Pulmonary embolism (PE), a form of venous thromboembolism (VTE), is the third leading cause of cardiovascular death in Western countries, and its prevalence has increased over time [1–4]. Approximately 75 to 269 cases of VTE occur per 100,000 individuals yearly in Western Europe, North America, Australia, and southern Latin America [5]. In Korea, the annual incidence of VTE was 53.7 cases per 100,000 person-years in 2018, increasing from 32.8 in 2014, exhibiting a tendency to gradually increase over years [6]. Additionally, the annual incidence rate of PE also increased with age, with an approximately 26-fold higher rate in individuals aged ≥ 75 years than in those aged < 35 years. These data demonstrate the importance of PE in the aging population of Korea as well as Europe, further suggesting that PE will increasingly burden healthcare systems globally in the coming years [7]. PE contributes to approximately one-third of this VTE burden. Although prompt diagnosis and appropriate treatment have reduced all-cause and PE-related mortality, acute PE remains a potentially lethal disease, with a current mortality of approximately 5% to 7% [8,9].

Herein, we illustrate a typical case of acute PE that a clinician may encounter in routine clinical practice. In this case, a 33-year-old man with a history of myotonic dystrophy presented with worsening dyspnea for 5 days. His initial blood pressure was 108/64 mmHg, heart rate was 120/min, respiratory rate was 25/min, and body temperature was 36.5°C. On physical examination, lung sounds were clear, and no cardiac murmur was found. The initial chest radiograph was normal (Fig. 1A). However, the electrocardiogram demonstrated sinus tachycardia and an S wave in lead I (S1), Q wave in lead III (Q3), T wave inversion in lead III (T3), and precordial leads V1–3 (Fig. 1B). We performed echocardiography to evaluate the cause of dyspnea. Echocardiography showed a D-shaped left ventricle (LV) (Fig. 1C), McConnell’s sign (Fig. 1D), linear thrombus in the main pulmonary artery (Fig. 1E), echocardiographic signs of the increased pulmonary arterial systolic pressure (Fig. 1F and 1G), and decreased right ventricular (RV) contractility assessed by tricuspid annular plane systolic excursion (TAPSE) (Fig. 1H). After the echocardiographic examination, we suspected the presence of acute PE and confirmed the diagnosis using contrast-enhanced computed tomography (CT) of the chest. After subcutaneous injection of low-molecular-weight heparin for 5 days, the patient was treated with oral warfarin therapy. Although echocardiographic examination was not used to confirm the diagnosis in this case, it provided diagnostic clues regarding the patient’s clinical presentation.

Echocardiography is the most used imaging modality for evaluating and managing acute PE. Besides to give clues about other etiologies for chest pain or dyspnea, echocardiography can be used in the early risk stratification and impact management strategies in patients with acute PE. In addition, it can be used to predict prognosis in these patients. Throughout this review, we discuss the role of echocardiography in diagnosing and predicting outcomes in patients with signs or symptoms of PE. Further, we describe the impact of echocardiography on risk stratification and management strategies of PE.

Bedside echocardiography is indicated for diagnosing suspected acute PE in high-risk patients in the recent guidelines for the diagnosis and management of acute PE by the European Society of Cardiology (ESC, class I, level of evidence C) [10]. In addition, echocardiographic parameters are valuable markers for early risk stratification of patients with acute PE [10]. The presence of RV dysfunction assessed by echocardiography can be an indication for thrombolysis, particularly in patients with hemodynamic instability [10,11]. The American Heart Association guidelines indicate the presence of RV dysfunction in patients with RV dilatation (RV to LV end-diastolic diameter ratio [RV/LV ratio] > 0.9) or RV systolic dysfunction on echocardiographic studies [11]. However, in the ESC and American Society of Hematology guidelines, thrombolytic therapy is not indicated in patients with acute PE who are hemodynamically stable and do not have RV dysfunction [10,12].

Although computed tomography pulmonary angiography (CTPA) with contrast enhancement and lung ventilation/ perfusion scan are the gold standard for diagnosing acute PE [10], echocardiography plays a key role in its diagnosis. As the most available, and noninvasive diagnostic modality that does not require contrast agents or radiation, echocardiography is a feasible imaging modality for diagnosing acute PE.

Acute PE causes RV pressure overload, potentially leading to RV systolic dysfunction. Echocardiography can provide several clues to rule in or rule out acute PE, including regional wall motion abnormality in patients with acute myocardial infarction and dissecting aortic flaps in patients with acute aortic dissection in an emergency setting. We searched all published articles in English focused on the calculation of diagnostic accuracy of transthoracic echocardiography in the PubMed (National Library of Medicine, www.pubmed.gov) database. We selected 13 studies reporting quantitative data and reanalyzed diagnostic power. Table 1 shows the diagnostic power of several echocardiographic signs for acute PE. An illustration showing parameters found in patients with PE is presented in Fig. 2.

Echocardiography can be useful in PE diagnosis, particularly in patients for whom performing CT is impossible or difficult [45]. Although echocardiography is not recommended in the diagnostic work-up for hemodynamically stable patients with PE, it can be included in the evaluation of suspected high-risk PE [45].

Considering this, echocardiography in pregnant women may be useful for PE diagnosis because it has no known adverse effect on the fetus. PE is a leading cause of pregnancy-related mortality in developed countries, accounting for 20% of maternal deaths in high-income countries [46]. VTE risk is higher in pregnant women than in non-pregnant women of similar age; it increases during pregnancy and reaches a peak during the post-partum period [47]. The most common PE symptoms include dyspnea (73%), pleuritic chest pain (66%), cough (37%), and hemoptysis (13%). The abrupt onset of pleuritic chest pain may be the first unique symptom. However, accurate clinical suspicion or VTE diagnosis during pregnancy is challenging because of the overlap of signs and symptoms between physiologic changes during pregnancy and the development of PE. The pregnant patient must undergo specific diagnostic tests to establish or exclude PE diagnosis because routine laboratory findings are not specific for confirming the diagnosis. Because radiation exposure during pregnancy can be associated with fetal teratogenic and oncogenic effects, conventional pulmonary angiography or standard-dose CT should be avoided, particularly in the first trimester [45]. Patients with chronic kidney disease (CKD) also have a high-risk of VTE due to activation of procoagulants, decreased anticoagulants, or decreased fibrinolytic activity [48]. A clinical diagnosis of acute PE in patients with CKD is frequently considered; however, the diagnostic approach is challenging. Current guidelines recommend CTPA as the gold standard for an imaging test. However, CTPA is prohibited for use in patients with severe renal impairment due to the increased risk of contrast-induced complications [10]. Thus, for these special populations, a D-dimer test and duplex ultrasound of the lower extremities play essential roles in PE diagnosis. Lung ventilation/perfusion scan, a lower-radiation and contrast medium-sparing procedure, may preferentially be applied if an imaging test is necessary, but it may not be used in an emergency setting [49]. Echocardiography can provide signs that may help in the differential diagnosis of shock; thus, the absence of echocardiographic findings of RV pressure overload can exclude PE as the cause of hemodynamic instability. Moreover, echocardiographic findings suggesting causes other than acute PE can help exclude the need for CT. However, a low-dose CT or ventilation/perfusion scan should be used to distinguish PE in patients with unequivocal echocardiographic signs of RV pressure overload.

Acute PE mortality risk levels are conventionally divided into high, intermediate (high/low), and low levels. This stratification can be achieved using four diagnostic tools: the patient’s hemodynamic state, Pulmonary Embolism Severity Index (PESI) score, echocardiographic RV systolic dysfunction parameters, and cardiac markers (troponin). The ESC guidelines classify patients with acute PE into the following categories: (1) high-risk, defined as the presence of shock or persistent hypotension; (2) intermediate-risk, defined as not at high-risk, and a simplified PESI (sPESI) score ≥ 1; and (3) low-risk, defined as the absence of hypotension and an sPESI score of 0 [50]. Risk stratification is essential for allocating each patient to the appropriate treatment and considering more aggressive initial treatments, such as thrombolytic therapy or surgical embolectomy [51]. The presence of RV systolic dysfunction is a poor prognostic factor and represents a more advanced pathophysiologic PE stage. The assessment of RV systolic function is one of the crucial factors for the risk stratification and further management [52]. Although many methods exist for evaluating RV systolic function, no single measurement is accepted as the gold standard. The ESC risk stratification approaches use alternate imaging modalities, such as echocardiography and CT angiography, to assess RV systolic function. However, in hemodynamically stable patients with acute PE, further risk assessment is required based on clinical imaging, cardiac biomarkers (mostly related to RV function and myocardial injury), and the presence of comorbidities. Thus, current risk stratification has focused on identifying low-risk PE in hemodynamically stable patients. Of the 17 prognostic models of acute PE, PESI, and sPESI are the most widely validated and are now included in the risk classification of the ESC guidelines [53,54]. A recently updated prognostic model showed improvement in the prognosis of acute PE by adding one or more clinical-, biological-, and imaging-based markers of RV systolic dysfunction and myocardial injury to the existing models [55].

The standard treatment for most patients with PE in the acute phase is anticoagulation and thrombolytic therapy [10]. Recently, more effective therapies and interventions, such as greater use of anticoagulants, thrombolysis, and surgical embolectomy in practice, have contributed to the reduction in mortality and PE recurrence.

Because thrombolytic therapy dissolves thrombi in the pulmonary arterial system, it lowers pulmonary arterial pressure and improves RV systolic function more rapidly than anticoagulation only in selected patients with acute PE [56,57]. In patients with high-risk PE, thrombolysis was associated with a reduction in mortality (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.45 to 0.97) [58]. All treatment guidelines recommend thrombolysis as the initial treatment of choice for patients with acute PE who are hemodynamically unstable. Thus, early identification of RV systolic dysfunction in high-risk patients with acute PE is essential in promptly deciding whether to administer thrombolytic therapy [59]. Many critically ill patients cannot undergo more advanced imaging; therefore, bedside echocardiography should be performed at an emergency department or intensive care unit to identify RV systolic dysfunction [60,61].

The role of thrombolysis is unclear in patients with intermediate-risk acute PE. Several large randomized controlled trials have investigated the impact of thrombolytic treatment. The Pulmonary Embolism Thrombolysis (PEITHO) trial compared systemic thrombolysis plus anticoagulation with anticoagulation alone in the largest trial involving 1,005 adult patients with intermediate-risk PE. The incidence of death or hemodynamic decompensation was 2.6% in the group receiving tenecteplase group; this value was much lower than the 5.6% in the group receiving heparin (OR, 0.44; 95% CI, 0.23 to 0.87; p = 0.02) [62]. Although thrombolytic therapy was associated with a significant reduction in the risk of hemodynamic decompensation or collapse, there was an increased risk of bleeding, including major extracranial bleeding (6.3% vs. 1.2% in heparin alone) and hemorrhagic stroke (2.4% vs. 0.2% in heparin alone). Furthermore, thrombolytic therapy showed no reduction in overall mortality, persistent exertional dyspnea or functional limitation, and chronic thromboembolic pulmonary hypertension on long-term follow-up (median duration, 38 months) in the PEITHO trial (709 of 1,006 initially randomized patients) [63]. Therefore, current guidelines do not recommend routine primary reperfusion treatment in patients with intermediate-risk PE [64,65]. “Rescue” thrombolysis should be reserved for these patients if they develop signs of hemodynamic instability despite anticoagulant treatment. Although echocardiographic evidence of RV dysfunction is not a compelling indication for systemic thrombolysis even in intermediate-high-risk patients, there has been an overall uptrend in the use of cardiac imaging in hemodynamically stable patients with PE over the past decade [66]. Because of its easy availability, low procedural cost and risk, and potential for guiding appropriate early management, echocardiography has been used increasingly in non-massive PE at the time of admission [67].

Acute PE is the third leading cause of cardiovascular death, and its prevalence is increasing. Echocardiography has been validated for early risk stratification of patients presenting with acute PE and impacts management strategies. Despite decades of research, the role of echocardiography in diagnosing and predicting outcomes of acute PE remains under-estimated. The use of CTPA has facilitated early diagnosis in patients with suspected PE. However, echocardiography is the most available, noninvasive, and feasible imaging option (before performing CTPA) for patients with suspected PE.

Echocardiography has high specificity in diagnosing suspected PE in patients with adequate risk. Thus, it is helpful as a rule in test in the initial diagnosis of acute PE. Echocardiography may be particularly useful at the bedside in the emergency department or intensive care unit for patients who cannot undergo other confirmatory studies, especially those who are in the most critical condition. In addition, it can be a useful option in pregnant patients suspected of having acute PE. More effective therapies and interventions have contributed to reducing mortality and recurrence of acute PE in the last decade. Thrombolytic therapy is the initial treatment of choice in hemodynamically unstable patients with acute PE. Thus, echocardiography is widely used to identify RV dysfunction in high-risk patients with massive PE. For low-risk hemodynamically stable patients, echocardiography rarely yields additional prognostic information. Current guidelines do not recommend echocardiography as part of the diagnostic work-up in non-high-risk patients. However, the presence of RV systolic dysfunction is a poor prognostic factor and represents a more advanced pathophysiologic PE stage. RV dysfunction detected using echocardiography was associated with an increased risk of short-term mortality, even in hemodynamically stable patients with acute PE. Although echocardiography is not recommended for diagnostic work-up in hemodynamically stable patients with PE, echocardiographic assessment of RV systolic function is now widely recognized as a valuable tool for prognostic assessment of hemodynamically stable patients in current clinical practice. Furthermore, a recently updated prognostic model showed that specific echocardiographic RV dysfunction markers have the potential to improve prognosis beyond existing risk models. Furthermore, there has been an overall uptrend in cardiac imaging in the last decade, particularly echocardiography, even in patients with hemodynamically stable PE. Extensive validation and impact studies are needed to guide appropriate patient selection for echocardiography use in hemodynamically stable PE.