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The Diagnosis and Management of Acute Pulmonary Embolism in 2021: Evolving Strategies
Acute pulmonary embolism (PE) remains a major cause of morbidity and mortality worldwide. Death from sudden acute PE is often unexpected and, thus, too often unavoidable. The current era in acute venous thromboembolism (VTE) is characterized by improving risk stratification methods and novel therapeutic agents, as well as exciting anticoagulant reversal agents and clot extraction and dissolution techniques. The evolving clinical trial data are very convincing in some areas and less robust in others. As has been the case previously, a solid evidence base supporting new exciting technologies lags behind our enthusiasm to utilize them, rendering both expert opinion and carefully planned randomized clinical trials even more crucial. Thus, it is an opportune time to offer Seminars in Respiratory and Critical Care Medicine on acute PE. The articles offered in this issue are presented by experts in acute VTE from around the world.
While acute deep venous thrombosis (DVT) and PE certainly overlap, in this issue, we will focus more on patients who present with acute PE. Acute PE remains the leading preventable cause of death in hospitalized patients. Thus, while a dramatic reduction in mortality with anticoagulation has been clearly demonstrated in acute PE, patients are often not diagnosed or even suspected until after death. Drs. Ho, Bellamy, and Naydenov from St. Louis have provided us an outstanding look at where we stand with mortality from acute PE.
We have continued to rely on computed tomographic angiography and ultrasonography as the primary diagnostic imaging techniques for acute PE and DVT, respectively. Scoring systems, particularly in patients presenting to the emergency department, have been shown to reduce the need for diagnostic imaging. Drs. Douillet, Roy, and Penaloza have offered a brilliant and timely treatise on these scoring systems without underestimating the importance of clinical gestalt. They also highlight the evolving use of artificial intelligence that has penetrated essentially all areas of medicine including VTE. Once the diagnosis is made, risk stratification must be undertaken and a clear therapeutic plan outlined. Importantly, once patients are suspected, consideration of initiation of anticoagulation is critical—this should precede establishment of a firm diagnosis when there is high clinical suspicion and low perceived risk of bleeding. It is also critical to determine if any therapeutic approach beyond anticoagulation should be considered. This is perhaps the most vexing area in acute PE, which testing to do once the diagnosis is made and how this will influence our treatment plan. There are several parameters that can be examined to determine if more aggressive therapy should be considered. Vital signs and their trends are critical. While blood pressure serves to differentiate intermediate- from high-risk PE, the risk categories for acute PE (i.e., low-risk, intermediate-low risk, intermediate-high-risk, and high-risk) are heterogeneous and classification does not always specifically guide therapy. I have always believed, for example, that heart rate can serve as a very useful guide to the level of aggressiveness needed for acute PE. Naturally, drugs and age may affect the integrity of the conduction system, but a heart rate of 130 beats/minute defines a patient who is maximizing his/her ability to compensate, while a heart rate less than 100, in the absence of a negative chronotropic agent, is comforting—this simple measurement, especially with a few hours of trending, may aid substantially in therapeutic decisions. Drs. Triantafyllou, O’Corragain, Rivera-Lebron, and Rali, have very superbly outlined for us the general concepts and complexities of risk stratification including an algorithmic approach. Included in risk stratification is an analysis of right ventricular size and function to better assess if a patient is compensating adequately. The transthoracic echocardiogram has become an integral part of this process. Death from acute PE is from right ventricular failure. The echocardiography offers insight into how well the right ventricle is holding up, which can impact the therapeutic approach. Drs. Singh and Lewis from Los Angeles have provided an excellent update on right ventricular physiology and pathophysiology as well as the echocardiographic parameters that are most critical in clinical decision-making in acute PE. They also offer insight into novel imaging parameters that are being explored.
A novel concept is that of the PE response team which has taken off in the United States and is making its way around the world. This multidisciplinary approach to acute PE has proven a rapid means by which to assist the emergency department provider, the hospitalist, or any other clinician faced with suspected or proven acute PE. Dr. Channick from Los Angeles has provided a very insightful look at this rapid deployment team concept that perhaps might ultimately help reduce morbidity and mortality in acute PE. It certainly reduces clinician, and perhaps patient, anxiety! While standard therapy for acute PE usually initially includes parenteral anticoagulation, there have been major advances in oral anticoagulation. Drs. Stevens and McFadyen from Victoria, Australia, and Dr. Chan from Ontario, Canada, present for us an outstanding overview of several key areas in VTE including modern treatment approaches utilizing the direct oral anticoagulants (DOACs) and therapies that are being critically evaluated for potential future use. Drs. Dobesh, Kernan, and Lueshen from Nebraska very nicely complement this work by exploring other important areas involving these new drugs in obesity, renal insufficiency, and other special populations that clinicians must frequently face. This treatise addresses common problems that the average clinician does not often understand. The DOACs have simplified outpatient therapy for low-risk PE as well as facilitated both short- and long-term therapy.
As suggested earlier, we are often faced with patients who need more aggressive therapy than simply anticoagulation. Drs. Todoran and Petkovich from South Carolina has given us an excellent update on both systemic thrombolysis and catheter-directed approaches, and addresses the more difficult question of how to approach intermediate-risk patients in this regard. Subsequently, Drs. Murray, Zapata, and Keeling from Atlanta offer us a critical approach to when and how acute PE necessitates surgical embolectomy and the use of extracorporeal membrane oxygenation. Treatment considerations do not end at hospital discharge, and another form of risk stratification is necessary as the clinician determines the need for further testing as well as duration of anticoagulation. Among the key but controversial risk factors which help determine duration and intensity of therapy is testing for thrombophilic disorders. These clotting abnormalities, their genetics, and their impact on therapy are thoroughly reviewed by Drs. Gaddh and Rosovsky from Atlanta and Boston, respectively. The recognition of the major chronic sequela of acute PE (i.e., chronic thromboembolic pulmonary hypertension [CTEPH]) requires substantial expertise as does management of this entity. Our colleagues Drs. Boon, Huisman, and Klok from Leiden, in the Netherlands, offer a detailed look at post-PE dyspnea and CTEPH.
There are certain areas of medicine which require particular expertise and VTE in pregnancy is a perfect example. Dr. Bates from Ontario, Canada, has presented an exceptional overview of the complexities of acute VTE in the pregnant patient. Our penultimate article is one often not given the attention it deserves. New data continue to surface regarding prevention of acute VTE in the acutely ill medical patient. Drs. Macdougall and Spyropoulos offer an excellent approach to this exceptionally common clinical scenario—the medically ill are at substantial risk for acute VTE and remain at risk after hospital discharge. Finally, Dr. Samuel Berkman, a very experienced hematologist and thrombosis expert, and I have together presented information on the prothrombotic entity of COVID-19 infection predisposing to the development of acute VTE, an area in which data continue to accumulate.
In summary, the reader is offered an overview of the continuously evolving field of VTE. We should strive to continue to expand the evidence base so that we can offer our patients the most advanced and evidence-based care. I thank these outstanding experts for this compilation of superb treatises, and also Dr. Lynch and his staff for organizing this work and for the opportunity to present it to you. Finally, we must take a moment to thank Dr. Lynch for his decades of dedication to the Seminars in Respiratory and Critical Care Medicine. These volumes have offered outstanding guidance for physicians who face difficult clinical dilemmas. Often, level 1A evidence is lacking and expert opinion becomes critical in decision-making.
Dr. Lynch, thank you for offering this tremendous resource to so many clinicians around the world! The impact of this journal under your watch cannot be underestimated.
30 March 2021 (online)
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