Acute pulmonary embolism (PE) is still one of the most feared diagnoses in the United States, causing the deaths of 300,000 Americans per year,1 many of whom were previously healthy. Until relatively recently, our medical toolbox has been limited to anticoagulation, intravenous lytics, and the occasional surgical embolectomy. The last two were used sparingly because of high major bleeding rates and anatomic limitations, respectively. Many clinicians would anticoagulate and anxiously offer supportive care, hoping that the patient would autolyse and not spiral toward hemodynamic instability, cardiac arrest, and death.

THE EVOLVING TREATMENT LANDSCAPE

The question posed to the medical community during the past several decades is how to improve on these subpar statistics, with mortality rates ranging from 3% to 10% for submassive PEs and 15% to 65% for massive PEs. The first challenge has been to diagnose PE more rapidly and accurately. Clinically, PE can be elusive, often considered only after a “clean” cardiac catheterization, a negative endoscopy, or an unhelpful trial of bronchodilators. Medical training has emphasized always keeping PE in the differential for tachycardia, chest pain, and abnormal cardiac enzymes, among other signs, symptoms, and laboratory values. Computed tomographic angiography has revolutionized the diagnosis of PE, effectively replacing ventilation-perfusion scanning and pulmonary angiography.

Beyond improving the rapidity and accuracy of diagnosis, technical and pharmaceutical advances and provocative data have made the toolbox larger. Although the standard intravenous alteplase dose is 100 mg, administering only 50 mg may have the same therapeutic benefit with less risk.2 Catheter-based techniques, including mechanical fragmentation, thrombus aspiration, intrathrombus lytic administration, and prolonged catheter-directed infusion, may play a significant role in a subset of PE patients.3 For the patients in extremis, improved outcomes with surgical embolectomy and extracorporeal membrane oxygenation may rescue those previously considered to have little to no chance of survival.

DEVELOPING A TEAM-BASED APPROACH

Managing these patients requires a coordinated effort among different subspecialties. The essential lesson for interventionists is to build or integrate into a team. For example, at our institution, we have built a PE acute care (PEAC) team, which consists of a pulmonary/critical care attending physician (Dr. Friedman), a cardiology attending physician (Dr. Horowitz), an interventional radiology attending physician (Dr. Sista), and a cardiothoracic surgeon (Dr. Salemi). There were several impetuses for creating this team; for years, there was a lack of knowledge of potential endovascular interventions among critical care attending physicians. It was a successful endovascular case that catalyzed the creation of our team (Figures 1 and 2). Additionally, there were scattered stories of patients with hemodynamically significant pulmonary emboli who were not receiving appropriate triage and support. Accordingly, the mission of the PEAC team is to rapidly identify patients who require treatment escalation, determine which thromboreductive strategy is most appropriate, and implement that strategy.

SUMMARY OF THE PUBLISHED LITERATURE

Our first step in forming the PEAC team was to become familiar with the PE literature. Older studies, such as ICOPER and MAPPET, provided important epidemiological data.4,5 The American Heart Association (AHA) and American College of Chest Physicians guidance documents6,7 offered recommendations based on the level and strength of existing data, although they had to be placed in the proper context given the relative paucity of level 1 evidence surrounding treatment escalation. The AHA guidance document stratified pulmonary emboli into massive, submassive, and low risk. Familiarity with these strata, their respective mortality risks, and the treatment options for each allowed us to develop internal algorithms for each type of PE (Figure 3).

Although data for massive PE are limited to retrospective analyses and meta-analyses (Kuo et al3 authored the most extensive meta-analysis on catheter-based techniques in 2009, showing excellent global results with catheter-based techniques for the treatment of massive PE), randomized controlled data are quickly emerging for submassive PE. There are now four significant prospective randomized controlled trials comparing intravenous thrombolysis with anticoagulation alone in the setting of submassive PE, including the recent PEITHO, TOPCOAT, and MOPETT trials.2,8-10 The overall conclusion from these trials is that systemic thrombolysis improves short- and medium-term outcomes, although major bleeding did occur more frequently in the systemic lytic group in the largest of these trials (PEITHO).

The ULTIMA study, which was presented at this year's ACC scientific sessions, was a randomized controlled trial looking at ultrasound-assisted, catheter-directed thrombolysis in the setting of submassive PE.11 The PERFECT registry and SEATTLE II studies will add to the existing knowledge on catheter-directed techniques in the setting of submassive PE.

INTEGRATING THE TEAM INTO YOUR HOSPITAL SYSTEM

Once our internal education was complete and initial algorithms were drafted, the next step was disseminating our purpose and presence to our colleagues. Thus, we have arranged lectures with the internal medicine house staff, the emergency department, the critical care attending physicians, and the anesthesiologists. We have created a PEAC pager, and we are in the process of distributing pens decorated with our logo and pager number. Ultimately, we aim to either develop a new service line or become integrated into one of the hospital's existing service lines.

With our efforts have come cases. Some patients have been treated with systemic tissue plasminogen activator, whereas others have been routed to catheter- directed techniques. The team meets on a monthly basis to review our cases and their outcomes and to revise our algorithms as necessary.

In the interventional suite, we have had a number of successes (Figure 4); however, we have also had a few failures. The failures have not been technical; in retrospect, they were related to patient selection. The main lesson we have learned is how complicated general anesthesia can be. Physiologically, anesthesia induction increases pulmonary vascular resistance, which, in combination with positive airway pressure, decreases venous return in an already compromised right-sided circulation.

In one unfortunate case, a patient was coded three times after intubation before the procedure began. If intubation is at all necessary, either because of patient agitation or cardiopulmonary collapse, we have agreed that the patient should go straight to the operating room under the care of cardiac anesthesia and Dr. Salemi, who has had excellent outcomes during the past several years. In this setting, rapid heroic measures, such as extracorporeal membrane oxygenation, can be performed in conjunction with embolectomy.

POSTTREATMENT FOLLOW-UP

Although we are mainly focused on the acute setting, we have realized the importance of following these patients longitudinally. A growing body of evidence suggests that patients who survive hemodynamically significant PEs may go on to develop symptoms, signs, and echocardiographic evidence of pulmonary hypertension—perhaps the pulmonary equivalent to the postthrombotic syndrome seen in patients with lower extremity deep venous thrombosis.12,13 In these studies, the manifestations have been systolic pulmonary pressures > 40 mm Hg, continued right heart dysfunction, and poor 6-minute walk times, along with persistent dyspnea on exertion. Therefore, we arrange follow-up visits at 3 and 6 months to assess for pulmonary hypertension. Each visit consists of obtaining a repeat echocardiogram and documenting any worrisome symptoms. We will also soon incorporate a 6-minute walk test. From these follow-ups, we hope to correlate the initial treatment with the presence or absence of pulmonary hypertension.

CONCLUSION

We have found acute PE to be a fascinating and humbling disease. The physiologic complexity is daunting and requires advanced care from critical care physicians, cardiologists, interventionists, cardiothoracic surgeons, and anesthesiologists. We are relatively early in our attempts to formalize a PE acute care team, but we believe that such a collaboration has educated us and our colleagues and will ultimately lead to better patient care.

Akhilesh K. Sista, MD, is Assistant Professor, Division of Interventional Radiology, Weill Cornell Medical College in New York, New York. He stated that he has no financial interests related to this article. Dr. Sista may be reached at aks9010@med.cornell.edu.

Oren A. Friedman, MD, is Assistant Professor, Division of Pulmonary Critical Care, Weill Cornell Medical College in New York, New York. He stated that he has no financial interests related to this article.

James M. Horowitz, MD, is Assistant Professor, Division of Cardiology, Weill Cornell Medical College in New York, New York. He stated that he has no financial interests related to this article.

Arash Salemi, MD, is Associate Professor, Department of Cardiothoracic Surgery, Weill Cornell Medical College in New York, New York. He stated that he has no financial interests related to this article.

  1. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008;358:1037-1052.
  2. Sharifi M, Bay C, Skrocki L, et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” trial). Am J Cardiol. 2013;111:273-277.
  3. Kuo WT, Gould MK, Louie JD, et al. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques. J Vasc Interv Radiol. 2009;20;1431-1440.
  4. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:1386-1389.
  5. Kasper W, Konstantinides S, Geibel A, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol. 1997;30:1165-1171.
  6. Jaff MR, McMurtry S, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123:1788-1830.
  7. Kearon C, Akl EA, Comerota AJ. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(suppl):e419S-e494S.
  8. Konstantinides SV, Meyer G, Lang I, et al. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury: rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J. 2012;163:33-38.
  9. Konstantinides S, Geibel A, Heusel G, et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347:1143-1150.
  10. Konstantinides S. Randomized trial of tenecteplase to treat severe submassive pulmonary embolism. Presented at the 2013 AHA scientific sessions.
  11. Kucher N. The ULTIMA trial. Presented at the 2013 American College of Cardiology meeting; March 9–11, 2013; San Francisco, CA.
  12. Kline JA, Steuerwald MT, Marchick MR, et al. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest. 2009;136:1202-1210.
  13. Stevinson BG, Hernandez-Nino J, Rose G, Kline JA. Echocardiographic and functional cardiopulmonary problems 6 months after first-time pulmonary embolism in previously healthy patients. Eur Heart J. 2007;28:2517-2524.