Semin Respir Crit Care Med 2017; 38(01): 001-002
DOI: 10.1055/s-0036-1597554
Preface
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Controversies and Evolving Concepts in Acute Pulmonary Embolism

Victor F. Tapson
1   Division of Pulmonary and Critical Care, Venous Thromboembolism and Pulmonary Vascular Disease Research Program, Cedars-Sinai Medical Center, Clinical Research for the Women's Guild Lung Institute, Los Angeles, California
,
David Jimenez
2   Department of Respiratory, Venous Thromboembolism Research Program, Universidad de Alcala, Madrid, Spain
› Author Affiliations
Further Information

Publication History

Publication Date:
16 February 2017 (online)

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Victor F. Tapson, MD
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David Jimenez, MD, PhD, FCCP

Acute pulmonary embolism (PE) continues to be a major cause of death worldwide. It is the most common cause of death from vascular disease after coronary disease and stroke and is the leading preventable cause of death in hospitalized patients. A timely diagnosis remains critical but can be hindered by the often silent nature of deep venous thrombosis (DVT) and the unavoidable and unpredictable sudden death that occurs from PE in some patients. The clear benefit of anticoagulation for acute venous thromboembolism (VTE) has been realized for decades.

We are in the midst of a new era in VTE with novel therapeutic agents, specific anticoagulant reversal agents, and novel clot extraction and dissolution techniques. The accompanying clinical trial data are quite robust in some areas and less convincing in others. As is often the case, a solid evidence base supporting new promising technologies is lagging behind our enthusiasm to use them, rendering expert opinion as well as carefully planned randomized clinical trials even more crucial. Thus, it would appear timely to offer a Seminar in Respiratory and Critical Care Medicine on the topic of acute PE. The topics offered in this issue are presented by experts in acute VTE from around the world.

While the approach to acute DVT and PE certainly overlap, in this issue, we will focus a bit more on patients presenting with acute PE. We start with an outstanding review of the approach to suspected acute PE with a focus on the use of clinical prediction rules by Dr. Righini and colleagues. These experts emphasize that such prediction rules should be encouraged, but derived and validated following strict methodological standards.

The novel direct oral anticoagulants (DOACs) recently introduced have proven at least as effective as the vitamin K antagonists and generally safer with regard to bleeding. For patients treated with these new anticoagulants, therapy is simpler, does not require monitoring, and is fraught with far fewer potential drug interactions. Dr. Cohen and associates offer a superb review of the available data to guide the practicing clinician. We asked whether warfarin was dead, and they provided a detailed response. With increasing use of the DOACs, questions have arisen regarding the lack of reversibility of these agents and now we have some answers. While bleeding is generally successfully addressed without reversing anticoagulation, there are clearly situations in which rapid reversal would be ideal. Dr. Weitz has presented an insightful overview on the available data and what is on the horizon and how and when clinicians might consider their use.

Once the diagnosis of acute PE is made and anticoagulation is initiated, there are several parameters that can be examined to determine if additional therapy should be considered. Vital signs and their trends are critical to focus on. Right ventricular size and function have been used to assess severity of acute PE and are thus instrumental in classifying PE severity. The simplified Pulmonary Embolism Severity Index, which includes three physiological parameters, has been extensively studied as have biomarkers including troponin and brain natriuretic peptide. Drs. Jimenez and Yusen offer a logical approach to risk stratification and how it should guide clinicians. The echocardiogram has become an integral part of this process. Patients who die from acute PE die from right ventricular failure. The echocardiogram offers insight into how well the right ventricle is holding up, which can impact on the therapeutic approach. Drs. Dahhan and Rajagopal have provided an excellent review of the key echocardiographic parameters that are most useful to clinicians and some novel parameters that are being explored.

When patients with PE are severely hemodynamically compromised, that is, hypotensive, we need to be aggressive. We have known for decades that systemic thrombolytic therapy offers rapid clot dissolution but also that the risk of major bleeding including intracranial hemorrhage is significantly higher than with anticoagulation alone. Should we be pursuing more than anticoagulation therapy in the majority of patients with high-risk (massive) PE as well as intermediate-risk patients? Should we treat with a reduced dose of systemic thrombolytic therapy? The approach is not always intuitive when faced with these scenarios. Drs. Konstantinides and Barco walk us through the data, including the landmark PEITHO (Pulmonary Embolism Thrombolysis) trial, offering their expertise with regard to the use of systemic thrombolytic therapy. They emphasize that ongoing and planned studies focused on reduced dosages of intravenous thrombolytic agents and on pharmacomechanical catheter-directed reperfusion techniques could be promising with regard to efficacy and minimizing the bleeding risk associated with full-dose systemic thrombolysis.

Occasionally, critically ill patients with massive PE fail the most aggressive therapy or have absolute contraindications. Extracorporeal membrane oxygenation has been used in carefully selected patients. Drs. Weinberg and Ramzy have provided us an excellent review of the technique and of the available literature, offering recommendations for patient selection.

There has been an exponential increase in interest in more aggressive treatment approaches with novel catheter-based interventions for clot extraction and dissolution and these have been accompanied by an appropriate focus on risk stratification. While there are randomized trial data with catheter-facilitated therapy, such data are few and far between. Furthermore, the resources and expertise are not available at every hospital. The available techniques along with the evidence base are discussed and general guidelines for use of these new approaches are presented. With the advent of these new options, the need has arisen for expert multidisciplinary guidance. The Pulmonary Embolism Response Team (PERT) concept has evolved as a result, and Drs. Rodriguez-Lopez and Channick from Massachusetts General Hospital, the birthplace of the PERT concept, offer their expert views of how a multidisciplinary team can facilitate and expedite care in the setting of acute PE.

Vena cava filters remain controversial. While consensus statements have offered guidelines for their use, clinicians often encounter situations in which there is inadequate evidence to support their use yet placement may seem appropriate. It still appears that too few filters are removed. Drs. Moriarty and colleagues have presented a superb overview of this topic including information on progress with novel filter designs.

Finally, once the dust settles and the patient with acute PE presents to clinic for follow-up, decisions must be made with regard to duration of anticoagulation. Included in this decision process is whether evaluation for known thrombophilic disorders is necessary, and if so, what testing is appropriate. Was the PE event provoked or unprovoked? Or, did the timing of an apparent trigger seem causative but still relatively unimpressive, such as a short plane flight or bus ride? Should we use prediction models and/or D-dimer testing to aid in determining treatment duration? Dr. Becattini and our colleagues from Italy thoroughly address the issues of treatment duration, and Dr. Stevens and Ansell complete our issue with a detailed discussion of the thrombophilic disorders taking into account the various scenarios that require consideration. They indicate that new models that incorporate multiple genetic and clinical markers may improve the utility of testing, but that these approaches await further research.

In summary, this issue is a compilation of outstanding treatises by world experts, offering the reader an overview of a continuously evolving field. Our goal should be to continue to expand the evidence base so that we can offer our patients superlative care. Future research is critical. We thank these outstanding authors for their tremendous efforts and also thank Dr. Lynch and his staff for organizing this work and for the opportunity to present it to you.