Show notes
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.