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Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism

Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism
Authors:
B Taylor Thompson, MD
Christopher Kabrhel, MD, MPH
Constantino Pena, MD
Section Editors:
Jess Mandel, MD, MACP, ATSF, FRCP
Korilyn S Zachrison, MD, MSc
Deputy Editor:
Geraldine Finlay, MD
Literature review current through: Jul 2022. | This topic last updated: Mar 30, 2022.

INTRODUCTION — Acute pulmonary embolism (PE) is a common and sometimes fatal disease. The approach to the evaluation should be efficient while simultaneously avoiding the risks of unnecessary testing so that therapy can be promptly initiated and potential morbidity and mortality avoided [1].

The clinical manifestations, evaluation, and diagnosis of PE are discussed in this topic. The pathophysiology, treatment, and prognosis of PE as well as the diagnosis of PE during pregnancy are reviewed separately. (See "Overview of acute pulmonary embolism in adults" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults" and "Diagnosis of pulmonary embolism in pregnancy".) (Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically stable and Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically unstable despite resuscitative efforts.)

Approaches to diagnosis outlined in this topic are, in general, consistent with strategies outlined by several international societies including The American College of Physicians, The European Society of Cardiology, The European Respiratory Society, American College of Emergency Physicians, and others [1-4].  

CLINICAL PRESENTATION — PE has a wide variety of presenting features, ranging from no symptoms to shock or sudden death [5-8]. The most common presenting symptom is dyspnea followed by chest pain (classically pleuritic but often dull) and cough. However, many patients, including those with large PE, have mild or nonspecific symptoms or are asymptomatic. For example, a meta-analysis of 19 studies (25,343 patients) found that clinical impression alone had a sensitivity and specificity of 85 and 51 percent, respectively, for the diagnosis of PE [9].Thus, it is critical that a high level of suspicion be maintained such that clinically relevant cases are not missed.

History and examination — The most common symptoms in patients with PE were identified in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) group (table 1) [6]. They include the following:

Dyspnea at rest or with exertion (73 percent)

Pleuritic pain (66 percent)

Cough (37 percent)

Orthopnea (28 percent)

Calf or thigh pain and/or swelling (44 percent)

Wheezing (21 percent)

Hemoptysis (13 percent)

Less common presentations include transient or persistent arrhythmias (eg, atrial fibrillation), presyncope, syncope, and hemodynamic collapse (<10 percent each) [10,11]. Hoarseness from a dilated pulmonary artery is a rare presentation (Ortner syndrome) [12].

The onset of dyspnea is frequently (but not always) rapid, usually within seconds (46 percent) or minutes (26 percent) [8]. Dyspnea may be less frequent in older patients with no previous cardiopulmonary disease. Dyspnea is more likely to be present in patients who present with PE in the main or lobar vessels.

Approximately 10 percent of patients present with the symptoms of an infarcted lung, usually due to smaller, more peripheral emboli. Pleuritic pain is typical in this population due to inflammation of the pleura. Hemorrhage from the infarcted lung is also thought to be responsible for hemoptysis. (See "Overview of acute pulmonary embolism in adults", section on 'Pathogenesis and pathophysiology'.)

Retrospective studies report syncope as the presenting symptom in 10 percent or less of cases. Conversely, among those presenting with syncope, rates of PE ranging from 1 to 17 percent have been reported [13-21]. Rates may be higher in those hospitalized with syncope [18,21]. Highlighting syncope as a manifestation of PE, 560 patients seen in an emergency department (ED) with a first episode of syncope who were admitted to hospital underwent a rigorous investigation for PE that involved D-dimer and computed tomography pulmonary arteriography (CTPA) [18]. In this population, the prevalence of PE was 17 percent, higher in those who had no other identifiable etiology for syncope (25 percent). Although those discharged from the ED did not undergo formal evaluation for PE, when they were included in the analysis, the rate of PE was lower and closer to that seen in other retrospective studies (4 percent). Syncope may indicate a high burden of thrombus since up to two-thirds of patients with PE who present with syncope have large thrombi located in the mainstem or lobar arteries [10,11]. The reasons for syncope in patients with PE are poorly understood but may be partially explained by transient arrhythmias as thrombus travels through the heart or transient obstruction as the embolus transits the pulmonic valve.

Some patients have a delayed presentation over weeks or days. One prospective study reported that patients with a delayed presentation beyond one week tended to have larger, more centrally located PE compared with patients who presented within seven days (41 versus 26 percent) [22]. Symptoms and signs of PE may also evolve over time such that patients who initially present with mild symptoms may become increasingly symptomatic or hemodynamically unstable, sometimes very quickly (minutes to hours). This may be secondary to recurrent embolization or progressive pulmonary hypertension secondary to vasoconstriction. Similarly, as a pulmonary infarct evolves, patients may develop progressive dyspnea, hypoxemia, pleuritic pain, and hemoptysis. (See "Overview of acute pulmonary embolism in adults", section on 'Pathogenesis and pathophysiology'.)

Importantly, symptoms may be mild or absent, even in large PE [5,8,23]. Although the true incidence of asymptomatic PE is unknown, one systematic review of 28 studies found that, among the 5233 patients who had a deep vein thrombosis (DVT), one-third also had asymptomatic PE [23].

Common presenting signs on examination include [8]:

Tachypnea (54 percent)

Calf or thigh swelling, erythema, edema, tenderness, palpable cords (47 percent)

Tachycardia (24 percent)

Rales (18 percent)

Decreased breath sounds (17 percent)

An accentuated pulmonic component of the second heart sound (15 percent)

Jugular venous distension (14 percent)

Fever, mimicking pneumonia (3 percent)

Although upper extremity DVT (UEDVT) embolizes less commonly than lower extremity DVT, symptoms of UEDVT (eg, arm pain or tightness) should also raise the suspicion of PE. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity" and "Overview of thoracic central venous obstruction".)

PE is a common cause of sudden cardiac arrest or circulatory collapse (8 percent), especially among patients younger than 65 years old [8,24,25]. Among such patients, either dyspnea or tachypnea is present in 91 percent. Massive PE may be accompanied by acute right ventricular failure manifested by increased jugular venous pressure, a right-sided third heart sound, a parasternal lift, cyanosis, and obstructive shock. However, shock may also develop in patients with smaller PE who have severe underlying pulmonary hypertension. A transition from tachycardia to bradycardia, or from a narrow complex to a broad complex tachycardia (ie, right bundle branch block), is an ominous sign of right ventricular strain and impending shock. PE should be suspected anytime there is hypotension accompanied by an elevated central venous pressure that is not otherwise explained by acute myocardial infarction, tension pneumothorax, pericardial tamponade, or a new arrhythmia [26,27]. (See "Definition, classification, etiology, and pathophysiology of shock in adults".)

Laboratory tests — Laboratory tests are not diagnostic but alter the clinical suspicion for PE, confirm the presence of alternative diagnoses, and provide prognostic information in the event that PE is diagnosed:

Complete blood count and serum chemistries – Routine laboratory findings include leukocytosis, increased erythrocyte sedimentation rate (ESR), elevated serum lactate, elevated serum lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Serum creatinine and the estimated glomerular filtration rate (eGFR) helps determine the safety of administering contrast for angiography.

Arterial blood gas (ABG) and pulse oximetry – Unexplained hypoxemia in the setting of a normal chest radiograph should raise the clinical suspicion for PE and prompt further evaluation. However, while often abnormal among patients suspected of having PE, ABGs can be normal in up to 18 percent of patients with PE [28]. However, abnormal gas exchange may be due to, and/or worsened by, underlying cardiopulmonary disease [29]. Common abnormalities seen on ABGs include one or more of the following [6,28,30] (see "Arterial blood gases"):

Hypoxemia (74 percent)

Widened alveolar-arterial gradient for oxygen (62 to 86 percent)

Respiratory alkalosis and hypocapnia (41 percent)

Hypercapnia, respiratory, and/or lactic acidosis are uncommon but can be seen in patients with massive PE associated with obstructive shock and respiratory arrest.

Abnormal oxygenation may be of prognostic value. As an example, patients with hypoxemia or room air pulse oximetry readings <95 percent at the time of diagnosis are at increased risk of complications, including respiratory failure, obstructive shock, and death [31]. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Outpatient anticoagulation'.)

Brain natriuretic peptide (BNP) – Elevated BNP has limited diagnostic value in patients suspected of having PE [32,33]. However, elevated BNP or its precursor, N-terminal (NT)-proBNP may be useful prognostically for risk stratification of patients diagnosed with acute PE. (See "Overview of acute pulmonary embolism in adults", section on 'Prognosis'.)

Troponin – Similarly, serum troponin I and T levels are useful prognostically but not diagnostically [34-38]. As markers of right ventricular dysfunction, troponin levels are elevated in 30 to 50 percent of patients who have a moderate to large PE [34,39] and are associated with clinical deterioration and death after PE. Troponin elevations usually resolve within 40 hours following PE, in contrast to the more prolonged elevation after acute myocardial injury [40]. (See "Overview of acute pulmonary embolism in adults", section on 'Prognosis'.)

D-dimer – The role of D-dimer in the diagnostic evaluation of suspected PE is discussed below. (See 'D-dimer' below.)

Electrocardiography — Electrocardiogram (ECG) abnormalities, although common in patients with suspected PE, are nonspecific [41-45]. The most common findings are tachycardia and nonspecific ST-segment and T-wave changes (70 percent) [7].

Abnormalities historically considered to be suggestive of PE (S1Q3T3 pattern, right ventricular strain, new incomplete right bundle branch block) are uncommon (less than 10 percent) [46,47]. ECG abnormalities that are associated with a poor prognosis in patients diagnosed with PE include [41,42,44]:

Atrial arrhythmias (eg, atrial fibrillation)

Bradycardia (<50 beats per minute) or tachycardia (>100 beats per minute)

New right bundle branch block

Inferior Q-waves (leads II, III, and aVF)

Anterior ST-segment changes and T-wave inversion

S1Q3T3 pattern

Chest radiograph — Nonspecific abnormalities on chest radiography are common (eg, atelectasis, effusion) in PE, but a normal chest radiograph can be seen in 12 to 22 percent of patients [6,7,48]. A chest radiograph is typically performed in most patients suspected of PE to look for an alternative cause of the patient's symptoms. It is also performed to determine eligibility for ventilation perfusion (V/Q) scanning (see 'Ventilation perfusion scan' below). However, it is not necessary if a CTPA is planned.

A Hampton's hump and Westermark's sign are rare but, when present, should raise the suspicion for PE [49]. Hampton's hump is a shallow, hump-shaped opacity in the periphery of the lung, with its base against the pleural surface and hump towards the hilum (image 1). Westermark's sign is the demonstration of a sharp cut-off of pulmonary vessels with distal hypoperfusion in a segmental distribution within the lung (image 2).

HEMODYNAMICALLY UNSTABLE PATIENTS — PE is stratified into massive, submassive, and low-risk based upon the presence or absence of hypotension and right ventricular dysfunction or dilation. This stratification is associated with mortality risk [50,51]. In the small percentage of patients with hemodynamic instability, either at presentation or during the course of their illness, the symptoms range from mild hypotension to overt obstructive shock. The initial approach should focus upon restoring perfusion with intravenous fluid resuscitation and vasopressor support (if needed), as well as oxygen supplementation and airway stabilization with intubation and mechanical ventilation (if needed).

In this population, diagnosis and therapy are often approached simultaneously. However, in this section, we focus on diagnosis; the definition of hemodynamic instability and the approach to therapy are discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Initial approach and resuscitation' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically unstable patients'.)

Hemodynamic stability restored following resuscitation — For patients in whom hemodynamic stability is restored following brief resuscitation (eg, for 15 minutes), we suggest the following approach:

High suspicion for PE – For patients in whom the suspicion for PE is high, we prefer immediate anticoagulation (provided there is no contraindication) and definitive diagnostic imaging, usually computed tomography pulmonary angiogram (CTPA). This approach is contingent upon prompt access to imaging and the presence of staff that can administer cardiopulmonary resuscitation (CPR) and/or empiric thrombolytic therapy in the event that the patient decompensates during testing.

Low or moderate suspicion for PE – For patients with a low or moderate suspicion of PE, the same approach to diagnosis and empiric anticoagulation should be used as for patients who are hemodynamically stable. (See 'Hemodynamically stable patients' below.)

Hemodynamically unstable despite resuscitation — For patients who remain hemodynamically unstable (eg, systolic pressure <90 mmHg for 15 minutes or longer or clear evidence of shock) despite adequate resuscitation, definitive testing is typically considered unsafe. In these circumstances, bedside lower extremity ultrasonography and transthoracic echocardiography may be used to obtain a presumptive diagnosis of PE. In this population of unstable patients, a presumptive diagnosis of PE may justify the administration of potentially life-saving therapies (eg, thrombolysis). (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically unstable patients'.) (Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically unstable despite resuscitative efforts.)

While bedside lower extremity compression ultrasonography does not diagnose PE, it is sufficient for the diagnosis of deep venous thrombosis (DVT), which is sufficient to initiate treatment. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'Point-of-care ultrasonography' and 'Lower-extremity ultrasound with Doppler' below.)

Similarly, the presence of new right ventricular strain or direct visualization of thrombus within the heart (ie, clot-in-transit) does not make a definitive diagnosis of PE but treatment should be initiated based upon these findings in an unstable patient (provided there is no contraindication). Although visualization of thrombus in a proximal pulmonary artery is diagnostic of PE, it is rare and generally only seen on transesophageal echocardiography. Early systolic notching of the pulsed wave Doppler waveform in the right ventricular outflow tract may be present in submassive or massive pulmonary embolism but further study is warranted before this sign can be routinely interpreted as conclusive evidence of PE [52]. (See 'Echocardiography' below.)

In many academic centers, the initial evaluation and resuscitation of hemodynamically unstable patients suspected as having PE are often performed in conjunction with pulmonary embolism response teams (PERTs). These teams are comprised of cardiothoracic surgeons, pulmonary and intensive care unit clinicians, cardiologists, emergency clinicians, and interventional radiologists [53-55]. In centers with limited resources (eg, without PERT or without bedside ultrasonography), the responding clinician must rely upon clinical judgment to assess the risk-benefit ratio of empiric anticoagulation and/or thrombolysis in the absence of definitive testing. (See 'Determining the pretest probability of pulmonary embolism' below.)

Treatment of hemodynamically unstable PE and the role of bedside ultrasonography in the evaluation of shock are discussed separately. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'Point-of-care ultrasonography' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically unstable patients'.)

HEMODYNAMICALLY STABLE PATIENTS — The majority of patients with PE are hemodynamically stable on presentation [8]. In this population of patients, sufficient time is available to adopt a systematic approach for the diagnosis of PE.

Overview — Several approaches for hemodynamically stable nonpregnant adult patients with suspected PE have been proposed [1-3,56-62]. Their purpose is to efficiently diagnose all clinically important PE while simultaneously avoiding the risks of unnecessary testing. We prefer an approach that selectively integrates clinical evaluation, three-tiered pretest probability (PTP) assessment, PE rule out criteria (PERC), D-dimer testing, and imaging (algorithm 1 and algorithm 2 and algorithm 3). Computed tomography pulmonary angiogram (CTPA) is the imaging modality of choice. However, algorithms that use a ventilation perfusion (V/Q) scan are appropriate when CTPA is contraindicated, not feasible, or inconclusive. (See 'Computed tomography pulmonary angiography' below and 'Alternate imaging approaches' below.) (Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically stable.)

Empiric anticoagulation while waiting for test results should be individualized according to the clinical suspicion for PE, the anticipated timing of definitive testing, and the risk of bleeding, the details of which are discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Empiric anticoagulation' and "Venous thromboembolism: Initiation of anticoagulation".)

Determining the pretest probability of pulmonary embolism — Whenever PE is suspected, the PTP for PE should be estimated by clinical gestalt assessment or calculated using a validated PTP score (eg, Wells score, Modified Wells score, or Modified Geneva score) [9,56,57,63-68]. Although gestalt estimates and calculating probability scores have comparable sensitivity when combined with D-dimer testing, meta-analyses suggest that probability scores may have higher specificity [9,68] and increase the diagnostic yield of CTPA [69].

Although use of Wells, Modified Wells (table 2) (calculator 1), or Modified Geneva score (table 3) (calculator 2) is acceptable, based upon extensive validation and our clinical experience, we prefer that the Wells criteria be applied and the score calculated to determine probability of PE into a three-tiered system of:

Low (score <2) (see 'Low probability of pulmonary embolism' below)

Intermediate (score 2 to 6) (See 'Intermediate probability of pulmonary embolism' below.)

High (score >6) (see 'High probability of pulmonary embolism' below)

Subsequent testing is dependent upon the likelihood of PE, which is discussed in the sections below. (See 'Computed tomography pulmonary angiography' below and 'Alternate imaging approaches' below.)

Wells criteria include the following (table 2) (calculator 1):

Clinical symptoms of deep vein thrombosis (DVT) (3 points)

Other diagnoses are less likely than PE (3 points)

Heart rate >100 (1.5 points)

Immobilization three or more days or surgery in previous four weeks (1.5 points)

Previous DVT/PE (1.5 points)

Hemoptysis (1 point)

Malignancy (1 point)

Despite validation of the Wells criteria, for unclear reasons, clinicians do not use them or use them incorrectly in up to 80 percent of patients [70,71]. In addition, they may not be as accurate in older or critically ill patients [66,72]. Wells criteria have best validated in outpatients presenting with suspected PE. However, one study of hospitalized patients, reported a sensitivity and specificity of 72 and 62 percent, respectively [73]; the addition of D-dimer to Wells criteria improved the sensitivity to 99 and reduced the specificity to 11 percent.

The Wells criteria can also be used to classify patients into a two-tiered system: patients are likely (score >4) or unlikely (score ≤4) to have PE. Although it has been validated and is equally as useful, we prefer to use the three-tiered classification of low, intermediate, and high probability since this classification allows D-dimer testing to be applied to both low- and intermediate-risk patients (score ≤6), further reducing the need for unnecessary testing. It can also be used to interpret results of V/Q scans more accurately.

A retrospective study compared the Wells score with the YEARS algorithm and found that the YEARS algorithm was more sensitive (97 versus 74 percent) but less specific (14 versus 34 percent) for the diagnosis of PE [74]. The YEARS algorithm is described below. (See 'D-dimer' below.)

Low probability of pulmonary embolism — For patients with a low probability of PE (eg, PTP <15 percent, Wells score <2), we apply the PERC (table 4) to determine whether or not diagnostic evaluation with D-dimer is indicated (algorithm 3). While some experts measure D-dimer in all low-risk patients, our preference to use PERC is based upon validity of this approach in this population, and the likely reduction (approximately 20 percent) of unnecessary testing (ie, D-dimer and imaging) associated with its use [75]. When the PERC rule is chosen, the following applies to patients for whom the clinician has determined that a diagnostic evaluation for PE is indicated (see 'PERC rule' below):

For patients who fulfill all eight PERC criteria, no further testing is required

For patients who do not fulfill all eight criteria, further testing with sensitive D-dimer measurement is indicated

In low-risk patients where PERC cannot be applied (eg, inpatients, critically-ill patients) or PERC is positive, D-dimer testing is indicated and the following applies (see 'D-dimer' below):

When the D-dimer level is <500 ng/mL (fibrinogen equivalent units), no further testing is required

When the D-dimer level is ≥500 ng/mL (fibrinogen equivalent units), diagnostic imaging should be performed, preferably with CTPA (see 'Computed tomography pulmonary angiography' below)

PERC rule — The PE rule out criteria (PERC) rule was designed to identify patients with a low clinical probability of PE in whom the risk of unnecessary testing outweighs the risk of PE [2,75-77] (see 'Low probability of pulmonary embolism' above). The PERC rule has eight criteria (table 4):

Age <50 years

Heart rate <100 beats/minute

Oxyhemoglobin saturation ≥95 percent

No hemoptysis

No estrogen use

No prior DVT or PE

No unilateral leg swelling

No surgery/trauma requiring hospitalization within the prior four weeks

In patients with a low probability of PE who fulfill all eight criteria, the likelihood of PE is sufficiently low that further testing is not indicated. Best illustrating the value of PERC is a crossover cluster-randomized noninferiority trial of 1916 emergency department (ED) patients with a low gestalt clinical probability of PE (ie, 15 percent probability of PE) that compared PERC with conventional assessment (ie, an evaluation that included measuring a D-dimer level to determine further testing) [78]. There was no difference in the rate of PE and only one patient in the PERC group (0.1 percent) developed PE during the three- month follow-up period, compared with none in the conventional group. The application of PERC resulted in a reduction in the proportion of patients undergoing CTPA (13 versus 23 percent) and also reduced the ED stay by 36 minutes. Another multicenter prospective cohort study of 8138 ED patients with a low clinical suspicion for PE reported that among those who fulfilled all of the eight criteria, only 15 (less than 1 percent) were diagnosed with DVT or PE within the subsequent 45 days [75]. Another study evaluated PERC in patients with a low probability of PE based upon the Wells criteria (score <2) (table 2) (calculator 1), in lieu of a gestalt estimate, and found a similarly high negative predictive value and sensitivity [79].

PERC is only valid in clinical settings (typically the ED) with a low prevalence of PE (<15 percent) [76]. In clinical settings with a higher prevalence of PE (>15 percent), the PERC-based approach has been shown to have a substantially poorer predictive value [76]. Thus, it should not be used in patients with an intermediate or high suspicion for PE or for inpatients suspected as having PE.

D-dimer — An elevated D-dimer alone is insufficient to make a diagnosis of PE, but a normal D-dimer can be used to rule out PE in patients with a low or intermediate probability of PE.

D-dimer testing is best used in conjunction with clinical probability assessment (table 2) (calculator 1):

For patients in whom the risk of PE is thought to be low, a normal D-dimer (<500 ng/mL [fibrinogen equivalent units]) effectively excludes PE, and typically no further testing is required. This includes patients who have had a prior PE and those with a delayed presentation and hospitalized patients [22,73,80]. In contrast, an elevated D-dimer (>500 ng/mL [fibrinogen equivalent units]) should prompt further testing with diagnostic imaging. (See 'Low probability of pulmonary embolism' above.)

For most patients in whom the risk of PE is thought to be intermediate, a normal D-dimer (<500 ng/mL [fibrinogen equivalent units]) also effectively excludes PE, and typically no further testing is required. However, some experts believe that a subset of patients in the intermediate risk category (eg, those in the upper zone of the intermediate range [eg, Wells score 4 to 6 or Modified Geneva sore 8 to 10] or patients with limited cardiopulmonary reserve) should undergo imaging based upon the higher probability of PE in these patients since the sensitivity of D-dimer is not as good.

For patients in whom the risk of PE is thought to be high, a normal D-dimer is not as helpful for excluding the diagnosis and does not need to be performed. While a negative D-dimer result does reduce the likelihood of PE in this population, it does not reduce it sufficiently to rule out the diagnosis, with some data suggesting a prevalence of PE of 5 percent or more in those with a high pretest probability and a negative D-dimer [81-85] (see 'High probability of pulmonary embolism' below). These patients should undergo diagnostic imaging, preferably with CTPA.

We prefer "sensitive D-dimer" testing that uses quantitative or semiquantitative newer generation immunoturbidimetric, latex-agglutination-based, or rapid enzyme-linked immunosorbent assays (ELISA). These assays are preferred because of their high sensitivity, and the fact that accurate results are available quickly (10 to 30 minutes) so that prompt decisions regarding imaging can be made. For these assays, a level ≥500 ng/mL (fibrinogen equivalent units) is usually considered positive, and <500 ng/mL (fibrinogen equivalent units) is considered negative [81,86].

In contrast, early generation D-dimer assays (eg, qualitative rapid ELISA, first-generation latex, and erythrocyte agglutination) are less accurate. In a meta-analysis of 108 studies, when compared with other assays for D-dimer testing, the preferred assays (eg, semiquantitative rapid ELISAs) were associated with a higher sensitivity (96 versus 90 percent) and negative predictive value (98 versus 95 percent) [81]. The sensitivity of D-dimer is lower in patients with subsegmental PE compared with patients who have large main, lobar, or segmental PE (53 versus 93 percent) [87].

While D-dimer assays are highly sensitive, their specificity is low, usually between 40 and 60 percent. D-dimer results are often falsely positive, and the proportion of false positive results increases with certain clinical conditions and any acute or inflammatory process (eg, age >50 years, recent surgery or trauma, acute illness, pregnancy or postpartum state, rheumatologic disease, renal dysfunction [estimated glomerular filtration rate <60 mL/min/1.73 m2]), and sickle cell disease (table 5) [26,88-92].

Adjusted D-dimer — Although high-sensitivity D-dimer testing is preferred, adjusted D-dimer levels based on certain criteria have been proposed and may be considered as an alternative in patients with a low probability or low intermediate probability for PE. They should not be used in those with high-probability or intermediate-high-probability for PE.

Age-adjusted D-dimer – D-dimer levels rise with age such that using the traditional cutoff value of <500 ng/mL (fibrogen equivalent units) results in reduced specificity of D-dimer testing in older patients (>50 years), a population in whom PE is common. Several studies report its use [2,61,93-98] with the most commonly used formula for age adjustment as:

Age (if over 50 years) x 10 = cutoff value in ng/mL (fibrinogen equivalent units)

One meta-analysis of six trials reported that in patients unlikely to have PE by the Wells criteria (score ≤4 (table 2) (calculator 1), compared with a negative fixed level D-dimer, a negative age-adjusted D-dimer was associated with a 5 percent increase in the proportion of patients in whom imaging can be safely withheld [97]. A major trial that supported its role is discussed below (ADJUST-PE). (See 'Computed tomography pulmonary angiography' below.)

D-dimer and YEARS – Alternate D-dimer cut-offs have also been used. In one prospective multicenter study, 3465 patients with suspected PE from an outpatient setting underwent D-dimer testing and an assessment of pretest probability using the YEARS criteria [99]. The YEARS criteria include three items from the Wells score: clinical signs of DVT, hemoptysis, and PE as the most likely diagnosis, all scored as a yes or no. PE was excluded in patients with zero YEARS items and a D-dimer level <1000 ng/mL, and patients with ≥1 YEARS item and a D-dimer <500 ng/mL. All other patients underwent CTPA. Using this algorithm, 13 percent of patients were diagnosed with PE. Among those in whom PE was excluded, 0.6 percent had symptomatic PE confirmed at three-month follow-up [99], a rate that was similar to that reported in studies that utilize fixed D-dimer level testing <500 ng/mL [56]. It was estimated that this algorithm would result in a 14 percent reduction in the number of CT scans performed, compared with using the Wells rule and a fixed D-dimer level <500 ng/mL. In this study, using age-adjusted D-dimer had no additional value to this algorithm [100], although subsequent studies have found additive value in using a combined approach. A similar multicenter prospective observational study of 1134 emergency department patients suspected as having PE and referred for imaging per the treating physician's discretion, reported a potential 14 percent reduction in those imaged using YEARS criteria and a negative D-dimer (<1000 ng/mL for YEARS negative patients and <500 ng/mL for YEARS positive patients) [101].The sensitivity and specificity of this strategy were 93 and 55 percent respectively. This algorithm has been externally validated for the safety of ruling out PE but caution was advised in patients with no YEARS items and a D-dimer level <1000 ng/mL but above the age-adjusted cutoff [102].

D-dimer adjusted to clinical probability (PEGeD) – In a prospective study of 2017 outpatients with suspected PE, patients with a low clinical probability (calculated per the Wells score (calculator 1)) plus a negative D-dimer <1000 ng/mL and patients with a moderate clinical probability and a negative D-Dimer <500 ng/mL did not undergo CTPA (or anticoagulation) [103]. All other patients underwent imaging. During a three month follow-up, no patients with a low or moderate clinical probability plus a negative D-dimer (<1000 ng/mL and <500 ng/mL, respectively) developed symptomatic venous thromboembolism (VTE). Using the PEGeD protocol, 34 percent of patients were imaged compared with an estimated 52 percent, had the traditional parameters (low clinical pretest probability plus a D-dimer <500 ng/mL) been used to rule out PE (ie, a 17 percent reduction in patients imaged). These findings are consistent with protocols that utilize D-dimer adjusted to YEARS criteria (see above bullet) [99,101]. However, these results mostly apply to patients in the low-probability pretest group since only 40 patients in this study had a moderate pretest probability. In addition, whether this protocol applies to inpatients or populations with a high prevalence of PE is also unknown.  

PERC-positive patients plus YEARS and age-adjusted D-Dimer – One noninferiority trial randomized PERC-positive patients with a low clinical probability of PE and patients with an intermediate probability for PE to further triage using YEARS criteria plus age-adjusted D-dimer (intervention group) or to age-adjusted D-dimer alone (control group) and compared VTE outcomes at three months [104]. In patients with zero YEARS criteria plus a D-dimer <1000 ng/mL and in patients with one or more YEARS criteria plus a D-dimer level less than the age-adjusted threshold, PE was considered to be excluded and no imaging was performed. Imaging was performed if patients did not meet these criteria. Over 1200 patients were analyzed and the PE rate was 7.3 percent. The YEARS plus D-dimer strategy resulted in a 10 percent reduction in patients who underwent chest imaging and a 1.6-hour reduction in the emergency department (ED) stay. There was also a nonsignificant reduction in the rate of VTE at three months (one versus five patients; 0.15 percent versus 0.8 percent; adjusted difference, –0.64 percent, 97.5% CI, –∞ to 0.21 percent). While encouraging, the complexity of this protocol may not be practical in busy setting such as the ED and could theoretically introduce error. In addition, it underestimates the value of CT in identifying other etiologies for a patient's presenting symptoms.

Comparing protocols – One meta-analysis compared diagnostic strategies for ruling out PE including those that use clinical prediction rules, standard D-Dimer cutoffs (ie, 500 ng/mL), and adjusted D-Dimer (eg, age-adjusted or adjusted according to clinical pretest probability [eg, YEARS]) [105]. Protocols that used pretest probability models and adjusted D-Dimer were more efficient, as defined by the proportion of individuals considered to have PE excluded (ie, more cases of PE are excluded without imaging). However, they also had the highest failure rate as defined by the three-month rate of VTE after exclusion of PE without imaging (ie, more cases of VTE are missed). In addition, protocols did not perform uniformly across all subgroups, with the lowest efficiency observed in those who were 80 years of age or older and in patients with cancer.

Data discussing age-adjusted D-dimer and its role in patients with suspected DVT are provided separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'D-dimer' and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'D-dimer'.)

Intermediate probability of pulmonary embolism — For most patients in whom the suspicion for PE is intermediate, a sensitive D-dimer level should be measured (algorithm 2). (See 'D-dimer' above.)

When the D-dimer level is <500 ng/mL (fibrinogen equivalent units), no further testing is typically required. However, some experts will proceed with diagnostic imaging in select patients. For example, imaging may be considered in patients who have limited cardiopulmonary reserve (ie, patients in whom PE would not be well tolerated) or those in whom the clinical probability of PE was in the upper zone of the intermediate range (eg, a Wells score of 4 to 6 or a Geneva score of 8 to 10).

When the D-dimer level is ≥500 ng/mL (fibrinogen equivalent units), diagnostic imaging should be performed, preferably with CTPA. (See 'Computed tomography pulmonary angiography' below.)

D-dimer — Data that support the value of measuring D-dimer levels in patients in whom the clinical suspicion is intermediate are discussed above. (See 'D-dimer' above.)

High probability of pulmonary embolism — For most patients in whom the probability of PE is high or in whom the suspicion is low or moderate and the D-dimer level is elevated, CTPA should be performed (algorithm 1).

When imaging is indicated, CTPA is the imaging modality of choice. V/Q scan is reserved for patients in whom the CTPA is contraindicated (eg, history of moderate or severe contrast allergy, high risk of contrast nephropathy [estimated glomerular filtration rate <30 mL/min/1.73 m2], or inability to tolerate computed tomography [CT] scanning due to class 2 or 3 obesity or difficulty lying flat). V/Q may also be indicated when CTPA is inconclusive, or when additional testing is needed, such as when the clinical suspicion of PE remains high despite negative imaging. Hypotension and advanced heart failure may limit the circulation of IV contrast and increase the likelihood of an indeterminate CTPA [106].

CTPA – For patients in whom CTPA is performed, the following applies (see 'Computed tomography pulmonary angiography' below):

A positive CTPA showing a filling defect confirms the diagnosis of PE. Treatment of PE including subsegmental PE is discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults".)

A negative CTPA indicates that the likelihood of PE is low. Typically, no further testing is required, unless inadequate imaging is suspected (eg, the contrast bolus is poorly timed and pulmonary arteries are inadequately opacified) or for another reason clinical suspicion for PE remains high after negative CTPA. (See 'Alternate imaging approaches' below.)

An inconclusive CTPA result may necessitate alternate imaging, such as V/Q scanning or lower-extremity venous ultrasonography. (See 'Alternate imaging approaches' below.)

V/Q scan – For patients in whom a V/Q scan is performed, management is dependent upon the interpretation of the scan in the context of the pretest clinical probability for PE. Although the Wells criteria were developed after the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study [5], it is appropriate to use Wells to stratify risk (table 2 and table 6) for the purposes of interpretation (see 'Ventilation perfusion scan' below):

In patients with a normal V/Q scan and any clinical probability, no further testing is necessary.

In patients with a low-probability V/Q scan and low clinical probability (eg, Wells score <2 (table 2) (calculator 1)), no further testing is necessary.

In patients with a high-probability V/Q scan and high clinical probability (eg, Wells score >6 (table 2) (calculator 1)), immediate treatment is indicated. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults".)

All other combinations of V/Q scan results and clinical pretest probabilities are indeterminate (inconclusive), and further testing is required. (See 'Other imaging' below.)

Computed tomography pulmonary angiography — For most patients with suspected PE, CTPA, also called chest CT angiogram with contrast, is the first-choice diagnostic imaging modality because it is sensitive and specific for the diagnosis of PE, especially when incorporated into diagnostic algorithms. Alternate diagnoses may also be discovered using this modality [107]. The imaging technology is widely available and, in most settings, the exam can be performed on an urgent or emergent basis. In some cases, if contraindications to CTPA are present but can be readily resolved (eg, premedication for a contrast allergy) and alternate imaging such as V/Q scanning is not feasible, CTPA may be performed after a short delay (eg, 8 to 12 hours) with consideration for empiric anticoagulation while waiting. (See 'Alternate imaging approaches' below and "Prevention of contrast-induced acute kidney injury associated with computed tomography" and "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography", section on 'Prevention'.)

CTPA imaging protocol — CTPA examination acquires thin (≤2.5 mm) section volumetric images of the chest after a bolus administration of intravenous contrast that is timed precisely for maximal enhancement of the pulmonary arteries. A multidetector (≥16 detector rows) CT scanner is required to achieve sufficient diagnostic performance. Primary axial and multiplanar reformations (commonly in the coronal plane) of the pulmonary arteries are routinely reviewed. For optimal image quality, the patient should be able to hold still and hold their breath for about 30 seconds. A chest CT with contrast not performed as a CTPA but for other indications may incidentally detect pulmonary emboli but is not an adequate exam for excluding suspected PE [107].

A CTPA result may be indeterminate for a number of reasons. The most common include patient motion, large body habitus, beam hardening artefacts from metallic foreign bodies, and suboptimal enhancement of the pulmonary artery usually due to abnormal cardiac output [106]. Repeat CTPA for more definitive results may be worthwhile if the factor causing poor image quality can be mitigated (eg, patient more capable of cooperating with positioning and breath-holding instructions). However, the risk of renal impairment due to repeated doses of intravenous contrast should be considered when determining whether and when to repeat CTPA. Repeat imaging is unlikely to prove useful if CTPA is nondiagnostic from factors such as scanner technology, body habitus, or indwelling metallic foreign bodies.

CTPA may be relatively contraindicated in patients with a history of moderate to severe iodinated contrast allergy or renal insufficiency (eGFR <30 mL/min per 1.73 m2). The risk of these contraindications must be weighed against the clinical importance of performing the CTPA examination and the availability of alternative imaging approaches (eg V/Q scan). If clinically feasible, CTPA should be delayed for premedication for history of allergy or intravenous hydration for renal insufficiency. (See "Prevention of contrast-induced acute kidney injury associated with computed tomography" and "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography", section on 'Prevention'.)

The approximate effective radiation dose from CTPA is 10 mSv and varies depending upon patient size, scanner type, and imaging protocol. In young (age <30 years) adults or pregnant patients who are undergoing multiple chest CT exams, minimizing cumulative radiation dose may be a consideration in opting for alternative imaging techniques including ventilation perfusion scanning, venous ultrasound, magnetic resonance pulmonary angiogram (MRPA), if the necessary technology and expertise are available. (See 'Magnetic resonance pulmonary angiography' below.)

CT venogram (CTV) of the lower extremities and pelvis with contrast to evaluate for DVT is not routinely performed concurrently with the CTPA. CTV, when added to CTPA, may marginally improve diagnostic yield. However, the added effective radiation dose from CTV is approximately 6 mSv, thereby significantly increasing the radiation dose over the entire patient population [108,109].

Results interpretation — Support for our preference for CTPA-based algorithms is derived from a prospective, multicenter cohort study (Christopher study) of 3306 patients with clinically suspected PE [56]. Patients were from an inpatient or outpatient setting and categorized according to the modified Wells score as PE "likely" (score >4) or PE "unlikely" (score ≤4) (table 2) (calculator 1). Patients classified as PE unlikely underwent sensitive D-dimer testing; PE was considered excluded when the D-dimer level was <500 ng/mL (fibrinogen equivalent units). PE unlikely patients who had a D-dimer level ≥500 ng/mL (fibrinogen equivalent units) and PE likely patients underwent CTPA. When the CTPA confirmed PE, patients were anticoagulated; when it excluded PE or was inconclusive (rarely), patients were not treated. At three months follow-up, the rates of venous thromboembolism during follow-up were low, as evidenced by the following:

Among 1028 untreated patients in whom PE was excluded by clinical assessment plus D-dimer testing, there was one DVT (0.1 percent), four nonfatal PE (0.4 percent), and no fatal PE.

Among 1436 untreated patients in whom PE was excluded by CTPA, there were eight DVT (0.6 percent), three nonfatal PE (0.2 percent), and seven fatal PE (0.5 percent).

Among 674 treated patients in whom PE was detected by CTPA, there were six DVT (0.9 percent), three nonfatal PE (0.4 percent), and 11 fatal PE (1.6 percent).

A similarly designed prospective, multicenter study of 3346 patients with suspected PE in an emergency department setting reported comparable results using age-adjusted D-dimer cutoffs (ADJUST-PE) [61]. In ADJUST-PE, patients were classified as PE unlikely or likely. Those who were PE unlikely underwent age-adjusted D-dimer testing (age [if over 50] multiplied by 10 [eg, normal D-dimer at 60 years is <600 ng/mL]). When the age-adjusted value was negative, no further testing was performed. All other patients underwent CTPA. When CTPA was positive, PE was confirmed and when CTPA was negative, PE was excluded. Patients with inconclusive CTPA results or in whom CTPA could not be performed had additional imaging (eg, V/Q scan, serial ultrasound [US], pulmonary angiogram) to diagnose or exclude PE. At three months follow-up, rates of venous thromboembolism were low, as evidenced by the following:

Among the 1141 untreated patients in whom PE was excluded by clinical assessment plus age-adjusted D-dimer testing, there were only two cases (0.2 percent) of nonfatal PE. Compared with using a fixed D-dimer level of <500 ng/mL, use of age-adjusted cutoffs resulted in a 12 percent increase in the number of patients in whom a diagnosis of PE could be safely excluded without further imaging.

Among the 673 untreated patients ≥75 years in whom PE was excluded by clinical assessment plus age-adjusted D-dimer testing, there were no thromboembolic events.

Among the 1481 untreated patients in whom PE was excluded by CTPA, there was one DVT (0.1 percent), four cases of nonfatal PE (0.2 percent), and two indeterminate events.

Age-adjusted D-dimer assessments are being increasingly used with significant institutional variation.

Diagnostic performance — Most studies report that CTPA is >90 percent sensitive and specific for the diagnosis of PE especially in the low and intermediate clinical risk groups. The highest sensitivities (≥96 percent) are reported when CTPA is combined with a moderate to high clinical probability assessment for PE, but lower when combined with a low clinical probability of PE [110-115]. The PIOPED II study reported that the sensitivity and specificity of multidetector CTPA was 83 (90 percent when combined with high suspicion) and 96 percent, respectively, using catheter-based pulmonary angiography as the reference standard [115]. However, numerous cohort studies that use technically advanced scanners and specific CTPA protocols have since consistently reported a low incidence (<2 percent) of PE in patients with low to moderate clinical suspicion and a negative CTPA [116-120]. Nevertheless, there is a risk of PE in those with a negative CTPA and a high clinical suspicion for PE (up to 5 percent when a ≤64 detector row multidetector CT [MDCT] is used), such that further testing (eg, lower-extremity venous ultrasonography) may need to be considered [121].

CTPA is traditionally considered most accurate for the detection of large, main, lobar, and segmental PE, and less accurate for the detection of smaller, peripheral subsegmental PE (SSPE). Newer scanners with increased resolution have increased the detection of smaller emboli [122-125]. As an example, one systematic review that included 2657 patients reported improved detection of SSPE by multidetector row CTPA compared with single-detector row CTPA (9.4 versus 4.7 percent) [122]. However, in some cases of isolated SSPE, repeat or additional testing may need to be performed. Management of SSPE is discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Patients with subsegmental PE'.)

One commonly cited benefit of CTPA is its ability to detect alternative pulmonary abnormalities that may explain the patient's presenting symptoms and signs (image 3) [126-129]. In one observational study, 9 percent of CTPA examinations confirmed PE, while 33 percent identified an alternative cause of the patient's symptoms [128]. In another retrospective review of 641 patients who underwent CTPA for suspected PE, an alternate diagnosis was discovered in 14 percent of patients who did not have PE, and 15 percent of these findings required immediate attention [129].

Alternate imaging approaches — When imaging is indicated and CTPA cannot be performed or is inconclusive, we recommend V/Q scanning. In some cases, CTPA can be reconsidered if it was previously contraindicated but subsequently becomes feasible (eg, when renal function improves or after premedication for a contrast allergy). (See 'CTPA imaging protocol' above.)

Ventilation perfusion scan — V/Q scanning is mostly reserved for patients in whom CTPA is contraindicated or inconclusive, or when additional testing is needed.

A normal chest radiograph is usually required prior to V/Q scanning. Scans performed on patients with abnormal chest radiographs more likely to result in false positives as the images rarely appear normal or low probability of PE in such patients. The patient is asked to lie still for 30 to 60 minutes for a V/Q scan. The approximate effective radiation dose is less than 2 mSv.

Support for our approach using V/Q scanning is based upon the following data:

In PIOPED, V/Q scans were reported as one of the following [5]:

Normal

Low-probability PE

Intermediate-probability PE

High-probability PE

The risk of PE was reported in combination with pretest probability assessment (table 6) (see 'Determining the pretest probability of pulmonary embolism' above):

Patients with a low clinical probability and a normal or low-probability V/Q scan had a less than 4 percent chance of having a PE while those with an intermediate and high probability scan had a 16 and 15 percent chance of having PE.

Patients with a high clinical probability and a high-probability scan had a 96 percent chance of having a PE. Those with normal scan had a 0 percent chance of having PE, and those with a low- or intermediate-probability scan had a 40 and 66 percent chance of having PE, respectively.

Patients with an intermediate probability of PE and a high-probability scan had an 88 percent chance of having PE while all other combinations had probability of PE that ranged from 6 to 28 percent.

Most patients have indeterminate scans, which is the major limitation of V/Q scanning since an indeterminate scan is insufficient to either confirm or exclude the diagnosis of PE, thereby necessitating additional testing.

One systematic review evaluated over 7000 patients from 25 prospective studies, 23 of which included V/Q scan-based algorithms [130]. Three diagnostic strategies were identified as safely excluding patients with PE over a three-month follow-up:

Among patients with a low clinical probability of PE in whom PE was excluded by normal D-dimer levels, PE occurred in less than 3 percent.

Among patients in whom clinical probability combined with D-dimer assessment was inconclusive, a normal perfusion scan (Q scan) safely excluded PE.

Among patients with an intermediate-probability V/Q scan, holding therapy was safe until further testing was performed (eg, catheter-based pulmonary angiography or serial lower-extremity venous ultrasonography).

Although perfusion scanning alone is sometimes performed in limited cases, data to support its use in the diagnosis of PE are limited.

Portable V/Q scans have been described for use in intensive care unit patients, although their accuracy has not been compared with CTPA [131].

Other imaging — When neither CTPA nor V/Q scanning can be performed or are inconclusive, we prefer noninvasive testing with lower extremity compression ultrasonography with Doppler to evaluate for coexisting DVT. If the cumulative radiation dose in a young or pregnant patient is a concern, and if the necessary technology and expertise is available, MRPA could substitute for CTPA but is less sensitive and more dependent on the experience of the technologist doing the scan. Catheter-based pulmonary angiography is more invasive and slightly less sensitive than CTPA, and is usually reserved for patients where a concurrent therapeutic intervention is planned. Occasionally, echocardiography can be used when a rapid or presumptive diagnosis is needed in emergent circumstances but does not directly diagnose PE.

Lower-extremity ultrasound with Doppler — A new diagnosis of DVT in the setting of symptoms consistent with PE is highly suggestive, although not definitively diagnostic, of PE. As such, Doppler ultrasonography can be used as an initial test in the evaluation of suspected PE, as positive results can justify initiating anticoagulant treatment. However, because of the low sensitivity of Doppler ultrasonography in this setting [132,133], it is not sufficient to rule out PE and may be most useful for patients suspected of having a PE but in whom definitive imaging (eg, CTPA, V/Q scanning) is contraindicated, indeterminate, or likely to be delayed.

We suggest the following approach when Doppler ultrasonography is used in patients with suspected PE in whom chest imaging is indeterminate or contraindicated:

If lower-extremity Doppler ultrasonography is positive, patients can be treated (usually anticoagulation).

If Doppler ultrasonography is negative and the clinical suspicion for PE is low or intermediate (calculator 1) (table 2), it is generally considered safe to withhold anticoagulation and monitor for DVT with serial ultrasonography until chest imaging can be performed (eg, after treatment of contrast allergy) [130,134]. However, it is unknown whether the same approach can be used in patients with poor cardiopulmonary reserve (ie, patients that would not tolerate a PE); in these patients, empiric anticoagulation may be appropriate. The optimal frequency of serial exams is unknown and at the discretion of the clinician. (See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)", section on 'Surveillance with serial ultrasound'.)

The safety of serial monitoring for DVT was illustrated in a prospective study of 874 patients with suspected PE, who had adequate cardiopulmonary reserve and a low or intermediate-probability V/Q scan [134]. Six serial lower-extremity venous ultrasounds were performed over a two-week period, and anticoagulation was administered only if the ultrasonography was positive. At three months, fewer than 3 percent of patients developed PE.

If Doppler ultrasonography is negative and the suspicion for PE is high, further imaging and/or or empiric anticoagulation should be attempted. The rationale for this approach is that ultrasonography may be negative in the setting of PE, either because thrombus has travelled to the lung or because clots in the calf and/or pelvic veins are not readily detected by ultrasonography [135,136].

Whether proximal vein ultrasonography (which detects proximal vein DVT) or whole leg ultrasonography (which detects proximal and calf vein DVT) should be performed is unknown. Although some experts consider whole leg ultrasonography as ideal, the choice is often institutionally-determined.

Catheter-based pulmonary angiography — Pulmonary angiography, in which contrast is injected under fluoroscopy via a catheter introduced into the right heart, was the historical gold standard for the diagnosis of PE. With the widespread emergence of CTPA, this procedure is infrequently used and reserved for rare circumstances for patients with a high clinical probability of PE, in whom CTPA or V/Q scanning is nondiagnostic and in whom a diagnosis determines an important clinical decision (eg, an intervention) (image 4). Pulmonary angiography seems to be less accurate than CTPA and its diagnostic performance is highly variable and dependent on the experience of the operator [130,137]. Consequently, catheter-based pulmonary angiography is most often performed in patients in whom concurrent therapy is planned since it can combine diagnosis with therapeutic interventions aimed at clot lysis (eg, catheter-directed embolectomy and/or thrombolysis); its use in this context is also dictated by local expertise. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Embolectomy'.)

As the historical gold standard, the sensitivity and specificity of catheter-based pulmonary angiography for the diagnosis of PE has not been formally evaluated. However, one retrospective analysis of 20 cases from PIOPED II suggested that it may be less sensitive than CTPA for the detection of small emboli [137,138]. Nonetheless, in patients with a negative angiogram, the risk of subsequent symptomatic embolization is low (<2 percent) [5,130].

Although pulmonary angiography is generally well tolerated in the presence of hemodynamic instability [139,140], the mortality of the procedure is approximately 2 percent but <1 percent for those who are hemodynamically stable [139,140]. Morbidity occurs in approximately 5 percent of patients and is usually related to catheter insertion, contrast reactions, cardiac arrhythmia, or respiratory insufficiency [26,139,141]. Radiation exposure depends upon the length and complexity of the procedure, but is typically greater than that from CTPA [142,143].

Magnetic resonance pulmonary angiography — MRPA is not recommended as a first-line test for the diagnosis of PE but may be an imaging option for diagnosis of PE in patients in whom neither CTPA nor V/Q scan can be performed. Potential advantages of MRPA are that no ionizing radiation is involved and the examination can be combined with MR venography in the same sitting. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Alternative imaging'.)

The patient is asked to lie still in a magnetic resonance (MR) scanner for >30 minutes and intravenous gadolinium is administered. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging", section on 'Indications for giving contrast with MRI'.)

Most importantly, in order to avoid a nondiagnostic result from inadequate image quality, MRPA should only be performed at sites with the necessary technology and expertise. Technically inadequate images can result from patient motion, scanner technology, and the timing the gadolinium contrast bolus [144-148].

MRPA was studied prospectively in 371 adults with suspected PE. Among the 75 percent of patients who had technically adequate images, MRPA alone showed a sensitivity and specificity of 78 percent and 99 percent, respectively [145]. Among the 48 percent of patients with technically adequate images, MRPA and MR venography showed a sensitivity and specificity of 92 percent and 96 percent, respectively. Two additional prospective studies reported a similarly poor sensitivity for MRPA alone [144,145,149]. Sensitivity was greater for emboli located in the main/lobar and segmental vessels (100 and 84 percent, respectively), compared with subsegmental vessels (40 percent; ie, emboli that should be easily detected on CTPA).

Echocardiography — Echocardiography can diagnose PE when thrombus is visualized in the proximal pulmonary arteries, although this is a rare phenomenon. Although not definitive, the diagnosis of PE is supported on echocardiography by the presence of clot in the right heart or new right heart strain. The demonstration of any clot or new strain in hemodynamically unstable patients with suspected PE may be useful if a rapid or presumptive diagnosis is required to justify the emergency use of thrombolytic therapy [150-154]. However, in most cases, particularly those who are hemodynamically stable, echocardiography is generally considered insensitive (since abnormalities are frequently absent in patients with PE) and nonspecific (since right ventricle [RV] abnormalities can be seen in other conditions including chronic pulmonary disease, pulmonary hypertension, and right ventricular infarction); in addition, the demonstration of new right heart strain may not be evident in the absence of a prior echocardiogram. Although echocardiography has limited value diagnostically, it is most useful for prognostic purposes in patients with confirmed PE (eg, new RV strain and RV thrombus are poor prognostic indicators), the details of which are discussed separately. (See "Echocardiographic assessment of the right heart" and "Overview of acute pulmonary embolism in adults", section on 'Prognosis'.)

Approximately 30 to 40 percent of patients with PE have echocardiographic abnormalities indicative of RV strain or pressure overload [155-157] and data suggest that there is direct correlation between the extent of RV dysfunction and the degree of perfusion defects on lung scans [152,153]. RV findings include:

Increased RV size

Decreased RV function

Tricuspid regurgitation

Abnormal septal wall motion

McConnell's sign

Decreased tricuspid annular plane systolic excursion (TAPSE)

Regional wall motion abnormalities that spare the right ventricular apex (McConnell's sign) are insensitive (77 percent) for the diagnosis of PE but, in those who demonstrate this sign, it may be used to distinguish patients with RV strain from acute PE from those with pulmonary hypertension, who tend to have global RV dysfunction [158]. In general, RV strain is insensitive and nonspecific with one meta-analysis reporting a sensitivity of 53 percent and specificity of 61 percent [154].

Additional echocardiographic findings suggestive of PE that are uncommon but more worrisome for PE include:

RV thrombus – Among patients with intracardiac thrombus, one retrospective study reported that 35 percent had PE [159], while another registry-based study reported that among patients with known PE, approximately 4 percent have an RV thrombus [160].

Pulmonary artery thrombus – Thrombus in the pulmonary arteries or main branches of the pulmonary arteries may be seen on transesophageal echocardiography but is rare.

Investigational — Dual energy CT, single photon emission CT (SPECT), and multiorgan ultrasound are being developed as imaging exams that could accurately and more safely diagnose PE.

Dual energy computed tomography – Dual energy CT could reduce the amount of iodinated contrast needed to perform CTPA examinations and increase the sensitivity for PE by imaging an iodine map, which serves as a surrogate for lung perfusion [161]. Large cohort studies have not been yet reported.

SPECT – Technological advances in single photon emission CT ventilation and perfusion imaging may allow for accurate diagnosis of PE without iodinated contrast administration and it has a lower radiation dose than CTPA (unless SPECT-CT is performed). It may increase detection of smaller pulmonary emboli. Preliminary studies suggest that SPECT is as sensitive as CTPA and more sensitive than V/Q scanning [162-164]. The optimal scanning technique is unknown (perfusion SPECT, V/Q SPECT, SPECT or V/Q SPECT with non-enhanced CT) and its use may be limited to centers that have the technological expertise to perform it.

Multiorgan ultrasound – Multiorgan ultrasonography (ultrasound of the heart, lung, and lower extremity) was prospectively examined in 357 patients suspected of having PE (Wells score >4) [165]. A sensitivity and a specificity of 90 and 86 percent, respectively, was noted when CTPA was used as a reference standard. Rare case reports describe the demonstration of thrombus in central pulmonary arteries on endobronchial ultrasonography [166-168].

PATIENTS WITH SUSPECTED RECURRENT PULMONARY EMBOLISM — The approach to patients with suspected recurrent PE (days to years) should be the same as for a first suspected event with some minor differences:

In those who are hemodynamically stable, although the D-dimer level is less likely to be negative in those with recurrence, it can still be useful in a limited proportion (<15 percent) to distinguish those who should have imaging from those who should not. (See 'D-dimer' above.)

When feasible, prior imaging should be obtained in patients with suspected recurrence (but should not delay treatment, when indicated). Many patients will present with similar symptoms to their initial PE, not all of which are due to new thrombus, thus, it is useful to distinguish symptoms that are due to new thrombus. However, the interpretation of repeat imaging may be difficult since thrombus can migrate with time and the rates of clot resolution are variable [169,170]. As examples:

In a cohort of 79 patients with acute PE receiving anticoagulant therapy, complete clot resolution occurred in 40 percent of patients within one week, 50 percent within two weeks, 73 percent within four weeks, and 81 percent by four weeks or longer [169]. Resolution was quicker in larger (main and lobar) pulmonary arteries compared with smaller (segmental and subsegmental) vessels, particularly during the first week.

Another cohort of 111 patients with acute PE reported similar results, but thrombus resolved more quickly in peripheral compared with larger pulmonary arteries [170].

Differential diagnosis and management of suspected recurrence is discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Monitoring and follow-up' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Management of recurrence on therapy'.)

DIAGNOSIS — A diagnosis of PE is made radiographically by one of the following modalities using the following criteria:

Computed tomographic pulmonary angiography (CTPA) or magnetic resonance pulmonary angiography (MRPA) – A filling defect in any branch of the pulmonary artery (main, lobar, segmental, subsegmental) that becomes evident after contrast enhancement is diagnostic of PE (image 5 and image 6) [115]. Indeterminate or nondiagnostic scans are reported when a filling defect is not clearly visualized (eg, embolus in a small peripheral pulmonary artery, poor contrast enhancement, image degradation by motion or metallic beam hardening artefact). (See 'Computed tomography pulmonary angiography' above and 'Magnetic resonance pulmonary angiography' above.)

Ventilation perfusion (V/Q) scanning – A segmental or subsegmental perfusion defect with normal ventilation are diagnostic of PE. Images are interpreted as high, intermediate, or low probability of PE or normal. A normal scan and a low probability scan in the setting of low clinical probability of PE are sufficient to exclude PE. A high-probability V/Q scan and high probability of PE confirms PE. All other combinations of V/Q results and clinical probability are nondiagnostic. Practice guidelines regarding the performance and interpretation of V/Q scans are available at the Society of Nuclear Medicine on lung scintigraphy [171]. (See 'Ventilation perfusion scan' above.)

Catheter-based pulmonary angiography – The demonstration of a filling defect or abrupt cutoff of a vessel is diagnostic of an embolus (image 4). Indeterminate or nondiagnostic scans are reported when the filling defect is not clearly visualized. (See 'Catheter-based pulmonary angiography' above.)

Echocardiography is rarely diagnostic of PE but a presumptive diagnosis may be made in patients who are hemodynamically unstable so that life-saving therapy can be administered. (See 'Echocardiography' above and 'Hemodynamically unstable patients' above.)

Lower-extremity proximal vein compressive ultrasound (US) demonstrating deep venous thrombosis (DVT) is not diagnostic of PE but can be used to justify treatment in emergent settings or when other testing cannot be obtained. (See 'Lower-extremity ultrasound with Doppler' above.)

PE is sometimes seen on a standard contrast-enhanced computed tomography (CT) performed for an alternate reason or discovered pathologically in a resected pulmonary lobe. In these cases, dedicated pulmonary artery or leg vein imaging to diagnose residual PE or DVT may be indicated.

Once a diagnosis is made, further risk stratification of the patient to determine the prognosis should be performed. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Prognosis'.)

DIFFERENTIAL DIAGNOSIS — For patients who present with signs and symptoms of PE, the major competing diagnoses include heart failure, pneumonia, myocardial ischemia or infarction, pericarditis, acute exacerbations of chronic lung disease, pneumothorax, and musculoskeletal pain. Computed tomography pulmonary angiography (CTPA) may identify many of these alternative diagnoses.

The differential diagnosis of PE depends upon the presenting signs and symptoms, many of which are discussed separately:

Dyspnea – Dyspnea that is abrupt in onset or disproportionate to the patient's underlying lung function, or dyspnea that occurs with hypoxemia, hemoptysis, and/or pleuritic chest pain may favor a diagnosis of PE. (See "Overview of acute pulmonary embolism in adults" and "Approach to the patient with dyspnea" and "Approach to the adult with dyspnea in the emergency department".)

Chest pain – Acute chest pain, especially pain that is pleuritic in nature, is highly suspicious for PE, but may also be due to other etiologies such as pneumonia, pericarditis, pleuritis, and rib fracture.

Hemoptysis – Hemoptysis that occurs with pleuritic pain and hypoxemia should prompt consideration of acute PE, but can also be secondary to pneumonia or heart failure (often frothy and pink). (See "Evaluation of nonlife-threatening hemoptysis in adults".)

Leg pain and swelling – Unilateral leg swelling should raise the suspicion for PE in association with deep vein thrombosis (DVT), while bilateral swelling may be more supportive of heart failure. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Differential diagnosis'.)

Syncope – Syncope in patients without a clear precipitant should raise suspicion for PE [18]. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Approach to the adult patient with syncope in the emergency department".)

Hypoxemia – Hypoxemia (partial pressure of oxygen in arterial blood on room air <80 mmHg [10 kPa]) in the setting of a normal chest radiograph, or hypoxemia that is disproportionate to the chest radiograph appearance, should prompt consideration of PE as well as the following alternate diagnoses:

Other pulmonary vascular diseases (eg, chronic venous thromboembolism, pulmonary hypertension, anatomic shunt, arteriovenous malformations) (see "Epidemiology, pathogenesis, clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension" and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults" and "Pulmonary arteriovenous malformations: Epidemiology, etiology, and pathology in adults")

Interstitial lung disease (eg, lymphangioleiomyomatosis, Langerhans cell histiocytosis) (see "Approach to the adult with interstitial lung disease: Clinical evaluation")

Congenital heart disease (eg, shunt, septal defect, left ventricular outlet obstruction, chronic mitral stenosis, Eisenmenger syndrome) (see "Evaluation and prognosis of Eisenmenger syndrome")

Lower-airway disease (eg, pneumonia, asthma, bronchiectasis, acute or chronic bronchitis, foreign body aspiration, tracheobronchomalacia) (see "Evaluation of wheezing illnesses other than asthma in adults")

Upper-airway disease (eg, paradoxical vocal cord dysfunction, upper-airway obstruction syndromes, tumors) (see "Inducible laryngeal obstruction (paradoxical vocal fold motion)" and "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Clinical features')

Neuromuscular disease (eg, hypoventilation, drugs, multiple sclerosis, diaphragmatic paralysis, myasthenia gravis) (see "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation")

Tachycardia – Unexplained tachycardia, especially in a patient with risk factors for PE, should prompt clinicians to consider PE, but can be associated with other diagnoses, including cardiac arrythmia, sepsis, hypovolemia, drugs, and toxins. (See "Sinus tachycardia: Evaluation and management".)

Shock – Unexplained shock should prompt the clinician to consider acute PE. Although the presence of shock and a normal chest radiograph increases the suspicion for PE, this can be found in many forms of distributive shock (eg, anaphylaxis, shock from drugs and toxins, neurogenic shock, myxedema coma). (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'Differential diagnosis'.)

The differential diagnosis of common conditions that mimic PE include the following:

Heart failure – The combination of dyspnea and leg swelling due to heart failure may mimic PE. Evidence of pulmonary edema may be supported by crackles and chest radiography. While brain natriuretic peptide elevation can support heart failure, this can also be seen in acute PE. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis".)

Pneumonia – Fever, consolidation on chest imaging, and leukocytosis may favor infection over PE, but can also be the presenting features of an acute lobar pulmonary infarct secondary to PE, particularly as it evolves over the first few days or weeks. The presence of risk factors for PE, persisting symptoms or poor response to antibiotics, or abrupt onset of new symptoms during the course of subacute illness should prompt the clinician to investigate for PE. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults" and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults" and "Nonresolving pneumonia".)

Myocardial ischemia or infarction – Cardiac chest pain is typically not pleuritic and evidence of myocardial ischemia or infarction can be seen on electrocardiography (ECG). While troponin elevation can suggest cardiac chest pain, this can also be seen in acute PE. (See "Diagnosis of acute myocardial infarction".)

Pericarditis – The pain of pericarditis can be pleuritic and therefore mimic PE. The presence of a viral prodrome, pre-existing inflammatory disease, and electrocardiographic findings of ST elevation may increase the likelihood of pericarditis. (See "Acute pericarditis: Clinical presentation and diagnosis".)

Exacerbation of underlying chronic lung disease – Patients with chronic lung disease often present with dyspnea. Conversely, PE can complicate acute pulmonary diseases illness (eg, emphysema, pneumonia). Thus, the presence of another diagnosis does not completely exclude the possibility of PE. Wheezing is uncommon in PE, and may suggest an exacerbation of pre-existing lung disease such as asthma or chronic obstructive pulmonary disease. However, hypoxemia or respiratory distress out of proportion to obstructive symptoms or wheezing should prompt consideration of PE. (See "COPD exacerbations: Management".)

Pneumothorax – While acute pleuritic chest pain and dyspnea due to pneumothorax may mimic PE, pneumothorax should be apparent on chest imaging. (See "Pneumothorax in adults: Epidemiology and etiology" and "Treatment of secondary spontaneous pneumothorax in adults".)

Vasculitis Unexplained dyspnea, pleuritis, and hemoptysis can be presenting symptoms of both PE and pulmonary vasculitis. The presence of an interstitial pattern on chest radiograph in a patient with an underlying rheumatologic condition (eg, scleroderma) may distinguish vasculitis from PE. (See "Overview of and approach to the vasculitides in adults", section on 'Differential diagnosis'.)

Musculoskeletal pain – Acute chest wall pain may mimic the pleuritic pain of PE. However, in the absence of a clear history of injury, musculoskeletal pain should be considered a diagnosis of exclusion when PE remains on the differential diagnosis. (See "Evaluation of the adult with chest pain in the emergency department".)

COVID-19 — COVID-19 is a risk factor for the development of thrombosis. Details regarding hypercoagulability in patients with COVID-19 are provided separately. (See "COVID-19: Hypercoagulability".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Pulmonary embolism (blood clot in the lungs) (The Basics)")

Beyond the Basics topics (see "Patient education: Pulmonary embolism (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Clinical features – Pulmonary embolism (PE) has a wide variety of presenting features, ranging from no symptoms to shock or sudden death. The most common presenting symptom is dyspnea followed by chest pain (classically but not always pleuritic) and cough. However, many patients, including those with large PE, have mild symptoms or are asymptomatic. (See 'Clinical presentation' above.)

Initial tests – In patients with symptoms consistent with PE, tests including electrocardiography (ECG), chest radiography, brain natriuretic peptide (BNP) and troponin levels should be performed. However, these tests are neither sensitive nor specific for the diagnosis of PE, and are most useful for confirming the presence of alternative diagnoses or providing prognostic information in the event that PE is diagnosed. (See 'Laboratory tests' above and 'Electrocardiography' above and 'Chest radiograph' above.)

Hemodynamically unstable patients – (See 'Hemodynamically unstable patients' above.) (Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically unstable despite resuscitative efforts.)

For patients with a high clinical suspicion for PE who are hemodynamically unstable and successfully resuscitated, immediate anticoagulation and definitive diagnostic imaging is preferred. (See 'Hemodynamic stability restored following resuscitation' above.)

For patients with a low or moderate suspicion of PE who are successfully resuscitated, the same approach to diagnosis and empiric anticoagulation should be used as for patients who are hemodynamically stable. (See 'Hemodynamically stable patients' above.)

For patients who remain unstable despite resuscitation, bedside echocardiography and lower extremity compression ultrasonography (US) with Doppler of the leg veins can be used to obtain a rapid or presumptive diagnosis of PE (visualization of thrombus or new right heart strain) to justify the administration of potentially life-saving therapies, including thrombolytic agents. (See 'Hemodynamically unstable patients' above and 'Electrocardiography' above.)  

Hemodynamically stable patients – For patients with suspected PE who are hemodynamically stable, we suggest an approach that selectively integrates clinical evaluation, three-tiered pretest probability testing (eg, clinical gestalt or the Wells criteria (calculator 1) (table 2)), PE rule out criteria (PERC), D-dimer, and imaging. Computed tomographic pulmonary angiography (CTPA), also called chest computed tomography (CT) angiogram with contrast, is the preferred imaging exam (algorithm 1 and algorithm 2 and algorithm 3) (see 'Hemodynamically stable patients' above) (related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically stable):

In patients with a low clinical probability of PE (eg, <15 percent, Wells score <2), the PERC (table 4) should be applied. Patients who fulfill all eight criteria do not need additional testing. For patients who do not fulfill PERC criteria or in whom PERC cannot be applied, further testing with sensitive D-dimer measurement is indicated; no imaging is required when the D-dimer level is normal (<500 ng/mL [fibrinogen equivalent units]), while imaging is indicated in those with a positive D-dimer. (See 'Low probability of pulmonary embolism' above.)

A positive D-dimer can be defined as ≥500 ng/mL (fibrinogen equivalent units) or a value higher than the age-adjusted or pretest probability adjusted (eg, YEARS) threshold. Adjusted D-dimer levels based on certain criteria have been proposed and may be considered as an alternative in patients with a low probability (or low intermediate probability for PE). They should not be used in those with high-probability or intermediate-high-probability for PE. (See 'Adjusted D-dimer' above.)  

In patients with an intermediate clinical probability of PE (eg, Wells score 2 to 6), we prefer sensitive D-dimer testing to determine whether or not diagnostic imaging is indicated. Patients with a negative D-dimer do not need imaging while those with a positive D-dimer should have chest imaging. However, some experts proceed directly to diagnostic imaging in select patients (eg, those with limited cardiopulmonary reserve or those in the upper zone of the intermediate range such as a Wells score of 4 to 6). (See 'Intermediate probability of pulmonary embolism' above.)

In patients with a high clinical probability of PE (eg, Wells score >6), we prefer diagnostic imaging with CTPA. A positive result confirms the diagnosis of PE while a negative result excludes it in nearly all cases. (See 'High probability of pulmonary embolism' above and 'Computed tomography pulmonary angiography' above.)

CTPA acquires thin (≤2.5 mm) section volumetric images of the chest after a bolus administration of intravenous contrast that is timed precisely for maximal enhancement of the pulmonary arteries. A multidetector row (≥16 detectors rows) CT scanner is required to achieve sufficient diagnostic performance. A chest CT with contrast not performed as a CTPA but for other indications is not an adequate exam to exclude suspected PE. (See 'CTPA imaging protocol' above.)

Alternate imaging approaches

Ventilation perfusion (V/Q) scanning – For patients with suspected PE in whom CTPA is contraindicated, unavailable, or inconclusive, V/Q scanning is the alternative imaging exam. V/Q scan results, reported as high-, intermediate- or low-probability for PE, or normal, should be interpreted in conjunction with clinical suspicion. A high-probability V/Q scan and high clinical probability is sufficient to confirm PE. A normal scan or a low-probability scan in the setting of low clinical probability of PE can also be used to rule out PE. All other combinations of V/Q results and clinical probability are nondiagnostic. (See 'Hemodynamically stable patients' above and 'Ventilation perfusion scan' above.)

Other testing – For patients in whom both CTPA and V/Q scanning are contraindicated, unavailable, or inconclusive, we prefer noninvasive testing with lower-extremity compression ultrasonography with Doppler (although not diagnostic of PE). (See 'Lower-extremity ultrasound with Doppler' above.)

Diagnosis – A diagnosis of PE is made radiographically based upon CTPA, magnetic resonance pulmonary angiogram (MRPA), or catheter-based pulmonary angiography by the demonstration of a filling defect in any branch of the pulmonary artery. With V/Q scanning, a high-probability scan with high clinical probability confirms PE. (See 'Diagnosis' above.)

Differential diagnosis – The differential diagnosis of PE includes many other entities that present similarly with dyspnea, chest pain, hypoxemia, leg pain and swelling, tachycardia, syncope, and shock. Other competing diagnoses including heart failure, myocardial ischemia, pneumothorax, pneumonia, and pericarditis may be distinguished on electrocardiographic, echocardiographic, laboratory, and chest radiographic testing. However, PE can coexist with these conditions and, therefore, the presence of an alternate diagnosis does not completely exclude the diagnosis of PE. (See 'Differential diagnosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Charles Hales, MD, now deceased, who contributed to an earlier version of this topic review.

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Topic 8261 Version 111.0

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