Pulmonary embolism natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editors-in-Chief: Ujjwal Rastogi, MBBS [2]

Overview

Pulmonary embolism in mostly a a consequence of Deep vein thrombosis, thus natural history of VTE should be considered as a whole instead of separately looking at DVT and PE[1].

Natural History

Approximately one-third of patients with pulmonary embolism who are not treated will die. without treatment, usually from recurrent PE. However, with diagnosis and treatment, the mortality rate is only ~ 2 – 8%. Unfortunately, 2/3 of all cases of PE are not diagnosed untill autopsy.

Prognosis

Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan[2] which compared anticoagulation against placebo for the management of PE. 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 place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs.

Prognosis depends on:

  • The amount of lung that is affected
  • Co-existence of other medical conditions; chronic embolisation to the lung can lead to pulmonary hypertension.

Prognostic Assessment

Factors predicting mortality in pulmonary embolism patients are:

  • Clinical Assessment of Haemodynamic Status

Observational studies like International COoperative Pulmonary Embolism Registry (IOCPER) and Management and Prognosis in Pulmonary Embolism Trial (MAPPET)[3] have shown that Shock and hypotension are principal markers of high risk of early death in acute PE.

Post hoc analysis of ICOPER study data showed, that, the 90-day all-cause mortality rate was 52.4% (95% CI,43.3–62.1%) in patients with systolic blood pressure less than 90 mmHg compared with 14.7% (95% CI, 13.3–16.2%) in normotensive patients[4].

According to the MAPPET study, systemic hypotension, seems to carry a slightly lower risk compared with shock (in-hospital all-cause mortality, 15.2 vs. 24.5%, respectively).

According to PESI (Pulmonary Embolism Severity Index) trial, Hypotension (blood pressure <100 mm Hg) is a significant risk factor causing mortality in half of the patient group [6].

Trials reporting significance of RV dysfunction (RVD) in Pulmonary embolism (assessed by echocardiography)

Study Year Patients (n) Blood pressure Echocardiographic criteria RVD(present) vs. RVD(absent): Mortality percentage(%)
Goldhaber et al.[7] 1993 101 Normotensive RV hypokinesis and dilatation 4.3% vs. 0%
Ribeiro et al. [8] 1997 126 Normotensive and hypotensive RVD 12.8% vs. 0%
Kasper et al.[9] 1997 317 Normotensive and hypotensive RV >30 mm or TI >2.8 m/s 13% vs. 0.9%
Grifoni et al.[10] 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.[11] 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.

In patients with pulmonary embolism, elevated plasma levels of natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) have been associated with higher mortality[12].

In a study conducted in spain[13], where 93 pulmonary embolism patients were studied, It was proposed that the levels of N -terminal pro-brain natriuretic peptide greater than 500 ng/L could serve as indicator of the burden of PE and perhaps as a predictor of death.

Elevated serum troponin levels are associated with an increased risk of death in PE patients[14].

There is controversy over whether or not small subsegmental PEs need to be treated at all[15] and some evidence exists that patients with subsegmental PEs may do well without treatment.[16][17]

References

  1. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P; et al. (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.
  2. "Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial". Lancet. 1: 1309&ndash, 1312. 1960. PMID 13797091. Text " Barritt DW, Jorden SC " ignored (help)
  3. 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.
  4. 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.
  5. Konstantinides S (2005). "Pulmonary embolism: impact of right ventricular dysfunction". Curr Opin Cardiol. 20 (6): 496–501. PMID 16234620.
  6. 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.
  7. 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.
  8. 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.
  9. 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. PMC 484729. PMID 9155614.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F (2006). "Diagnosis and management of subsegmental pulmonary embolism". J Thromb Haemost. 4 (4): 724–31. PMID 16634736.
  16. Perrier A, Bounameaux H (2006). "Accuracy or outcome in suspected pulmonary embolism". N Engl J Med. 354 (22): 2383–5. PMID 16738276.
  17. Stein P, Fowler S, Goodman L, Gottschalk A, Hales C, Hull R, Leeper K, Popovich J, Quinn D, Sos T, Sostman H, Tapson V, Wakefield T, Weg J, Woodard P (2006). "Multidetector computed tomography for acute pulmonary embolism". N Engl J Med. 354 (22): 2317–27. PMID 16738268.

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