Casey Briggs MD, Brett Curran MD, Philip Spencer MD
Mayo Clinic Rochester
August 25th, 2024
Abbreviations and Definitions
AHA – American Heart Association
BNP – Brain natriuretic peptide
DOAC – Direct oral anticoagulant
VA-ECMO – Veno-arterial extracorporeal membrane oxygenation
PE – Pulmonary embolism
PFO – Patent foramen ovale
RBBB – Right bundle branch block
RV – Right ventricle
SBP – Systolic blood pressure
VKA – Vitamin K antagonists
Indications and Guidelines for Management
All patients with a confirmed pulmonary embolism (PE) should have initial treatment with therapeutic subcutaneous or intravenous anticoagulation without contraindications. This may be considered for patients who have a high probability of PE during initial workup. Severity as defined by the American Heart Association (AHA) Guidelines for Management of Massive and Submassive Pulmonary Embolism is as follows:1
- Massive/High Risk PE: Acute PE with sustained systemic hypotension, defined as systolic blood pressure (SBP) <90 mmHg for 15 minutes or requiring inotropic support without another cause, pulselessness, or profound bradycardia.
- Submassive/Intermediate risk PE: Acute PE with or without systemic hypotension but with right ventricular (RV) dysfunction or myocardial necrosis. RV dysfunction is defined as dilation, systolic dysfunction, BNP/N-terminal Pro-BNP elevation, EKG changes of right bundle branch block (RBBB), anteroseptal ST elevation or depression, or anteroseptal T-wave inversion.
- Low Risk PE: Acute PE without markers defining massive or submassive PE.
Catheter-based interventions for PE include aspiration thrombectomy and thrombus fragmentation. Rheolytic thrombectomy has previously been included in the interventional armamentarium, though it has been labeled with a black box warning for application in the treatment of PE for pulmonary hemorrhage complications.
Summary Table
| Classification | Guidelines | Evidence |
|---|---|---|
| Massive/ High risk PE | Initiation of therapeutic anticoagulation Fibrinolysis if no contraindication Catheter-based intervention Complement fibrinolysis therapy Unstable after fibrinolysis Failed fibrinolysis Surgical embolectomy Consider if all other interventions fail Contraindication to fibrinolytic Concern for developing shock while awaiting effect of other therapies Screening echocardiogram to screen for patent foramen ovale (PFO) If impending paradoxical embolism, consider surgical embolectomy Mechanical circulatory support may be indicated to support hemodynamics | 1 |
| Submassive/ Intermediate risk PE | Initiation of therapeutic anticoagulation Fibrinolysis, catheter embolectomy, or surgical embolectomy if clinical evidence of worsening prognosis Screening echocardiogram to screen for PFO If impending paradoxical embolism, consider surgical embolectomy | 1, 2 |
| Low risk PE | Consider outpatient management on DOAC | 3 |
Supporting Evidence of Current Indications & Guidelines
- AHA Guidelines for Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension is a scientific statement to guide clinicians for appropriate management of patients and forms the basis for management guidelines. This is based on evidence and the consensus of a committee of experts.
- The PEITHO trial is the largest trial comparing tenecteplase plus heparin to heparin plus placebo in the treatment of patients with submassive PE. This study enrolled 1006 patients with the composite endpoint of reduced all-cause mortality or hemodynamic decompensation at seven days. The result of the trial showed a decrease in the primary endpoint, which was mostly driven by the decrease in hemodynamic decompensation of unclear significance. There was no mortality benefit. Alternatively, there was a significant increase in intracranial hemorrhage.
- Direct oral anticoagulants (DOAC) compared to Vitamin K antagonists (VKA) for acute venous thromboembolism: evidence from six phase 3 trials evaluated 27,023 patients treated with several DOAC vs VKA. The efficacy of DOAC and VKA was comparable, with a decrease in major bleeding events.
Ongoing Trials/Recent Publications
A recent scientific statement by the AHA addresses surgical management of high-risk PE. Historically, surgical management has been reserved for the salvage of PE treatment in the face of failure of other management modalities. However, there is a growing body of evidence that suggests excellent intermediate and long-term outcomes for patients who undergo surgical embolectomy, with patients who have not required CPR. There is comparable mortality to patients who undergo elective coronary artery bypass grafting at around 3%, despite the presence of acute RV failure at the time of embolectomy.4 Patients who failed fibrinolytic therapy and subsequently underwent surgical embolectomy had higher mortality from postoperative bleeding.4 This perspective may lead to a change in the treatment paradigm to expand the use of surgical embolectomy. Further studies are warranted to identify patients likely to fail fibrinolytic therapy and direct patients toward upfront surgical embolectomy.
Expert Commentary
When patients present with elevated cardiac markers, RV dysfunction, and hypotension (or stigmata of hypotension such as syncope), mechanical intervention should be pursued to prevent sudden death. Immediate surgical embolectomy, catheter-based thrombolysis or embolectomy, or hemodynamic support on VA-ECMO are all reasonable options. No evidence exists to suggest one leads to higher survival than another. We caution that if surgical embolectomy is pursued, the surgeon should remain in the operating room for induction and insist on higher-than-normal systemic blood pressure to support RV function. If catheter-based options are pursued or if the patient has contraindications to immediate mechanical embolectomy, such as recent administration of tPA, we would consider elective VA-ECMO prior to mechanical intervention. Goldberg et al. demonstrated equivalent survival with VA-ECMO support with systemic anticoagulation versus surgical embolectomy.4
Sources
- Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. 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 Apr 26;123(16):1788-830. doi: 10.1161/CIR.0b013e318214914f. Epub 2011 Mar 21. Erratum in: Circulation. 2012 Aug 14;126(7):e104. Erratum in: Circulation. 2012 Mar 20;125(11):e495. PMID: 21422387.
- Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galiè N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097. PMID: 24716681.
- van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014 Sep 18;124(12):1968-75. doi: 10.1182/blood-2014-04-571232. Epub 2014 Jun 24. PMID: 24963045.
- Goldberg, J.B., Spevack, D.M, Ahsan, A., Rochlani, Y., Ohira, S., Spencer, P.J., Kai, M., Malekan, R., Spielvogel, D., Lansman, S. Comparison of Surgical Embolectomy and Veno-arterial Extracorporeal Membrane Oxygenation for Massive Pulmonary Embolism. 2022, Autumn; 34(3):934-942. PMID: 34157383
