Venous thromboembolism (VTE), the combined syndromes of deep vein thrombosis (DVT) and pulmonary embolism (PE), is currently the third most frequent acute cardiovascular syndrome globally behind myocardial infarction and stroke.1 In the past decade, we have seen a remarkable improvement in new diagnostic tools as well as novel therapeutic options to manage patients with VTE.
Multiple societies from around the globe have published guidelines for the management of VTE. The most recently updated document is the 2019 European Society of Cardiology (ESC) guidelines for the diagnosis and management of acute pulmonary embolism, which was developed in collaboration with the European Respiratory Society (ERS).2 A major limitation of the currently published guidelines is its complexity.
To aid healthcare providers caring for patients with acute PE, our team developed a novel, comprehensive yet straightforward, pathway for the management of patients with PE, which we believe can be used in many healthcare systems around the globe (Fig. 1).
The necessity to develop such a pathway at our institution was compelling and typical of the need at many other large medical centers. It has become increasingly difficult for all healthcare providers to grasp all the subtleties in the management of VTE to rapidly, efficiently, and accurately implement clinical protocols. It should be emphasized that this pathway is the opinion of our group and may differ somewhat from the published guidelines.
Our pathway for the diagnosis and management of pulmonary embolism is divided into 3 steps as demonstrated in Figure 1:
Step 1: Diagnosis of PE (top third of pathway)
Step 2: Acute management of patients with PE (middle third of pathway)
Step 3: Recommendations for the chronic management of patients with PE (the bottom third of the pathway).
In each step, we propose key questions that lead to “yes” and “no” answers which will further aid the healthcare providers to easily navigate the pathway.
The Pulmonary Embolism Response Team (PERT) is a multispecialty team involved in the decision-making for the individual patient. The ESC guidelines recommend establishment of a team of experts to convene for every case of intermediate- or high-risk pulmonary embolism. The composition of the team depends on the local resources and expertise. The PERT team brings together specialists from different disciplines including, but not limited to, cardiology, pulmonology, Emergency Medicine, hematology, vascular medicine, anaesthesiology/intensive care, cardiothoracic surgery, and interventional radiology. The team convenes in real time (via a platform such as WhatsApp or text messages) to communicate clinical data, discuss the options, and provide consensus for a course of management. By directly involving the expert clinicians, the team facilitates the immediate implementation of the care plan.3
DESCRIPTION OF THE PATHWAY
In most cases, patients with PE present with dyspnea, chest pain, presyncope or syncope, or hemoptysis. However, in other cases, the signs and symptoms may be nonspecific.
Acute Management of Hemodynamically Unstable Patients
The first action is to assess the hemodynamic status in any patient with suspected PE (Fig. 2). Hemodynamic instability is defined as one of the following:
- Presentation following cardiac arrest or current need for cardiopulmonary resuscitation.
- Obstructive shock—defined as systolic BP < 90 mm Hg or vasopressors required to achieve a BP > 90 mm Hg despite adequate filling status AND end organ hypoperfusion (altered mental status, cold, clammy skin, oligo-anuria, increased serum lactate).
- Persistent hypotension—defined as systolic BP < 90 mm Hg or systolic BP drop > 40 mm Hg from baseline, lasting longer than 15 minutes and not caused by a new onset arrhythmia, hypovolemia, or sepsis.
In patients with hemodynamic instability, the most useful initial test is bedside transthoracic echocardiography (TTE). The bedside TTE will show evidence of significant acute RV dysfunction if acute PE is the cause of the patient’s hemodynamic decompensation. This hemodynamically unstable patient is defined in our pathway as a “High Risk PE” and the PE Response Team (PERT team) should be activated. In a highly unstable patient, who cannot be mobilized to CT angiography, TTE evidence of RV dysfunction is sufficient to prompt initiation of anticoagulation with heparin and initiation of reperfusion strategy without further testing. In centers where computed tomography pulmonary angiogram (CTPA) is immediately available and feasible, a diagnosis of PE should be confirmed before proceeding to a reperfusion strategy.
Primary reperfusion is the treatment of choice for patients with high-risk PE and can be achieved by thrombolysis and/or embolectomy. Thrombolysis can be achieved by a systemic treatment or preferably by a catheter directed treatment. Embolectomy can be performed surgically or by a catheter directed approach.
Following reperfusion treatment and hemodynamic stabilization, the patient should be hospitalized in a critical care unit. As patients continue to recover, they can be switched from parenteral to oral anticoagulation before discharge home.
Acute Management of Hemodynamically Stable Patients
In patients who are hemodynamically stable, the combination of symptoms, clinical findings, and presence of predisposing factors for VTE allows the classification of patients with suspected PE into distinct categories of clinical or pretest probability of PE (Fig. 3). This pretest assessment can be done either by clinical judgment or by using prediction rules. Clinical judgment lacks standardization and therefore several prediction scores have been developed. Of those the most frequently used and the ones we recommend using are the simplified “Revised Geneva” rule4 and the simplified “Wells” rule.5 Regardless of the score used, the proportion of patients with conformed PE is expected to be 10% in the low-probability group, 30% in the intermediate-probability, and 60% in the high-probability groups.6
We recommend multidetector CTPA as a first line test in patients with a high-clinical probability of PE. CTPA is considered to be diagnostic of PE when it shows a clot at least involving the segmental level of the pulmonary arterial tree. In patients with low- or intermediate-clinical probability of PE, we recommend measuring the plasma D-dimer as a first step and then proceeding to CTPA in patients with an elevated D-dimer level.2,7
For most cases of acute PE without hemodynamic compromise, parenteral or oral anticoagulation is adequate treatment. We suggest testing these stable patients for antiphospholipid antibodies (APLA), for those with positive APLA tests, especially triple positive APLA, we recommend starting treatment with low-molecular weight heparin (LMWH) and long-term treatment with warfarin.8 Otherwise treatment with direct oral anticoagulants (DOACS) is generally recommended.
Risk stratification of patients with acute PE is mandatory for determining the appropriate next therapeutic management step. To assess PE severity to guide treatment, we recommend a 2-step approach integrating clinical, imaging, and laboratory findings.
The first step combines the clinical evaluation and the assessment of RV dysfunction on TTE or CTPA.
Of the clinical scores integrating PE severity and comorbidity, the Pulmonary Embolism Severity Index (PESI) has been most extensively validated and its simplified version is the one we recommend in our algorithm.9 To aid healthcare providers who may use this score as a simple way to assess risk, the score can be remembered in the following way: “80, 90, 100, 110 CC.” “Eighty” is the age of over 80 years old, “90” is the arterial oxyhemoglobin saturation of less than 90%, “100” is systolic BP of less than 100 mm Hg, “110” is heart rate over 110 beats per minute, the first “C” stands for cancer, and the second “C” stands for either chronic heart failure or chronic pulmonary disease. Each of these 6 parameters gets a score of 1 so the total score ranges from 0 to 6. Based on the simplified version score,9 0 total points translates to 30-day mortality risk of 1% while a score of 1 or more translates to 30-day mortality risk of 10.9%.
In patients with either sPESI score of at least 1 and RV dysfunction on TTE or CTPA, further work up should include assessment of cardiac biomarkers for evidence of myocardial injury: elevated troponin or myocardial stretch, B-type natriuretic peptide (BNP), and N-terminal (NT) proBNP.
Patients who are “triple” positive (sPESI score of 1 or more with RV dysfunction on imaging and positive cardiac biomarkers) are considered “intermediate high-risk PE.” The PERT team should be activated for these patients with consideration of initiation of catheter-directed therapy, typically catheter-directed local thrombolysis. These patients are at a higher risk of early hemodynamic decompensation and circulatory collapse and they should be monitored in a critical care unit.
Patients who have either sPESI score of one or more and RV dysfunction on TTE or CTPA, but their cardiac biomarkers are negative are considered “intermediate low risk.” These patients do not require additional reperfusion strategy beyond their anticoagulation therapy and they should be admitted to a general cardiology or medical floor.
There is a small group of patients with acute PE in whom the sPESI score is 0 and imaging modalities exclude RV dysfunction. These patients are considered as “low risk PE.” Early discharge and continuation of anticoagulant treatment at home should be considered if they meet the following three criteria: (1) There are no other reasons for hospitalization. (2) There is adequate family or social support. (3) There is easy access to medical care.
To summarize the diagnosis and management of patients with acute PE, we have developed the HADASSAH mnemonic to help healthcare providers memorize the key points in our algorithm (Fig. 4). The key points are hemodynamic instability, akinetic RV and assessment probability of PE, D-dimer test and defect on CTPA, anticoagulation and activation of PERT team, simplified severity score of PE, angiogram for catheter-directed therapy, and hospital location to home.
Chronic Management of Patients With Acute PE
The goal of anticoagulation after acute PE is to complete the treatment of the acute episode and to prevent recurrence of VTE over the long term (Fig. 5). Oral anticoagulants are highly effective in preventing recurrent VTE during treatment, but they do not eliminate the risk of subsequent recurrence after discontinuation of the treatment. Considering the bleeding risk of anticoagulation treatment, the key question is how to select patients for extended or indefinite anticoagulation.
Based on the 2019, ESC guidelines for the diagnosis and management of PE, all patients with PE should be treated with anticoagulation for at least 3 months.1,10 We recommend continued anticoagulation for a period of 3–6 months and following these patients in a specialty coagulation clinic if available. The direct oral anticoagulation (DOAC) agents are recommended by our team as a first choice based on their excellent safety profile and their excellent extended treatment data.11–13
The key question at this point is to define who will benefit from an extended therapy beyond the first 3–6 months of anticoagulation. We recommend two steps work up:
- The first step involves 3 tests: Duplex ultrasound to rule out lower extremities DVT, TTE to assess the RV function, and pulmonary hypertension and a blood test for D-dimer. A positive finding in any of these tests will mandate continuation of anticoagulation for a longer period of time.
- The second step is the clinical assessment of these patients in regards to persistence of symptoms (dyspnea and persistent functional limitations), evidence of severe thrombophilia, and exclusion of a prior major provocation (>3 days in bed, malignancy, or a major surgery or trauma).
If the entire work up is negative, we recommend discontinuing the anticoagulation therapy but to consider prophylaxis in high-risk situations.
The patency of the pulmonary arterial bed is restored in the majority of PE survivors within the first few months following the acute episode; therefore, no routine follow-up CTPA imaging is needed. However, in a very small group of patients, thrombi become persistent and organized, which in rare cases may result in chronic thromboembolic pulmonary hypertension (CTEPH), a potentially life-threatening condition. We recommend that these patients be followed in a CTEPH specialty clinic.
Nothing to declare.
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