A 54-Year-Old Woman With Shortness of Breath: Part 2
Correct Answer: C
Discussion. The imaging findings confirmed the suspected diagnosis of PE anatomically.1 In fact, the PE involved at least two lobar arteries (of five) and by older literature would have been termed “massive” as at least 40% of the vasculature is affected.2 A cardiac EKG revealed normal ejection fraction except for the presence of flattening of the interventricular septum.
Currently, such terminology and anatomic definitions are less in favor and the degree of pathophysiology impact is more emphasized when assessing initial management strategies. There are two basic sets of data used to do this, (1) via laboratory parameters and (2) by imaging not of the PE itself, but rather of the heart’s response to it. As given in the stem, cardiac echography findings are used to detect right heart strain and include the presence of right ventricular hypertrophy, or, as was the case here, flattening and displacement of the interventricular septum. Any of these is evidence of RV strain. The biochemical markers of strain include either spillage of troponins or elevated levels of brain natriuretic peptide.3 The troponin of 0.08 was already known so there are two findings present here for unequivocal right heart strain. Next, we fit these findings into current schemata and guidelines for PE therapy.
Currently, the literature supports risks stratification schemes, each of which has a core basic therapy. Within each of these are subsets of management. For example, high risk PE cases, about 5%, mean just that—life threatening PE the extent of which must be essentially immediately reversed via re-perfusion techniques rather than supporting the patients and preventing new emboli while awaiting for the body’s quite excellent and rapid fibrinolytic system to clear the emboli. Patients considered “high risk” will be identified by serious physiologic alterations wherein the extent of pulmonary vascular occlusion is causing severe, life threatening ventilation/perfusion abnormality with profound arterial hypoxemia, similarly severe strain of the RV and diminished filling of the LV with diminished organ perfusion resulting in hypotension (> 40 mmHg) from baseline blood pressure or absolute systolic blood pressure (< 90 mmHG), which can be so severe as to cause syncope (2). The most convenient treatment modality to address this situation is to administer systemic thrombolytics such as alteplase 100 mg given over 1-2 hours.4 Although previous studies have examined catheter-directed thrombolysis and even catheter-directed direct thrombectomy, neither of these have demonstrated superiority of systemic lysis, and both require a level of expertise not widely available and take more time from so called “door to needle” criteria.4,5 Thus, Answer B is not the correct answer.
On the other end of the risk spectrum are those patients deemed “low risk” who are hemodynamically stable and show no imaging or biochemical findings of right heart strain. These patients, which are a majority of PE cases, are effectively managed by anticoagulants, and it is this group who have been maximally benefited by the explosion of new, effective anticoagulants that have become available in recent decades. Many effective, easy-to-use oral agents have FDA approval for PE indication—namely, rivaroxiban and epixiban. Strong sponsored clinical trials have repeatedly shown efficacy, minimal toxicity, lack of need for monitoring, and ease of administration equivalency or superiority compared to classical heparin/warfarin therapy.5,6 The basic cautions are as simple as judging bleeding risks and keeping an eye on creatinine such that drug accumulation does not occur. Many patients who are clinically stable and have good home support with follow-up arranged can be discharged to their homes.3,6 Thus a trip to the ER with appropriate studies for PE diagnosis and subsequent discharge has replaced to the 5(+) day heparin/warfarin in hospital management of the past. Therefore, Answer D is not correct.
This leaves the “intermediate risk” group of patients with PE. These patients are deemed “intermediate” because they do not manifest profound hypoperfusion with severe hypoxia, nor hypotension as described. However, they do manifest the more subtle radiologic and biochemical parameters of right heart strain. Again, strong studies have provided excellent guidance for management. It turns out that in such populations, only 1 of 20 will deteriorate and develop shock.7 Trials have also demonstrated that when patients in the intermediate population are given thrombolytics, although there is a 3% reduction in development of shock, the toxicity cost is prohibitive, specifically a 2% risk of hemorrhagic stroke along with a 9.2% risk of a major bleed.7 Therefore, these patients’ best management is to admit to an observed setting capable of monitoring for deterioration and use parenteral anticoagulants, either standard or (preferred) low molecular weight heparin, until the clinical situation clarifies itself at which time the NOAC’s can be used.7
Regarding longer-term therapy, the standards of care are quite strongly backed by good data. Some degree of “long-term” anticoagulation is needed and the NOACs have replaced most of the formal cumbersome warfarin prophylaxis of the past. There are, however, more nuances and “special situations” with follow-up therapy. Core follow-up therapy requires a 3-6 month oral anticoagulants after a PE at a minimum, the former used when an easily reversible risk factor is involved. In my experience, the ease and safety of the NOACs makes me open to a 6-month course in essentially all PE cases. I then review data and clinical status, and then repeat leg dopplers and biochemical testing. When a reversible risk factor, e.g. leg fracture, post op PE, exists and is gone, then therapy can stop. If this is not the case, as with active cancer, or if the PE was unprovoked or if there is a total history of more than one thromboembolic event, then “indefinite” anticoagulation with 50% dose reduction in NOACs is used.3,8 Of course, 6 or 12-month interval evaluations along with creatinine monitoring is required, and decisions can change at a later time. Special situations include pregnancy, which requires the use of LMWH or so called “triple positive” anticardiolipin antibody for patients who require warfarin as their prophylaxis.9
As stated in part one of this two-part series, most of the prognoses for PE involve the co-morbid conditions that predisposes to it, e.g. the 20% 90-day mortality overall. In the PE population presenting de-novo to an outpatient setting, however, the 90-day mortality is 5%3. There are studies quoting a 50% incidence in functional and exercise limitations at 1 year.10 And there is the ever-present comment in so many studies of patients with diagnoses of “diminished” quality of life issues.11 Regarding these findings, in my experience, I prefer objective clinical findings to subjective, broad questionnaires. The authors of those studies generally concluded that the functional and exercise limitations were due to deconditioning after the acute PE since mean PFT and echocardiographic results (pulmonary artery pressure, right and left ventricle systolic function) were normal and similar to the 50% without such limitations10. But in my experience, an overwhelming majority do very well, and the advent of NOACs are certainly helping these patients. In most cases, the prognosis is quite good.
Regarding the remaining answers, vena cava filters have an extremely limited place in PE management and is not recommended by CHEST or ASH guidelines except in the presence of an absolute contradiction to anticoagulation. Mechanical thrombectomy is not yet standard of care and needs more data/trials at this time. The presence of a hypercoagulable state does not alter initial management of PE, is notoriously inaccurate in the acute setting with anticoagulants/lytics in place and should be done in the outpatient setting later in the course of management. Thus A and E are incorrect choices.
Patient follow-up. The patient was admitted to an acute care area with frequent VS monitoring. Nasal cannula O2 was administered an LMWH initiated. Very quickly after O2 was given pulse oximetry rose to 96% and within 12 hours, BP had risen and was stable in the 125/80 range. By day 3, all VS were normal and O2 saturation was 96% on room air. LMWH was stopped and apixaban was initiated. The plan is to continue therapy for 6 months. In the interim age/sex appropriate cancer screenings will be performed. Reevaluation and hypercoagulation tests will be performed at 6 months and decisions on duration of anticoagulation made at that time.
What’s The Take Home? Management of acute PE has significantly improved in the last decade due to availability of NOAC anticoagulants (easy oral administration, excellent safety data, no need for monitoring) with large numbers of well-done randomized trials testing therapy schemas available. Once confirmed, the acute PE clinical scenario needs be classified as either high risk, intermediate or low risk. High risk cases are those with dangerous levels and instability of vital signs, e.g. hypotension <90 mmHg and profound hypoxemia. These patients need immediate reperfusion usually in the form of thrombolytic therapies. Intermediate risk cases will have reasonable/stable VS but manifest markers of right ventricular strain either on imaging or biochemical markers (e.g. troponins, brain natriuretic peptide evaluations). These cases need admitting for monitoring stability, usually using LMWH as anticoagulant therapy. If there is deterioration (about 5% of cases) thrombolytics are used at that time. Low risk patients can be anticoagulated with NOACs and often discharged to home with good follow up. Once the acute phase has passed, NOACs in half dosage should be used for 3-6 months depending on case specifics at which time the anticoagulants can be either stopped or continued at the reduced dosage. With current diagnostics, risk stratification and therapeutic schemes the acute and long term prognosis of acute pulmonary embolism is very good.
- Rubin RN. A 54 year-old woman with shortness of breath: part 1. Consultant. 2023;63(5):e11. doi:10.25270/con.2023.04.000004
- Goldhaber SZ. Pulmonary embolism. N Eng J Med. 1998;339:93-104.
- Kahn SR and de Wit K. Pulmonary embolism. N Eng J Med. 2022;387:45-47.
- Jimenez D, Martin-Saborido C, Muriel A et al. Efficacy and safety outcomes of recanalization procedures in patients with acute symptomatic pulmonary embolism: Systemic review and network meta-analysis. Thorax. 2018;73:464-471.
- Stevens SM, Waller SC, Kreuzinger LB et al. Antithrombotic therapy for VTE disease: Second update of the CHEST guideline and expert panel report. Chest. 2021;160:e545-e608.
- 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;124:1968-1975.
- Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370:1402-1411.
- Kearon C, Kahn SR. Long-term treatment of venous thromboembolism. Blood. 2020;135:317-325.
- Bates S, Rajasekhar A, Middledorp S, et al. American society of hematology guidelines for management of venous thromboembolism: Venous thromboembolism in the context of pregnancy. Blood Adv. 2018;2:3317-3359.
- Kahn SR, Hirsch AM, Akaberi A, et al. Functional and exercise limitations after a first episode of pulmonary embolism: Results of the ELOPE prospective cohort study. Chest. 2017;151:1058-1068.
- Tavoly M, Utne KK, Jelsness-Jørgensen L-P, et al. Health-related quality of life after pulmonary embolism: a cross-sectional study. BMJ Open. 2016;6:e013086.
1Lewis Katz School of Medicine at Temple University, Philadelphia, PA
2Department of Medicine, Temple University Hospital, Philadelphia, PA
Rubin RN. A 54 year-old woman with shortness of breath: part 2. Consultant. 2023;63(6):e8. doi:10.25270/con.2023.06.000002.
The author reports no relevant financial relationships.
Ronald N. Rubin, MD, Temple University Hospital, 3401 N Broad Street, Philadelphia, PA 19140 (email@example.com)