CardioNerds (Amit and Dan) join join Dr. Andrew Dicks (Vascular medicine physician at Prisma Health, former fellow at Mass General Vascular) and Dr. Prateek Sharma (Vascular interventional & medicine fellow at MGH) for an ice-cold drinks at the Esplanade in Boston, MA to discuss a case about a patient who developed a pulmonary embolism and masterfully discuss the diagnosis and management of of pulmonary emboli. Dr. Ido Weinberg (Director, Vascular Medicine Fellowship at MGH) provides the ECPR for this episode.

Case Abstract: A 59-year-old Spanish-speaking man with no significant past medical history presents after falling 15-20 feet from a ladder and landing on his back. He was found to have an L1 fracture and left radial fracture and underwent T12-L2 fusion with neurosurgery on hospital day 1 and ORIF of left radial fracture with orthopedic surgery on hospital day 2. On hospital day 5, he develops acute onset tachycardia with HR in the 130s bpm with new O2 requirement associated with mild shortness of breath at rest without any chest discomfort. His labs were notable for an elevated troponin and proBNP. He underwent CTPA which demonstrated acute bilateral occlusive pulmonary emboli (PE) extending in the right and left main pulmonary arteries. TTE demonstrated right ventricle dilation. The patient was started on a heparin infusion and a PE response team (PERT) meeting was held to discuss treatment options. Given recent surgery, use of thrombolytic therapy was felt to be too risky and thus he was taken for percutaneous thrombectomy in the cath lab. PA pressure prior to intervention was 51/21 mmHg. The patient underwent suction thromboembelectomy with the Flow Triever device with extraction of thrombus and improvement in PA pressure to 19/11 mmHg. He was treated with anticoagulation thereafter and discharged home two days after the procedure.

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Case Media

Acute bilateral occlusive and nonocclusive pulmonary emboli extending from the right and left main pulmonary arteries to the lobar and segmental arteries of all the lobes.  Moderate right heart strain including the right atrium and the right ventricle. RV/LV ratio > 1.0.

Right ventricular cavity is dilated (RV size at the base measures to 45mm). Right ventricular systolic function is moderately decreased. Right ventricular free wall is hypokinetic with sparing of the right ventricular apex consistent with acute right ventricular strain

Pulmonary angiography demonstrated extensive proximal bilateral PEs



Caption: Post-procedure TTE demonstrated resolution of RV strain with normalization of RV size and function.

Episode Schematics & Teaching

Pearls

1. While there are markers to suggest PE, such as ECG findings or evidence of RV dilatation, a PE cannot be confirmed without imaging.
   
2. Elevation of cardiac biomarkers and evidence of RV dysfunction are used to risk stratify PE, not the degree of thrombus burden or locale of thrombus.
   
3. Enoxaparin is the preferred anticoagulant to initiate at time of PE diagnosis if comorbidities allow.
   
4. Optimal treatment of intermediate risk PE remains uncertain as there is little data about long-term outcomes. Aggressive treatment should be used judiciously and chosen on a case-by-case basis.
   
5. PE response teams (PERT) allow for multidisciplinary expert opinion in the face of scarce evidence to determine what is felt to be the best management strategy.
   

Notes

1. What is a PERT team and why is it helpful?

• We have several tools and approaches for the management of PE. There are also many subspecialities involved in the care of patients with PE, including vascular medicine, intervention cardiology, hematology, pulmonology, cardiac surgery, radiology, emergency department, intensive care, and more. As such, the best treatment plan for a given patient with PE can be challenging, especially if the services involved in treatment of the PE function in silos.
  
• PERT, or PE Response Team, was built to address this concern. It is a multidisciplinary team that originated at MGH whose goal is to coordinate care for high-risk PE patients and advance PE-related care in the institution.
  
• PERT allows for multidisciplinary expert opinion in the face of scarce evidence to determine what is felt to be the best management strategy.
  

2. How do we risk stratify patients with PE?

• Risk stratification is largely dependent on the hemodynamic significance caused by the PE. In addition to vital sign derangement, patients with PE should also be evaluated for evidence of cardiac strain due to PE by checking for evidence of RV dilatation on CT or TTE and for elevation of cardiac biomarkers. The combination of this information is used to risk stratify patients. Additionally, risk stratification tools, such as the PESI and sPESI scores, are used to guide risk stratification.
  
• Based on the ESC 2019 guidelines, PEs are stratified into high risk, intermediate-high risk, intermediate-low risk, or low risk.
  
  • High risk: evidence of hemodynamic instability as defined by hypotension or shock.
    
  • Intermediate-high risk: evidence of both RV dysfunction on imaging AND elevated cardiac biomarkers in the absence of HD instability
    
  • Intermediate-low risk: evidence of either RV dysfunction on imaging OR elevated cardiac biomarkers in the absence of HD instability
    
  • Low risk: no evidence of cardiac dysfunction on imaging or labs and no evidence of HD instability.
    
  
  
• Risk stratification is important as it helps guide medical management of patients. Important factors that have not been associated with PE severity include degree of thrombus burden and location of clot.
  

3. What do we know about optimal management of patients with intermediate risk PE?

• Unfortunately, data is fairly limited with regards to the optimal management strategy for patients with intermediate risk PE, namely whether anticoagulation alone is sufficient versus if a patient would benefit from more advanced therapies. All patients should be started on anticoagulation, preferably SQ enoxaparin if comorbidities allow, as soon as possible (if there are no contraindications to anticoagulation). However, choosing which patients would benefit from more advanced therapies remains limited.
  
• Thrombolysis has been associated with lower all-cause mortality in patients with intermediate-risk PE when compared to anticoagulation alone. However, not surprisingly, thrombolysis was also associated with more major bleeding, including intracranial hemorrhage. In the ULTIMA trial, catheter directed thrombolysis was shown to improve RV dysfunction more quickly compared to anticoagulation at 24 hours. However, at 90 days, there was no difference in degree of RV dysfunction between the two groups.
  
• Percutaneous thrombectomy devices have been shown to be safe and effective at reducing RV size. However, there are no head-to-head comparisons of these modalities versus anticoagulation or thrombolysis and data is limited regarding the long-term efficacy.
  
• Choosing the correct patient to proceed with advanced therapies remains challenging and the decision is often made on a case-by-case basis. There are ongoing randomized control trials that will hopefully assist in guiding this decision making.
  

4. What about management for those with high-risk PE?

• High risk PEs mandate aggressive and rapid treatment.
  
• Thrombolysis has been shown to have a mortality benefit compared to anticoagulation. 
  
• Catheter directed thrombolysis can be considered in high-risk PE; however, rapid implementation needs to be available.
  
• VA-ECMO has also been demonstrated to reduce mortality in these patients.
  

5. What additional treatment options are available for patients with PE who are not improving on anticoagulation and have a contraindication to thrombolytic therapy?

• There are several contraindications to thrombolytic therapy, including recent surgery, CVA, or bleeding. Percutaneous and surgical thrombectomy should be considered in these patients.
  
• Surgical thrombectomy is effective but does require significant anticoagulation during the surgery while the patient is on cardiac bypass. For this reason, patients that have a contraindication to thrombolysis might not be able to tolerate the high levels of anticoagulation required for the surgery and thus a surgical thrombectomy might not be a feasible option.
  
• There are several percutaneous thrombectomy devices on the market currently which have been shown to be safe and effective at reducing the RV size in the acute period. Because these devices do not require thrombolytic agents, the risk of bleeding is lower and there is less ICU utilization. However, there have not been head-to-head comparisons between these devices and other treatment modalities.
  

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). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405
   
2. Robertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2017;2:CD001100. doi:10.1002/14651858.CD001100.pub4
   
3. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411. doi:10.1056/NEJMoa1302097
   
4. Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421. doi:10.1001/jama.2014.5990
   
5. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129(4):479-486. doi:10.1161/CIRCULATIONAHA.113.005544
   
6. Subramaniam RM, Mandrekar J, Chang C, et al. Pulmonary embolism outcome: a prospective evaluation of CT pulmonary angiographic clot burden score and ECG score. AJR Am J Roentgenol. 2008;190(6):1599-1604. doi:10.2214/AJR.07.2858
   
7. Jain CC, Chang Y, Kabrhel C, et al. Impact of Pulmonary Arterial Clot Location on Pulmonary Embolism Treatment and Outcomes (90 Days). Am J Cardiol. 2017;119(5):802-807. doi:10.1016/j.amjcard.2016.11.018
   
8. Tu T, Toma C, Tapson VF, et al. A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study. JACC Cardiovasc Interv. 2019;12(9):859-869. doi:10.1016/j.jcin.2018.12.022