Pulmonary embolism natural history, complications and prognosis: Difference between revisions

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__NOTOC__
{| class="infobox" style="float:right;"
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| [[File:Siren.gif|30px|link=Pulmonary embolism resident survival guide]]|| <br> || <br>
| [[Pulmonary embolism resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
{{Pulmonary embolism}}
{{Pulmonary embolism}}
 
{{CMG}} {{ATI}}; {{AE}} {{Rim}}
{{CMG}}
'''Associate Editors-in-Chief:''' [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]


==Overview==
==Overview==
Pulmonary embolism is mostly 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<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=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). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870 }} </ref>.
Pulmonary embolism (PE) 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 PE 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 PE die, typically from recurrent PE.  However, with prompt diagnosis and treatment, the [[mortality rate]] is approximately 2–8%. The true mortality associated with PE may be underestimated as two-thirds of all PE cases are diagnosed by [[autopsy]].  Estimates suggest that 60,000-100,000 Americans die of [[VTE]], 10 to 30% of which will die within one month of diagnosis. Sudden death is the first [[symptom]] in about one-quarter (25%) of people who have a PE.  One-third (about 33%) of people with [[VTE]] will have a recurrence within 10 years.<ref>[http://www.cdc.gov/ncbddd/dvt/data.html CDC- Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) — Blood Clot Forming in a Vein]</ref><ref name="pmid20331949">{{cite journal| author=Beckman MG, Hooper WC, Critchley SE, Ortel TL| title=Venous thromboembolism: a public health concern. | journal=Am J Prev Med | year= 2010 | volume= 38 | issue= 4 Suppl | pages= S495-501 | pmid=20331949 | doi=10.1016/j.amepre.2009.12.017 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20331949 }} </ref>


==Natural History==
Subsegmental [[pulmonary emboli]] may<ref name="pmid20546118">{{cite journal| author=Carrier M, Righini M, Wells PS, Perrier A, Anderson DR, Rodger MA et al.| title=Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. | journal=J Thromb Haemost | year= 2010 | volume= 8 | issue= 8 | pages= 1716-22 | pmid=20546118 | doi=10.1111/j.1538-7836.2010.03938.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20546118  }} </ref> or may not<ref name="pmid23736701">{{cite journal| author=den Exter PL, van Es J, Klok FA, Kroft LJ, Kruip MJ, Kamphuisen PW et al.| title=Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. | journal=Blood | year= 2013 | volume= 122 | issue= 7 | pages= 1144-9; quiz 1329 | pmid=23736701 | doi=10.1182/blood-2013-04-497545 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23736701  }} </ref> have a favorable [[prognosis]].
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==
==Complications==
Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan<ref name="Barritt">{{cite journal | Barritt DW, Jorden SC | title=Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. | journal=[[The Lancet|Lancet]] | year=1960 | volume=1 | pages=1309&ndash;1312 | id=PMID 13797091 }}</ref> 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.
===Acute Complications===
*[[Atrial flutter]]
*[[Heart failure]] or [[shock]]
*[[Pulmonary hypertension]]
*[[Pulseless electrical activity]]
*[[Sudden cardiac death]]


Prognosis depend upon:
===Chronic Complications===
*The amount of lung that is affected
*[[Chronic]] [[thromboembolic]] [[hypertension]] (rare - 1%)<ref name="urlAcute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) : The Lancet">{{cite web |url=http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)07534-5/abstract |title=Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) : The Lancet |format= |work= |accessdate=2012-10-07}}</ref>
*Co-existence of other medical conditions (Eg. chronic embolisation to lung can lead to [[pulmonary hypertension]]).
*[[Pulmonary hypertension]]
*Recurrent [[pulmonary embolism]]


===Prognostic Assessment===
===Complications of Firbrinolytic Therapy for Pulmonary Embolism<ref name="urlThrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism">{{cite web |url=http://circ.ahajournals.org/content/110/6/744.abstract?sid=382ce1b3-7625-4ac5-9c41-d8da4ac70d41 |title=Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism |format= |work= |accessdate=2012-10-06}}</ref>===
'''Factors predicting mortality in pulmonary embolism patients are:'''
*Severe bleeding can occur as a complication of [[fibrinolytic]] treatment:
* '''Clinical assessment of Haemodynamic status'''
:* [[Major hemorrhage]] - 10%
Observational studies like International COoperative Pulmonary Embolism Registry (IOCPER) and Management and Prognosis in Pulmonary Embolism Trial (MAPPET) have shown that Shock and hypotension are principal markers of high risk of early death in acute PE.<ref name="pmid9350909">{{cite journal| author=Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD et al.| title=Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. | journal=J Am Coll Cardiol | year= 1997 | volume= 30 | issue= 5 | pages= 1165-71 | pmid=9350909 | doi= | pmc=| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9350909 }} </ref>
:* Non major [[hemorrhage]] - 20%
:* [[Intracranial hemorrhage]] - 0.5%


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<ref name="pmid16432055">{{cite journal| author=Kucher N, Rossi E, De Rosa M, Goldhaber SZ| title=Massive pulmonary embolism. | journal=Circulation | year= 2006 | volume= 113 | issue= 4 | pages= 577-82 |pmid=16432055 | doi=10.1161/CIRCULATIONAHA.105.592592 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16432055 }} </ref>.
==Prognosis==
===Pulmonary Embolism Severity Index (PESI) Score===
The Pulmonary Embolism Severity Index (PESI) score aims to stratify patients with PE into classes of increasing rate of mortality and adverse outcomes.<ref name="pmid16020800">{{cite journal| author=Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J et al.| title=Derivation and validation of a prognostic model for pulmonary embolism. | journal=Am J Respir Crit Care Med | year= 2005 | volume= 172 | issue= 8 | pages= 1041-6 | pmid=16020800 | doi=10.1164/rccm.200506-862OC | pmc=PMC2718410 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16020800 }} </ref>


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).
====Calculation of PESI Score====
* '''Markers of Right ventricular dysfunction [[RV dysfunction|(RVD)]] '''<ref name="pmid16234620">{{cite journal| author=Konstantinides S| title=Pulmonary embolism: impact of right ventricular dysfunction. | journal=Curr Opin Cardiol | year= 2005 | volume= 20 | issue= 6 | pages= 496-501 | pmid=16234620 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16234620  }} </ref>
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
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 <ref name="pmid18989542">{{cite journal| author=Donzé J, Le Gal G, Fine MJ, Roy PM, Sanchez O, Verschuren F et al.| title=Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism. | journal=Thromb Haemost | year= 2008 | volume= 100 | issue= 5 | pages= 943-8 | pmid=18989542 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18989542  }} </ref>.
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center |'''Age, per yr''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center | '''Age, in yr'''
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Male sex ||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |10
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |[[Cancer]] || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |30
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |[[Heart failure]] || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |10
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Chronic [[lung]] disease|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |10
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |[[Pulse]] ≥110 beat/min|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |20
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Systolic [[blood pressure]] <100 mmHg ||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |30
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |[[Respiratory rate]] ≥30/min || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |20
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |[[Temperature]] <36 ||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |20
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |[[Altered mental status]] || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |60
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Arterial [[oxygen saturation]] <90% || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |20
|}


'''Trials reporting significance of RV dysfunction (RVD) in Pulmonary embolism (assessed by echocardiography)'''
====Interpretation of PESI Score====
{| border="1"
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|+
! Study !! Year !! Patients (n) !! Blood pressure !! [[ Echocardiographic]] criteria !! RVD(present) vs. RVD(absent): Mortality percentage(%)
|-
|-
| Goldhaber et al.<ref name="pmid8094768">{{cite journal| author=Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL et al.| title=Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. | journal=Lancet | year= 1993 | volume= 341 | issue= 8844 | pages= 507-11 | pmid=8094768 | doi= | pmc= | url= }} </ref>
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center |'''Class''' ||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center | '''Score'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center |'''Class–specific 30-day mortality'''
| 1993
| 101
| Normotensive
| RV hypokinesis and dilatation
| 4.3% vs. 0%
|-
|-
| Ribeiro et al. <ref name="pmid9327706">{{cite journal| author=Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L| title=Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. | journal=Am Heart J | year= 1997 | volume= 134 | issue= 3 | pages= 479-87 | pmid=9327706 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9327706  }} </ref>
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Class I, very low risk ||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |≤65|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |1.1%
| 1997
| 126
| Normotensive and [[hypotensive]]
| [[RVD]]
| 12.8% vs. 0%
|-
|-
| Kasper et al.<ref name="pmid9155614">{{cite journal| author=Kasper W, Konstantinides S, Geibel A, Tiede N, Krause T, Just H| title=Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism. | journal=Heart | year= 1997 | volume= 77 | issue= 4 | pages= 346-9 | pmid=9155614 | doi= | pmc=PMC484729 | url= }} </ref>
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Class II, low risk || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |65-85|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |3.1%
| 1997
| 317
| Normotensive and [[hypotensive]]
| RV >30 mm or TI >2.8 m/s
| 13% vs. 0.9%
|-
|-
| Grifoni et al.<ref name="pmid10859287">{{cite journal| author=Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G et al.| title=Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. | journal=Circulation | year= 2000 | volume= 101 | issue= 24 | pages= 2817-22 | pmid=10859287 | doi= | pmc= | url= }} </ref>
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Class III, intermediate risk ||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |86-105||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |6.5%
| 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.<ref name="pmid16087827">{{cite journal| author=Kucher N, Rossi E, De Rosa M, Goldhaber SZ| title=Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher. | journal=Arch Intern Med | year= 2005 | volume= 165 | issue= 15 | pages= 1777-81 | pmid=16087827 | doi=10.1001/archinte.165.15.1777 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16087827  }} </ref>
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Class IV, high risk ||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |106-125||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |10.4%
| 2005
|-
| 1035
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |Class V, very high risk || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |>125 ||style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |24.5%
| 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'''
===HOPPE risk score===
*[[Brain natriuretic peptide]]
The HOPPE risk score contains<ref name="pmid28683900">{{cite journal| author=Subramanian M, Gopalan S, Ramadurai S, Arthur P, Prabhu MA, Thachathodiyl R et al.| title=Derivation and Validation of a Novel Prediction Model to Identify Low-Risk Patients With Acute Pulmonary Embolism. | journal=Am J Cardiol | year= 2017 | volume= 120 | issue= 4 | pages= 676-681 | pmid=28683900 | doi=10.1016/j.amjcard.2017.05.043 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28683900  }} </ref>:
* [[Heart rate]]
* PaO2 ([[arterial]] [[partial pressure]] of [[oxygen]])
* [[Systolic]] [[blood pressure]]
* [[Diastolic]] [[blood pressure]]
* [[Electrocardiographic]] score
 
The HOPPE has not been studied as extensively as PESI; however, initial study suggests it may prove more accurate.<ref name="pmid28683900">{{cite journal| author=Subramanian M, Gopalan S, Ramadurai S, Arthur P, Prabhu MA, Thachathodiyl R et al.| title=Derivation and Validation of a Novel Prediction Model to Identify Low-Risk Patients With Acute Pulmonary Embolism. | journal=Am J Cardiol | year= 2017 | volume= 120 | issue= 4 | pages= 676-681 | pmid=28683900 | doi=10.1016/j.amjcard.2017.05.043 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28683900  }} </ref>
 
===Hestia Clinical Decision Rule===
The Hestia Clinical Decision Rule can help guide the decision for [[hospitalization]].<ref name="pmid27030891">{{cite journal| author=den Exter PL, Zondag W, Klok FA, Brouwer RE, Dolsma J, Eijsvogel M et al.| title=Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial. | journal=Am J Respir Crit Care Med | year= 2016 | volume= 194 | issue= 8 | pages= 998-1006 | pmid=27030891 | doi=10.1164/rccm.201512-2494OC | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27030891  }} </ref>
 
===Hospitalization for VTE===
* During 2007–2009, an estimated annual average of 547,596 [[hospitalizations]] had a diagnosis of [[VTE]] for adults aged ≥18 years. Estimates for [[DVT]] and [[PE]] diagnoses were not mutually exclusive. An estimated annual average of 348,558 adult [[hospitalizations]] had a diagnosis of [[DVT]], and 277,549 adult [[hospitalizations]] had a diagnosis of [[PE]]. An estimated annual average of 78,511 adult hospitalizations (14% of overall [[VTE]] hospitalizations) had diagnoses of both [[DVT]] and [[PE]].<ref name=CDC2> [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6122a1.htm?s_cid=mm6122a1_w ] Hussain R. Yusuf, MD, James Tsai, MD, Hani K. Atrash, MD, Sheree Boulet, DrPH, Scott D. Grosse, PhD, Div of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, CDC. Venous Thromboembolism in Adult Hospitalizations — United States, 2007–2009</ref>


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<ref name="pmid18626627">{{cite journal| author=Cavallazzi R, Nair A, Vasu T, Marik PE| title=Natriuretic peptides in acute pulmonary embolism: a systematic review. | journal=Intensive Care Med | year= 2008 | volume= 34 | issue= 12 | pages= 2147-56 | pmid=18626627 | doi=10.1007/s00134-008-1214-5 | pmc= | url= }} </ref>.
* The estimated average annual number of [[hospitalizations]] with [[VTE]] was successively greater among older age groups: 54,034 for persons aged 18–39 years; 143,354 for persons aged 40–59 years; and 350,208 for persons aged ≥60 years. The estimated average annual number of hospitalizations with [[VTE]] was comparable for men (250,973) and women (296,623).<ref name=CDC2> [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6122a1.htm?s_cid=mm6122a1_w ] Hussain R. Yusuf, MD, James Tsai, MD, Hani K. Atrash, MD, Sheree Boulet, DrPH, Scott D. Grosse, PhD, Div of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, CDC. Venous Thromboembolism in Adult Hospitalizations — United States, 2007–2009</ref>  Shown below is an image depicting the estimated average annual number of hospitalization with a diagnosis of [[DVT]], [[PE]], or [[VTE]] by age and sex (image courtesy of CDC.gov<ref name=CDC2> [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6122a1.htm?s_cid=mm6122a1_w ] Hussain R. Yusuf, MD, James Tsai, MD, Hani K. Atrash, MD, Sheree Boulet, DrPH, Scott D. Grosse, PhD, Div of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, CDC. Venous Thromboembolism in Adult Hospitalizations — United States, 2007–2009</ref>).


A separate study involving 93 pulmonary embolism patients, concluded that the 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.<ref name="pmid19214022">{{cite journal| author=Alonso-Martínez JL, Urbieta-Echezarreta M, Anniccherico-Sánchez FJ, Abínzano-Guillén ML, Garcia-Sanchotena JL| title=N-terminal pro-B-type natriuretic peptide predicts the burden of pulmonary embolism. | journal=Am J Med Sci | year= 2009 | volume= 337 | issue= 2 | pages= 88-92 | pmid=19214022 |doi=10.1097/MAJ.0b013e318182d33e | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19214022  }} </ref>
[[File:Estimated average annual number of hospitalization VTE.gif]]
*Serum [[Troponin|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 infarction, on autopsy, despite having patent coronary arteries<ref name="pmid17606843">{{cite journal| author=Becattini C, Vedovati MC, Agnelli G| title=Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. | journal=Circulation | year= 2007 | volume= 116 | issue= 4 | pages= 427-33 | pmid=17606843 | doi=10.1161/CIRCULATIONAHA.106.680421 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17606843  }} </ref> <ref name="pmid19465511">{{cite journal| author=Jiménez D, Uresandi F, Otero R, Lobo JL, Monreal M, Martí D et al.| title=Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. | journal=Chest | year= 2009 | volume= 136 | issue= 4 | pages= 974-82 | pmid=19465511 | doi=10.1378/chest.09-0608 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19465511  }} </ref>.


*'''Additional Risk Markers'''
* The average annual rates of hospitalizations with a discharge diagnosis of [[DVT]], [[PE]], or [[VTE]] among adults were 152, 121, and 239 per 100,000 population, respectively. For [[VTE]], the average annual rates were 60 per 100,000 population aged 18–39 years, 143 for persons aged 40–49 years, 200 for persons aged 50–59 years, 391 for persons aged 60–69 years, 727 for persons aged 70–79 years, and 1,134 for persons aged ≥80 years. The rates of [[hospitalization]] were similar for men and women, and the point estimates increased for both sexes by age.<ref name=CDC2> [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6122a1.htm?s_cid=mm6122a1_w ] Hussain R. Yusuf, MD, James Tsai, MD, Hani K. Atrash, MD, Sheree Boulet, DrPH, Scott D. Grosse, PhD, Div of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, CDC. Venous Thromboembolism in Adult Hospitalizations — United States, 2007–2009</ref>
**[[Deep vein thrombosis|DVT]]
**[[Hyponatremia]]
Hyponatremia at the time of presentation is associated with
*Increased mortality
*Hospital readmission.


There is controversy over, treatment of small subsegmental PE<ref>{{cite journal |author=Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F |title=Diagnosis and management of subsegmental pulmonary embolism |journal=J Thromb Haemost |volume=4 |issue=4 |pages=724-31 |year=2006 |pmid=16634736}}</ref> and some evidence exists that patients with subsegmental PEs may do well without treatment.<ref name="pmid16738276">{{cite journal |author=Perrier A, Bounameaux H |title=Accuracy or outcome in suspected pulmonary embolism |journal=N Engl J Med |volume=354 |issue=22 |pages=2383-5 |year=2006 |pmid=16738276|url=http://content.nejm.org/cgi/content/full/354/22/2383}}</ref><ref name="pmid16738268">{{cite journal |author=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 |title=Multidetector computed tomography for acute pulmonary embolism |journal=N Engl J Med |volume=354 |issue=22 |pages=2317-27 |year=2006 |pmid=16738268}}</ref>
* On average, 28,726 hospitalized adults with a [[VTE]] diagnosis died each year. Of these patients, an average of 13,164 had a [[DVT]] diagnosis and 19,297 had a PE diagnosis; 3,735 had both [[DVT]] and [[PE]] diagnoses.<ref name=CDC2> [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6122a1.htm?s_cid=mm6122a1_w ] Hussain R. Yusuf, MD, James Tsai, MD, Hani K. Atrash, MD, Sheree Boulet, DrPH, Scott D. Grosse, PhD, Div of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, CDC. Venous Thromboembolism in Adult Hospitalizations — United States, 2007–2009</ref>


ECG findings can also help in assessing the prognosis. Please click [[Pulmonary embolism electrocardiogram#Prognostic Assessment|'''here''']] to read more.
===Recurrence of VTE===
* There are mixed results regarding the rate of [[PE]] recurrence which ranged in the literature from as low as 2 to 50%.<ref name="pmid4710405">{{cite journal| author=Paraskos JA, Adelstein SJ, Smith RE, Rickman FD, Grossman W, Dexter L et al.| title=Late prognosis of acute pulmonary embolism. | journal=N Engl J Med | year= 1973 | volume= 289 | issue= 2 | pages= 55-8 | pmid=4710405 | doi=10.1056/NEJM197307122890201 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4710405  }} </ref><ref name="pmid13735229">{{cite journal| author=PHEAR D| title=Pulmonary embolism. A study of late prognosis. | journal=Lancet | year= 1960 | volume= 2 | issue= 7155 | pages= 832-5 | pmid=13735229 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13735229  }} </ref><ref name="pmid1560799">{{cite journal| author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI et al.| title=The clinical course of pulmonary embolism. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 19 | pages= 1240-5 | pmid=1560799 | doi=10.1056/NEJM199205073261902 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1560799  }} </ref>  According to some reports, one-third (about 33%) of people with VTE will have a recurrence within 10 years.<ref>[http://www.cdc.gov/ncbddd/dvt/data.html CDC- Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) — Blood Clot Forming in a Vein]</ref><ref name="pmid20331949">{{cite journal| author=Beckman MG, Hooper WC, Critchley SE, Ortel TL| title=Venous thromboembolism: a public health concern. | journal=Am J Prev Med | year= 2010 | volume= 38 | issue= 4 Suppl | pages= S495-501 | pmid=20331949 | doi=10.1016/j.amepre.2009.12.017 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20331949  }} </ref>  A follow up period of 2.2 years of subsequent observation of 265 patients reported that the risk of recurrence of [[VTE]] in patients diagnosed with first-time [[VTE]] to be around 7-8 percent per year. <ref name="pmid15210384">{{cite journal |author=Cushman M, Tsai AW, White RH, ''et al.''|title=Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology |journal=Am. J. Med.|volume=117 |issue=1 |pages=19–25 |year=2004 |month=July |pmid=15210384 |doi=10.1016/j.amjmed.2004.01.018 |url=}}</ref>


==Complications==
* Among patients with a first episode of [[VTE]], the risk of recurrence of [[VTE]] is elevated in the first 6 to 12 months following the first episode of [[VTE]], particularly in the first week.  The risk of recurrent [[VTE]] remains up to 10 years, with an estimated cumulative incidence of first overall [[VTE]] recurrence of 30 %.  Predictors for recurrence of [[VTE]] include [[malignancy]], [[neurological]] diseases, and [[paresis]].<ref name="pmid10737275">{{cite journal |author=Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ |title=Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study |journal=Arch. Intern. Med. |volume=160 |issue=6 |pages=761–8 |year=2000 |month=March |pmid=10737275 |doi= |url=}}</ref>
*[[Heart failure]] or [[shock]]
 
*[[Palpitations]]
===Mortality===
*[[Pulmonary hypertension]]
* The hospital [[mortality rates]] of [[PE]] in untreated PE patients and treated PE patients are approximately 30% and 8%, respectively.<ref name="pmid13713631">{{cite journal| author=HERMANN RE, DAVIS JH, HOLDEN WD| title=Pulmonary embolism. A clinical and pathologic study with emphasis on the effect of prophylactic therapy with anticoagulants. | journal=Am J Surg | year= 1961 | volume= 102 | issue=  | pages= 19-28 | pmid=13713631 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13713631  }} </ref><ref name="pmid14063921">{{cite journal| author=MORRELL MT, TRUELOVE SC, BARR A| title=PULMONARY EMBOLISM. | journal=Br Med J | year= 1963 | volume= 2 | issue= 5361 | pages= 830-5 | pmid=14063921 | doi= | pmc=PMC1872984 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14063921  }} </ref><ref name="pmid13797091">{{cite journal| author=BARRITT DW, JORDAN SC| title=Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. | journal=Lancet | year= 1960 | volume= 1 | issue= 7138 | pages= 1309-12 | pmid=13797091 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13797091  }} </ref> Unfortunately, two-thirds of all PE cases are diagnosed by autopsy. <ref name="AHA2007"> 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 </ref> Pulmonary embolism causes death in approximately 16% of hospitalized patients.
*Severe [[dyspnea]]
 
*Severe bleeding (usually a complication of treatment)
* A 26% [[mortality rate]] associated with untreated [[PE]] is often cited based upon a trial published in 1960 by Barrit and Jordan<ref name="Barritt">{{cite journal | Barritt DW, Jorden SC | title=Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. | journal=[[The Lancet|Lancet]] | year=1960 | volume=1 | pages=1309&ndash;1312 | id=PMID 13797091 }}</ref> 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 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 underestimate the true mortality insofar as the sensitivity and specificity of diagnostic technology in 1957 may have only allowed the detection of massive PE.
*Sudden death
 
* Factors that are associated with an elevated rate of mortality in PE are:<ref name="pmid1560799">{{cite journal| author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI et al.| title=The clinical course of pulmonary embolism. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 19 | pages= 1240-5 | pmid=1560799 | doi=10.1056/NEJM199205073261902 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1560799  }} </ref>
** Age >60 years
** [[Congestive heart failure]]
** [[Pulmonary hypertension]]
** [[Ischemic heart disease]]
** [[Chronic]] [[lung]] disease
** [[Cancer]]
** [[Stroke]]
 
* The presence of [[congestive heart failure]] or [[cancer]] are independent correlates of increased mortality in PE.<ref name="pmid1560799">{{cite journal| author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI et al.| title=The clinical course of pulmonary embolism. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 19 | pages= 1240-5 | pmid=1560799 | doi=10.1056/NEJM199205073261902 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1560799  }} </ref>
 
* The one year mortality in patients who had an episode of PE was reported to be approximately 24%, only 2.5% of which is due to PE itself (usually within the first two weeks) while the two third of one-year mortality is due to other medical conditions such as [[heart]] disease, [[lung]] disease, [[cancer]], or [[sepsis]].<ref name="pmid1560799">{{cite journal| author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI et al.| title=The clinical course of pulmonary embolism. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 19 | pages= 1240-5 | pmid=1560799 | doi=10.1056/NEJM199205073261902 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1560799  }} </ref>
 
* The rate of PE-related mortality varies according to the severity of PE:
**Massive PE, also known as high risk PE, is associated with a rate PE-related early mortality of > 15%.<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=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). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref>
**Submassive PE, also known as intermediate risk PE, is associated with a rate of PE-related early mortality ranging from 3 to 15%.<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=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). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref>
** Low risk PE is associated with a rate of PE-related early mortality of <1%.<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=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). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref>
 
* Estimates suggest that 60,000-100,000 Americans die of [[VTE]], 10 to 30% of which will die within one month of diagnosis.<ref>[http://www.cdc.gov/ncbddd/dvt/data.html CDC- [[Deep Vein Thrombosis]] (DVT) / [[Pulmonary Embolism]] (PE) — Blood Clot Forming in a Vein]</ref><ref name="pmid20331949">{{cite journal| author=Beckman MG, Hooper WC, Critchley SE, Ortel TL| title=Venous thromboembolism: a public health concern. | journal=Am J Prev Med | year= 2010 | volume= 38 | issue= 4 Suppl | pages= S495-501 | pmid=20331949 | doi=10.1016/j.amepre.2009.12.017 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20331949  }} </ref>
 
* An analysis of multiple-cause mortality files compiled by the National Center for Health Statistics from 1979 to 1998 reported that out of 42,932,973 deaths that occurred, almost 600,000 patients (approximately 1.5 percent) had been diagnosed with PE. PE might have caused the death of 200,000 of those patients.<ref name="pmid12885687">{{cite journal| author=Horlander KT, Mannino DM, Leeper KV| title=Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. | journal=Arch Intern Med | year= 2003 |volume= 163 | issue= 14 | pages= 1711-7 | pmid=12885687 | doi=10.1001/archinte.163.14.1711 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12885687  }}</ref>
 
===Clinical Correlates of Mortality among Patients with PE===
==== 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.<ref name="pmid9350909">{{cite journal| author=Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD et al.| title=Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. | journal=J Am Coll Cardiol | year= 1997 | volume= 30 | issue= 5 | pages= 1165-71 | pmid=9350909 | doi= | pmc=| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9350909 }} </ref>  The MAPPET study demonstrated that [[systemic]] [[shock]] was associated with mortality of 24.5% whereas [[hypotension]] (but not [[shock]]) was associated with a 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]].<ref name="pmid16432055">{{cite journal| author=Kucher N, Rossi E, De Rosa M, Goldhaber SZ| title=Massive pulmonary embolism. | journal=Circulation | year= 2006 | volume= 113 | issue= 4 | pages= 577-82 |pmid=16432055 | doi=10.1161/CIRCULATIONAHA.105.592592 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16432055  }} </ref>
 
==== Markers of Right Ventricular Dysfunction (RVD)  ====
The presence of [[right ventricular dysfunction|right ventricular dysfunction (RVD)]] on [[echocardiography]] has been associated with a higher mortality in the setting of pulmonary embolism.<ref name="pmid16234620">{{cite journal| author=Konstantinides S| title=Pulmonary embolism: impact of right ventricular dysfunction. | journal=Curr Opin Cardiol | year= 2005 | volume= 20 | issue= 6 | pages= 496-501 | pmid=16234620 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16234620  }} </ref><ref name="pmid8094768">{{cite journal| author=Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL et al.| title=Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. | journal=Lancet | year= 1993 | volume= 341 | issue= 8844 | pages= 507-11 | pmid=8094768 | doi= | pmc= | url= }} </ref><ref name="pmid9327706">{{cite journal| author=Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L| title=Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. | journal=Am Heart J | year= 1997 | volume= 134 | issue= 3 | pages= 479-87 | pmid=9327706 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9327706  }} </ref><ref name="pmid9155614">{{cite journal| author=Kasper W, Konstantinides S, Geibel A, Tiede N, Krause T, Just H| title=Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism. | journal=Heart | year= 1997 | volume= 77 | issue= 4 | pages= 346-9 | pmid=9155614 | doi= | pmc=PMC484729 | url= }} </ref><ref name="pmid10859287">{{cite journal| author=Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G et al.| title=Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. | journal=Circulation | year= 2000 | volume= 101 | issue= 24 | pages= 2817-22 | pmid=10859287 | doi= | pmc= | url= }} </ref><ref name="pmid16087827">{{cite journal| author=Kucher N, Rossi E, De Rosa M, Goldhaber SZ| title=Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher. | journal=Arch Intern Med | year= 2005 | volume= 165 | issue= 15 | pages= 1777-81 | pmid=16087827 | doi=10.1001/archinte.165.15.1777 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16087827  }} </ref>
 
==== 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.<ref name="pmid18626627">{{cite journal| author=Cavallazzi R, Nair A, Vasu T, Marik PE| title=Natriuretic peptides in acute pulmonary embolism: a systematic review. | journal=Intensive Care Med | year= 2008 | volume= 34 | issue= 12 | pages= 2147-56 | pmid=18626627 | doi=10.1007/s00134-008-1214-5 | pmc= | url= }} </ref> 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.<ref name="pmid19214022">{{cite journal| author=Alonso-Martínez JL, Urbieta-Echezarreta M, Anniccherico-Sánchez FJ, Abínzano-Guillén ML, Garcia-Sanchotena JL| title=N-terminal pro-B-type natriuretic peptide predicts the burden of pulmonary embolism. | journal=Am J Med Sci | year= 2009 | volume= 337 | issue= 2 | pages= 88-92 | pmid=19214022 |doi=10.1097/MAJ.0b013e318182d33e | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19214022  }} </ref>
 
==== 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 epicardial [[coronary artery disease]] but rather transmural [[RV]] [[infarctions]] on [[autopsy]].<ref name="pmid17606843">{{cite journal| author=Becattini C, Vedovati MC, Agnelli G| title=Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. | journal=Circulation | year= 2007 | volume= 116 | issue= 4 | pages= 427-33 | pmid=17606843 | doi=10.1161/CIRCULATIONAHA.106.680421 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17606843  }} </ref> <ref name="pmid19465511">{{cite journal| author=Jiménez D, Uresandi F, Otero R, Lobo JL, Monreal M, Martí D et al.| title=Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. | journal=Chest | year= 2009 | volume= 136 | issue= 4 | pages= 974-82 | pmid=19465511 | doi=10.1378/chest.09-0608 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19465511  }} </ref>
 
==== Hyponatremia ====
[[Hyponatremia]] at the time of presentation of PE is associated with increased mortality and hospital readmission.<ref name="pmid20595225">{{cite journal| author=Scherz N, Labarère J, Méan M, Ibrahim SA, Fine MJ, Aujesky D| title=Prognostic importance of hyponatremia in patients with acute pulmonary embolism. | journal=Am J Respir Crit Care Med | year= 2010 | volume= 182 | issue= 9 | pages= 1178-83 | pmid=20595225 | doi=10.1164/rccm.201003-0481OC | pmc=PMC3001260 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20595225  }} </ref>


==== Electrocardiographic Abnormalities ====
The [[electrocardiographic]] findings in pulmonary embolism lack [[specificity]] and [[sensitivity]] and their prognostic value is limited.  Development of a [[QR wave]] in lead V<sub>1</sub> has been identified as an independent risk factor for an adverse [[prognosis]].<ref name="pmid12804925">{{cite journal |author=Kucher N, Walpoth N, Wustmann K, Noveanu M, Gertsch M |title=QR in V1--an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism |journal=[[European Heart Journal]] |volume=24 |issue=12 |pages=1113–9 |year=2003 |month=June |pmid=12804925 |doi= |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12804925 |accessdate=2011-12-05}}</ref>


==ESC Guidelines for Prognostic assessment (DO NOT EDIT)==
==ESC 2008 Guidelines for Prognostic Assessment (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>==
<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>
{{cquote|
===[[European society of cardiology#Classes of Recommendations|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. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''


===[[European society of cardiology#Classes of Recommendations|Class II]]===
{|class="wikitable"
'''2.'''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 [[RV dysfunction|RVD]] and myocardial injury should be considered.''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])''}}
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''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. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


==Guidelines Resources==
{|class="wikitable"
*Guidelines on the diagnosis and management of acute pulmonary embolism<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>.
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[European society of cardiology#Classes of Recommendations|Class II]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''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 [[RV dysfunction|RVD]] and myocardial injury should be considered.''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


==References==
==References==
{{reflist|2}}
{{reflist|2}}
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Latest revision as of 23:53, 29 July 2020



Resident
Survival
Guide

Pulmonary Embolism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Pulmonary Embolism from other Diseases

Epidemiology and Demographics

Risk Factors

Triggers

Natural History, Complications and Prognosis

Diagnosis

Diagnostic criteria

Assessment of Clinical Probability and Risk Scores

Pulmonary Embolism Assessment of Probability of Subsequent VTE and Risk Scores

History and Symptoms

Physical Examination

Laboratory Findings

Arterial Blood Gas Analysis

D-dimer

Biomarkers

Electrocardiogram

Chest X Ray

Ventilation/Perfusion Scan

Echocardiography

Compression Ultrasonography

CT

MRI

Treatment

Treatment approach

Medical Therapy

IVC Filter

Pulmonary Embolectomy

Pulmonary Thromboendarterectomy

Discharge Care and Long Term Treatment

Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Follow-Up

Support group

Special Scenario

Pregnancy

Cancer

Trials

Landmark Trials

Case Studies

Case #1

Pulmonary embolism natural history, complications and prognosis On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Pulmonary embolism natural history, complications and prognosis

CDC on Pulmonary embolism natural history, complications and prognosis

Pulmonary embolism natural history, complications and prognosis in the news

Blogs on Pulmonary embolism natural history, complications and prognosis

Directions to Hospitals Treating Pulmonary embolism natural history, complications and prognosis

Risk calculators and risk factors for Pulmonary embolism natural history, complications and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] The APEX Trial Investigators; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [3]

Overview

Pulmonary embolism (PE) 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 PE 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 PE die, typically from recurrent PE. However, with prompt diagnosis and treatment, the mortality rate is approximately 2–8%. The true mortality associated with PE may be underestimated as two-thirds of all PE cases are diagnosed by autopsy. Estimates suggest that 60,000-100,000 Americans die of VTE, 10 to 30% of which will die within one month of diagnosis. Sudden death is the first symptom in about one-quarter (25%) of people who have a PE. One-third (about 33%) of people with VTE will have a recurrence within 10 years.[1][2]

Subsegmental pulmonary emboli may[3] or may not[4] have a favorable prognosis.

Complications

Acute Complications

Chronic Complications

Complications of Firbrinolytic Therapy for Pulmonary Embolism[6]

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

Prognosis

Pulmonary Embolism Severity Index (PESI) Score

The Pulmonary Embolism Severity Index (PESI) score aims to stratify patients with PE into classes of increasing rate of mortality and adverse outcomes.[7]

Calculation of PESI Score

Age, per yr Age, in yr
Male sex 10
Cancer 30
Heart failure 10
Chronic lung disease 10
Pulse ≥110 beat/min 20
Systolic blood pressure <100 mmHg 30
Respiratory rate ≥30/min 20
Temperature <36 20
Altered mental status 60
Arterial oxygen saturation <90% 20

Interpretation of PESI Score

Class Score Class–specific 30-day mortality
Class I, very low risk ≤65 1.1%
Class II, low risk 65-85 3.1%
Class III, intermediate risk 86-105 6.5%
Class IV, high risk 106-125 10.4%
Class V, very high risk >125 24.5%

HOPPE risk score

The HOPPE risk score contains[8]:

The HOPPE has not been studied as extensively as PESI; however, initial study suggests it may prove more accurate.[8]

Hestia Clinical Decision Rule

The Hestia Clinical Decision Rule can help guide the decision for hospitalization.[9]

Hospitalization for VTE

  • During 2007–2009, an estimated annual average of 547,596 hospitalizations had a diagnosis of VTE for adults aged ≥18 years. Estimates for DVT and PE diagnoses were not mutually exclusive. An estimated annual average of 348,558 adult hospitalizations had a diagnosis of DVT, and 277,549 adult hospitalizations had a diagnosis of PE. An estimated annual average of 78,511 adult hospitalizations (14% of overall VTE hospitalizations) had diagnoses of both DVT and PE.[10]
  • The estimated average annual number of hospitalizations with VTE was successively greater among older age groups: 54,034 for persons aged 18–39 years; 143,354 for persons aged 40–59 years; and 350,208 for persons aged ≥60 years. The estimated average annual number of hospitalizations with VTE was comparable for men (250,973) and women (296,623).[10] Shown below is an image depicting the estimated average annual number of hospitalization with a diagnosis of DVT, PE, or VTE by age and sex (image courtesy of CDC.gov[10]).

  • The average annual rates of hospitalizations with a discharge diagnosis of DVT, PE, or VTE among adults were 152, 121, and 239 per 100,000 population, respectively. For VTE, the average annual rates were 60 per 100,000 population aged 18–39 years, 143 for persons aged 40–49 years, 200 for persons aged 50–59 years, 391 for persons aged 60–69 years, 727 for persons aged 70–79 years, and 1,134 for persons aged ≥80 years. The rates of hospitalization were similar for men and women, and the point estimates increased for both sexes by age.[10]
  • On average, 28,726 hospitalized adults with a VTE diagnosis died each year. Of these patients, an average of 13,164 had a DVT diagnosis and 19,297 had a PE diagnosis; 3,735 had both DVT and PE diagnoses.[10]

Recurrence of VTE

  • There are mixed results regarding the rate of PE recurrence which ranged in the literature from as low as 2 to 50%.[11][12][13] According to some reports, one-third (about 33%) of people with VTE will have a recurrence within 10 years.[14][2] A follow up period of 2.2 years of subsequent observation of 265 patients reported that the risk of recurrence of VTE in patients diagnosed with first-time VTE to be around 7-8 percent per year. [15]
  • Among patients with a first episode of VTE, the risk of recurrence of VTE is elevated in the first 6 to 12 months following the first episode of VTE, particularly in the first week. The risk of recurrent VTE remains up to 10 years, with an estimated cumulative incidence of first overall VTE recurrence of 30 %. Predictors for recurrence of VTE include malignancy, neurological diseases, and paresis.[16]

Mortality

  • The hospital mortality rates of PE in untreated PE patients and treated PE patients are approximately 30% and 8%, respectively.[17][18][19] Unfortunately, two-thirds of all PE cases are diagnosed by autopsy. [20] Pulmonary embolism causes death in approximately 16% of hospitalized patients.
  • A 26% mortality rate associated with untreated PE is often cited based upon a trial published in 1960 by Barrit and Jordan[21] 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 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 underestimate the true mortality insofar as the sensitivity and specificity of diagnostic technology in 1957 may have only allowed the detection of massive PE.
  • The one year mortality in patients who had an episode of PE was reported to be approximately 24%, only 2.5% of which is due to PE itself (usually within the first two weeks) while the two third of one-year mortality is due to other medical conditions such as heart disease, lung disease, cancer, or sepsis.[13]
  • The rate of PE-related mortality varies according to the severity of PE:
    • Massive PE, also known as high risk PE, is associated with a rate PE-related early mortality of > 15%.[22]
    • Submassive PE, also known as intermediate risk PE, is associated with a rate of PE-related early mortality ranging from 3 to 15%.[22]
    • Low risk PE is associated with a rate of PE-related early mortality of <1%.[22]
  • Estimates suggest that 60,000-100,000 Americans die of VTE, 10 to 30% of which will die within one month of diagnosis.[23][2]
  • An analysis of multiple-cause mortality files compiled by the National Center for Health Statistics from 1979 to 1998 reported that out of 42,932,973 deaths that occurred, almost 600,000 patients (approximately 1.5 percent) had been diagnosed with PE. PE might have caused the death of 200,000 of those patients.[24]

Clinical Correlates of Mortality among Patients with PE

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.[25] The MAPPET study demonstrated that systemic shock was associated with mortality of 24.5% whereas hypotension (but not shock) was associated with a 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.[26]

Markers of Right Ventricular Dysfunction (RVD)

The presence of right ventricular dysfunction (RVD) on echocardiography has been associated with a higher mortality in the setting of pulmonary embolism.[27][28][29][30][31][32]

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.[33] 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.[34]

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 epicardial coronary artery disease but rather transmural RV infarctions on autopsy.[35] [36]

Hyponatremia

Hyponatremia at the time of presentation of PE is associated with increased mortality and hospital readmission.[37]

Electrocardiographic Abnormalities

The electrocardiographic findings in pulmonary embolism lack specificity and sensitivity and their prognostic value is limited. Development of a QR wave in lead V1 has been identified as an independent risk factor for an adverse prognosis.[38]

ESC 2008 Guidelines for Prognostic Assessment (DO NOT EDIT)[22]

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. CDC- Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) — Blood Clot Forming in a Vein
  2. 2.0 2.1 2.2 Beckman MG, Hooper WC, Critchley SE, Ortel TL (2010). "Venous thromboembolism: a public health concern". Am J Prev Med. 38 (4 Suppl): S495–501. doi:10.1016/j.amepre.2009.12.017. PMID 20331949.
  3. Carrier M, Righini M, Wells PS, Perrier A, Anderson DR, Rodger MA; et al. (2010). "Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies". J Thromb Haemost. 8 (8): 1716–22. doi:10.1111/j.1538-7836.2010.03938.x. PMID 20546118.
  4. den Exter PL, van Es J, Klok FA, Kroft LJ, Kruip MJ, Kamphuisen PW; et al. (2013). "Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism". Blood. 122 (7): 1144–9, quiz 1329. doi:10.1182/blood-2013-04-497545. PMID 23736701.
  5. "Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) : The Lancet". Retrieved 2012-10-07.
  6. "Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism". Retrieved 2012-10-06.
  7. Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J; et al. (2005). "Derivation and validation of a prognostic model for pulmonary embolism". Am J Respir Crit Care Med. 172 (8): 1041–6. doi:10.1164/rccm.200506-862OC. PMC 2718410. PMID 16020800.
  8. 8.0 8.1 Subramanian M, Gopalan S, Ramadurai S, Arthur P, Prabhu MA, Thachathodiyl R; et al. (2017). "Derivation and Validation of a Novel Prediction Model to Identify Low-Risk Patients With Acute Pulmonary Embolism". Am J Cardiol. 120 (4): 676–681. doi:10.1016/j.amjcard.2017.05.043. PMID 28683900.
  9. den Exter PL, Zondag W, Klok FA, Brouwer RE, Dolsma J, Eijsvogel M; et al. (2016). "Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial". Am J Respir Crit Care Med. 194 (8): 998–1006. doi:10.1164/rccm.201512-2494OC. PMID 27030891.
  10. 10.0 10.1 10.2 10.3 10.4 [1] Hussain R. Yusuf, MD, James Tsai, MD, Hani K. Atrash, MD, Sheree Boulet, DrPH, Scott D. Grosse, PhD, Div of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, CDC. Venous Thromboembolism in Adult Hospitalizations — United States, 2007–2009
  11. Paraskos JA, Adelstein SJ, Smith RE, Rickman FD, Grossman W, Dexter L; et al. (1973). "Late prognosis of acute pulmonary embolism". N Engl J Med. 289 (2): 55–8. doi:10.1056/NEJM197307122890201. PMID 4710405.
  12. PHEAR D (1960). "Pulmonary embolism. A study of late prognosis". Lancet. 2 (7155): 832–5. PMID 13735229.
  13. 13.0 13.1 13.2 13.3 Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI; et al. (1992). "The clinical course of pulmonary embolism". N Engl J Med. 326 (19): 1240–5. doi:10.1056/NEJM199205073261902. PMID 1560799.
  14. CDC- Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) — Blood Clot Forming in a Vein
  15. Cushman M, Tsai AW, White RH; et al. (2004). "Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology". Am. J. Med. 117 (1): 19–25. doi:10.1016/j.amjmed.2004.01.018. PMID 15210384. Unknown parameter |month= ignored (help)
  16. Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ (2000). "Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study". Arch. Intern. Med. 160 (6): 761–8. PMID 10737275. Unknown parameter |month= ignored (help)
  17. HERMANN RE, DAVIS JH, HOLDEN WD (1961). "Pulmonary embolism. A clinical and pathologic study with emphasis on the effect of prophylactic therapy with anticoagulants". Am J Surg. 102: 19–28. PMID 13713631.
  18. MORRELL MT, TRUELOVE SC, BARR A (1963). "PULMONARY EMBOLISM". Br Med J. 2 (5361): 830–5. PMC 1872984. PMID 14063921.
  19. BARRITT DW, JORDAN SC (1960). "Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial". Lancet. 1 (7138): 1309–12. PMID 13797091.
  20. 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
  21. "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)
  22. 22.0 22.1 22.2 22.3 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.
  23. CDC- Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) — Blood Clot Forming in a Vein
  24. Horlander KT, Mannino DM, Leeper KV (2003). "Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data". Arch Intern Med. 163 (14): 1711–7. doi:10.1001/archinte.163.14.1711. PMID 12885687.
  25. 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.
  26. 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.
  27. Konstantinides S (2005). "Pulmonary embolism: impact of right ventricular dysfunction". Curr Opin Cardiol. 20 (6): 496–501. PMID 16234620.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. Scherz N, Labarère J, Méan M, Ibrahim SA, Fine MJ, Aujesky D (2010). "Prognostic importance of hyponatremia in patients with acute pulmonary embolism". Am J Respir Crit Care Med. 182 (9): 1178–83. doi:10.1164/rccm.201003-0481OC. PMC 3001260. PMID 20595225.
  38. Kucher N, Walpoth N, Wustmann K, Noveanu M, Gertsch M (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 2011-12-05. Unknown parameter |month= ignored (help)

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