
Acute PE care has advanced and multiple treatment modalities for acute PE including catheter directed therapy, large bore thrombectomy, are becoming standard of care.
Multidisciplinary models like PERT improve coordination and outcomes.
Trainees play a vital role in advancing PE care through involvement, research, and education
References
Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jiménez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ní Áinle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. PMID: 31504429. https://pubmed.ncbi.nlm.nih.gov/31504429/
Rosovsky R, Zhao K, Sista A, Rivera-Lebron B, Kabrhel C. Pulmonary embolism response teams: Purpose, evidence for efficacy, and future research directions. Res Pract Thromb Haemost. 2019 Jun 9;3(3):315-330. doi: 10.1002/rth2.12216. PMID: 31294318; PMCID: PMC6611377. https://pmc.ncbi.nlm.nih.gov/articles/PMC6611377/
Rosenfield K, Bowers TR, Barnett CF, Davis GA, Giri J, Horowitz JM, Huisman MV, Hunt BJ, Keeling B, Kline JA, Klok FA, Konstantinides SV, Lanno MT, Lookstein R, Moriarty JM, Ní Áinle F, Reed JL, Rosovsky RP, Royce SM, Secemsky EA, Sharp ASP, Sista AK, Smith RE, Wells P, Yang J, Whatley EM; Pulmonary Embolism Research Collaborative (PERC) Attendees. Standardized Data Elements for Patients With Acute Pulmonary Embolism: A Consensus Report From the Pulmonary Embolism Research Collaborative. Circulation. 2024 Oct;150(14):1140-1150. doi: 10.1161/CIRCULATIONAHA.124.067482. Epub 2024 Sep 12. PMID: 39263752; PMCID: PMC11698503. https://pubmed.ncbi.nlm.nih.gov/39263752/
Sharifi M, Awdisho A, Schroeder B, Jiménez J, Iyer P, Bay C. Retrospective comparison of ultrasound facilitated catheter-directed thrombolysis and systemically administered half-dose thrombolysis in treatment of pulmonary embolism. Vasc Med. 2019 Apr;24(2):103-109. doi: 10.1177/1358863X18824159. Epub 2019 Mar 5. PMID: 30834822. https://pubmed.ncbi.nlm.nih.gov/30834822/
Pandya V, Chandra AA, Scotti A, Assafin M, Schenone AL, Latib A, Slipczuk L, Khaliq A. Evolution of Pulmonary Embolism Response Teams in the United States: A Review of the Literature. J Clin Med. 2024 Jul 8;13(13):3984. doi: 10.3390/jcm13133984. PMID: 38999548; PMCID: PMC11242386. https://pubmed.ncbi.nlm.nih.gov/38999548/
Rivera-Lebron B., McDaniel M., Ahrar K., Alrifai A., Dudzinski D.M., Fanola C., Blais D., Janicke D., Melamed R., Mohrien K., et al. Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium. Clin. Appl. Thromb. Hemost. 2019;25:1076029619853037. doi: 10.1177/1076029619853037.
https://pubmed.ncbi.nlm.nih.gov/31185730/
26 min

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