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. [2]; 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]

Complications

Acute Complications

Chronic Complications

Complications of Firbrinolytic Therapy for Pulmonary Embolism[4]

  • 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.[5]

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%

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.[6]
  • 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).[6] 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[6]).

Estimated average annual number of hospitalization VTE.gif

  • 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.[6]
  • 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.[6]

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%.[7][8][9] According to some reports, one-third (about 33%) of people with VTE will have a recurrence within 10 years.[10][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. [11]
  • 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 a estimated cumulative incidence of first overall VTE recurrence of 30 %. Predictors for recurrence of VTE include malignancy, neurological diseases, and paresis.[12]

Mortality

  • The hospital mortality rates of PE in untreated PE patients and treated PE patients are approximately 30% and 8%, respectively.[13][14][15] Unfortunately, two-thirds of all PE cases are diagnosed by autopsy. [16] 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[17] 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.[9]
  • 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%.[18]
    • Submassive PE, also known as intermediate risk PE, is associated with a rate of PE-related early mortality ranging from 3 to 15%.[18]
    • Low risk PE is associated with a rate of PE-related early mortality of <1%.[18]
  • Estimates suggest that 60,000-100,000 Americans die of VTE, 10 to 30% of which will die within one month of diagnosis.[19][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.[20]

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.[21] 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.[22]

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.[23][24][25][26][27][28]

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.[29] 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.[30]

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.[31] [32]

Hyponatremia

Hyponatremia at the time of presentation of PE is associated with increased mortality and hospital readmission.[33]

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.[34]

ESC 2008 Guidelines for Prognostic Assessment (DO NOT EDIT)[18]

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

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  3. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) : The Lancet. Retrieved on 2012-10-07.
  4. Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism. Retrieved on 2012-10-06.
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