Pulmonary embolism natural history, complications and prognosis
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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
The natural history of pulmonary embolism and deep vein thrombosis are intertwined.[1].
Natural History
Complications
- Heart failure or shock
- Palpitations
- Pulmonary hypertension
- Severe dyspnea
- Severe bleeding (usually a complication of treatment)
- Sudden death
- Chronic thromboembolic hypertension. (rare - 1%)[2]
Notable people who died from pulmonary emboli are Rapper Heavy D [3] and NBC correspondent David Bloom [4]. Tennis player Serena Williams [5], suffered an attack of PE, but was rescued on time.
- Complications of thrombolytic therapy[3]
- Major hemorrhage - 10%
- Non major hemorrhage - 20%
- Intracranial hemorrhage - 0.5%
Prognosis
The mortality rate due to untreated PE was found to be 26%. This rate stems from a trial published in 1960 by Barrit and Jordan[4] which compared anti-coagulation 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 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 be an understatement because the technology in 1957 may have only detected severe PEs. 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. [5] PE causes death in approximately 16% of hospitalized patients.
Prognosis depends upon:
- The amount of lung that is affected
- Co-existence of other medical conditions (Eg. chronic embolization to the lung can lead to pulmonary hypertension).
Prognostic Assessment
Factors predicting mortality in pulmonary embolism patients are:
- Clinical assessment of Hemodynamic status
Observational studies such as the International COoperative 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.[6]
Post trial 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 a systolic blood pressure less than 90 mmHg compared to 14.7% (95% CI, 13.3–16.2%) in patients with a normal blood pressure.[7]
According to the MAPPET study, systemic hypotension seems to carry a slightly lower risk compared to shock (in-hospital all-cause mortality, 15.2 vs. 24.5%, respectively).
According to the 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. [9]
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.[10] | 1993 | 101 | Normotensive | RV hypokinesis and dilatation | 4.3% vs. 0% |
| Ribeiro et al. [11] | 1997 | 126 | Normotensive and hypotensive | RVD | 12.8% vs. 0% |
| Kasper et al.[12] | 1997 | 317 | Normotensive and hypotensive | RV >30 mm or TI >2.8 m/s | 13% vs. 0.9% |
| Grifoni et al.[13] | 2000 | 162 | BP ≥ 100 mmHg | Atleast one of the following
|
4.6% vs. 0% |
| Kucher et al.[14] | 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.
- Markers of Myocardial Injury
- 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.[15]
A separate study involving 93 pulmonary embolism patients concluded that levels of N-terminal pro-brain natriuretic peptide greater than 500 ng/L could serve as an indicator of the burden of PE and perhaps as a predictor of death.[16]
- Serum troponins
Elevated serum troponin levels are associated with an increased risk of death in PE patients. Patients who died of massive PE were found to have transmural RV infarctions on autopsy, despite having patent coronary arteries.[17] [18]
- Additional Risk Markers
Hyponatremia at the time of presentation is associated with
- Increased mortality
- Hospital readmission
There is controversy regarding the treatment of small subsegmental PE,[19] and some evidence exists that patients with subsegmental PEs may do well without treatment.[20][21]
ECG findings can also help in assessing the prognosis. Please click here to read more.
ESC 2008 Guidelines for Prognostic Assessment (DO NOT EDIT)
| Class I |
| "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 |
| "'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) " |
Guidelines Resources
- Guidelines on the diagnosis and management of acute pulmonary embolism.[1]
References
- ↑ 1.0 1.1 1.2 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.
- ↑ "Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) : The Lancet". Retrieved 2012-10-07.
- ↑ "Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism". Retrieved 2012-10-06.
- ↑ "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)
- ↑ 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
- ↑ 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.
- ↑ 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.
- ↑ Konstantinides S (2005). "Pulmonary embolism: impact of right ventricular dysfunction". Curr Opin Cardiol. 20 (6): 496–501. PMID 16234620.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Perrier A, Bounameaux H (2006). "Accuracy or outcome in suspected pulmonary embolism". N Engl J Med. 354 (22): 2383–5. PMID 16738276.
- ↑ 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.