Pulmonary embolism natural history, complications and prognosis

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Editor(s)-In-Chief:C. Michael Gibson, M.S., M.D. [1], The APEX Trial Investigators; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Pulmonary embolism can be acutely complicated by the development of cardiogenic shock, pulseless electrical activity and sudden cardiac death and chronically by the development of pulmonary hypertension. The medical management of pulmonary embolism often requires the administration of potent parenteral anticoagulants and fibrinolytics and massive bleeding can be a complication of their administration. If left untreated almost one-third of patients with pulmonary embolism die, typically from recurrent pulmonary embolism. However, with prompt diagnosis and treatment, the mortality rate is approximately 2–8%. The true mortality associated with pulmonary embolism may be underestimated as two-thirds of all pulmonary embolism cases are diagnosed by autopsy.

Complications

Acute Complications

Chronic Complications

Complications of Firbrinolytic Therapy for Pulmonary Embolism[2]

  • Severe bleeding can occur as a complication of fibrinolytic treatment:

Prognosis

If left untreated, almost one-third of the patients die, typically from recurrent PE. However, with prompt diagnosis and treatment, the mortality rate is approximately 2–8%. Unfortunately, two-thirds of all PE cases are diagnosed by autopsy. [3] Pulmonary embolism causes death in approximately 16% of hospitalized patients.

A 26% mortality rate associated with untreated pulmonary embolism is often cited based upon a trial published in 1960 by Barrit and Jordan[4] which compared anti-coagulation against placebo for the management of pulmonary embolism. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo controlled trial ever to examine the efficacy of anticoagulants in the treatment of pulmonary embolism. The results of this were so convincing that the trial has not been repeated. On the other hand, the reported mortality rate of 26% in the placebo group may underestimate the true mortality insofar as the sensitivity and specificity of diagnostic technology in 1957 may have only allowed the detection of massive pulmonary emboli.

Risk Stratification in Assessing Prognosis

The prognosis in a patient with pulmonary embolism depends upon:

  • The extent of the pulmonary vasculature that is occluded
  • Co-existence of other medical conditions (i.e. the patient's comorbidities)

Clinical correlates of mortality among patients with pulmonary embolism are listed below.

Hemodynamic Status

Observational studies such as the International Co-operative Pulmonary Embolism Registry (ICOPER) and the Management and Prognosis in Pulmonary Embolism Trial (MAPPET) have shown that shock and hypotension are principal high risk markers of early death in acute PE.[5] The MAPPET study demonstrated that systemic shock was associated with mortality of 24.5% where as hypotension (but not shock) was associated with the mortality of 15.2%.

A post-hoc analysis of the ICOPER study demonstrated that the 90-day all-cause mortality rate was 52.4% (95% CI,43.3–62.1%) among patients with a systolic blood pressure less than 90 mm Hg compared to 14.7% (95% CI, 13.3–16.2%) among patients with a normal blood pressure.[6]

The PESI (Pulmonary Embolism Severity Index) study demonstrated that hypotension (blood pressure <100 mm Hg) is associated with a mortality of nearly 50%. [7]

Markers of Right Ventricular Dysfunction (RVD) [8]

The presence of right ventricular dysfunction (RVD) on echocardiography has been associated with a higher mortality in the setting of pulmonary embolism.

Association of RV Dysfunction (RVD) on Echocardiography With Mortality in Pulmonary Embolism
Study Year Patients (n) Blood pressure Echocardiographic criteria RVD(present) vs. RVD(absent): Mortality percentage(%)
Goldhaber et al.[9] 1993 101 Normotensive RV hypokinesis and dilatation 4.3% vs. 0%
Ribeiro et al. [10] 1997 126 Normotensive and hypotensive RVD 12.8% vs. 0%
Kasper et al.[11] 1997 317 Normotensive and hypotensive RV >30 mm or TI >2.8 m/s 13% vs. 0.9%
Grifoni et al.[12] 2000 162 BP ≥ 100 mmHg Atleast one of the following
  • RV >30 mm or RV/LV >1
  • Paradox septal systolic motion
  • AcT <90 ms or TIPG >30 mmHg
4.6% vs. 0%
Kucher et al.[13] 2005 1035 BP ≤ 90 mmHg RVD 16.3% vs. 9.4%

Abbreviations Used: RV , right ventricle; TI, tricuspid insufficiency; LV, left ventricle; AcT, ACceleration Time of right ventricular ejection; TIPG, tricuspid insufficiency peak gradient.

Brain Natriuretic Peptide

In patients with a pulmonary embolism, elevated plasma levels of natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) have been associated with higher mortality.[14] Levels of N-terminal pro-brain natriuretic peptide greater than 500 ng/L serve as an indicator of the burden of PE and are associated with death.[15]

Serum Troponin

Elevated serum troponin levels are associated with an increased risk of death among pulmonary embolism patients. The elevation of troponin in patients with a massive pulmonary embolism does not reflect epicadial coronary artery disease but rather transmural RV infarctions on autopsy.[16] [17]

Hyponatremia

Hyponatremia at the time of presentation is associated with increased mortality and hospital readmission

Electrocardiographic Abnormalities

The electrocardiographic findings in pulmonary embolism can provide prognostic information (click here to read more). EKG findings that are associated with a poor prognosis include:[18]

  1. Atrial arrhythmias
  2. Right bundle branch block
  3. Q-waves in the inferior leads
  4. Precordial T-wave inversion and ST-segment changes.
  5. Development of a QR wave in lead V1 is identified as an independent risk factor for an adverse prognosis.[19]

ESC 2008 Guidelines for Prognostic Assessment (DO NOT EDIT)[20]

Class I
"1. Initial risk stratification of suspected and/or confirmed PE based on the presence of shock and hypotension is recommended to distinguish between patients with high and non-high-risk of PE-related early mortality. (Level of Evidence: B) "
Class II
"1. In non-high-risk PE patients, further stratification to an intermediate- or low-risk PE subgroup based on the presence of imaging or biochemical markers of RVD and myocardial injury should be considered.(Level of Evidence: B) "

References

  1. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) : The Lancet. Retrieved on 2012-10-07.
  2. Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism. Retrieved on 2012-10-06.
  3. American Heart Association. (2007). Venous Thromboembolism & Pulmonary Embolism - Statistical Fact Sheet: 2007 Update. Retreived from http://stopdvt.org/Documents/AMA%20Fact%20Sheet%20Current%20Research.pdf
  4. (1960) "Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.". Lancet 1: 1309–1312. PMID 13797091.
  5. Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD et al. (1997). "Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry.". J Am Coll Cardiol 30 (5): 1165-71. PMID 9350909.
  6. Kucher N, Rossi E, De Rosa M, Goldhaber SZ (2006). "Massive pulmonary embolism.". Circulation 113 (4): 577-82. doi:10.1161/CIRCULATIONAHA.105.592592. PMID 16432055.
  7. Donzé J, Le Gal G, Fine MJ, Roy PM, Sanchez O, Verschuren F et al. (2008). "Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism.". Thromb Haemost 100 (5): 943-8. PMID 18989542.
  8. Konstantinides S (2005). "Pulmonary embolism: impact of right ventricular dysfunction.". Curr Opin Cardiol 20 (6): 496-501. PMID 16234620.
  9. Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL et al. (1993). "Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion.". Lancet 341 (8844): 507-11. PMID 8094768.
  10. Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L (1997). "Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate.". Am Heart J 134 (3): 479-87. PMID 9327706.
  11. Kasper W, Konstantinides S, Geibel A, Tiede N, Krause T, Just H (1997). "Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism.". Heart 77 (4): 346-9. PMID 9155614.
  12. Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G et al. (2000). "Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction.". Circulation 101 (24): 2817-22. PMID 10859287.
  13. Kucher N, Rossi E, De Rosa M, Goldhaber SZ (2005). "Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher.". Arch Intern Med 165 (15): 1777-81. doi:10.1001/archinte.165.15.1777. PMID 16087827.
  14. Cavallazzi R, Nair A, Vasu T, Marik PE (2008). "Natriuretic peptides in acute pulmonary embolism: a systematic review.". Intensive Care Med 34 (12): 2147-56. doi:10.1007/s00134-008-1214-5. PMID 18626627.
  15. Alonso-Martínez JL, Urbieta-Echezarreta M, Anniccherico-Sánchez FJ, Abínzano-Guillén ML, Garcia-Sanchotena JL (2009). "N-terminal pro-B-type natriuretic peptide predicts the burden of pulmonary embolism.". Am J Med Sci 337 (2): 88-92. doi:10.1097/MAJ.0b013e318182d33e. PMID 19214022.
  16. Becattini C, Vedovati MC, Agnelli G (2007). "Prognostic value of troponins in acute pulmonary embolism: a meta-analysis.". Circulation 116 (4): 427-33. doi:10.1161/CIRCULATIONAHA.106.680421. PMID 17606843.
  17. Jiménez D, Uresandi F, Otero R, Lobo JL, Monreal M, Martí D et al. (2009). "Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis.". Chest 136 (4): 974-82. doi:10.1378/chest.09-0608. PMID 19465511.
  18. Ferrari E, Imbert A, Chevalier T, Mihoubi A, Morand P, Baudouy M (1997). "The ECG in pulmonary embolism. Predictive value of negative T waves in precordial leads--80 case reports.". Chest 111 (3): 537-43. PMID 9118684.
  19. Kucher N, Walpoth N, Wustmann K, Noveanu M, Gertsch M (June 2003). "QR in V1--an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism". European Heart Journal 24 (12): 1113–9. PMID 12804925. Retrieved on 2011-12-05.
  20. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP (September 2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)". Eur. Heart J. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870. Retrieved on 2011-12-07.

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