The Diagnostic Value of Bedside Echocardiography and Lower Extremity Blood Vessels in Acute Pulmonary Embolism.

Objective: The study aimed to evaluate the value of bedside echocardiography (TTE) and lower extremity blood vessels in diagnosis and prognosis of acute pulmonary embolism (APE).
Methods: A retrospective study was performed on 53 patients with APE diagnosed by CT pulmonary angiography (CTPA) (systemic systolic blood pressure was >90 mmHg at time of consultation, and systemic systolic blood pressure decreased by <40 mmHg compared with basic value in those with hypertension). All patients underwent TTE examination before treatment. The high-risk factors, clinical manifestations, laboratory tests, and prognosis were retrospectively analyzed.
Results: The rate of PE-related deterioration (cardiopulmonary resuscitation, tracheal intubation, cardiogenic shock, and death) within 14 days of hospitalization in RVD was 28%, and mortality rate (sudden death) was 20%, compared with non-RVD (both 0%). TTE examination showed that RVD as a predictor of pulmonary embolism-related death had a sensitivity of 100%, a specificity of 58%, a positive predictive value of 20%, and a negative predictive value of 100%. Conclusions: (1) TTE has increasingly shown obvious advantages in diagnosis of APE. It can detect direct or indirect signs of pulmonary embolism, confirm diagnosis or suspected diagnosis, and noninvasively and dynamically observe hemodynamic changes of heart in patients with acute PTE before and after treatment.. (2) The PE-related exacerbation rate (28%) or mortality (20%) of APE patients in normotensive with RVD was higher without RVD (0%). RVD is an independent predictor of poor prognosis in normotensive acute PTE. TTE tests allow people to identify people at risk of early death. The short-term prognosis of patients without RVD was better (14 days).

1. Introduction

Acute pulmonary embolism (APE) refers to a series of clinical and pathophysiological syndromes caused by endogenous or exogenous emboli through venous return and impacted in the pulmonary artery and its branches, resulting in obstruction of tissue blood supply. Acute pulmonary embolism (APE) is the third most fatal cardiovascular system disease after acute coronary syndrome and aortic dissection. Mortality rate and other characteristics, and its incidence have characteristics of increasing year by year. Filipiak-Strzecka, Kasprzak, and Lipiec [1] show that the incidence of pulmonary embolism (pulmonary embolism, PE) in the United States is 0.29% to 0.78%. The annual incidence of PE in Europe ranges from 0.1% to 0.2%, while mortality rate is as high as 34%. 59% of dead patients are undiagnosed before death, which shows that it has a high rate of misdiagnosis and missed diagnosis. Golshani and Sharafsaleh [2] showed that the annual average number of diagnoses gradually increased from 3 cases to 20.6 cases. Köse et al. [3] showed that the total incidence rate was 0.1%, and incidence rate increased year by year, from 0.03% to 0.14%. The mortality rate of APE is high, and prognosis varies greatly. About one-fourth of patients have sudden death as clinical manifestation. Morrone and Morrone [4] show that the case fatality rate in 10 years before 1988 showed an upward trend, and the case fatality rate in 10 years after 1988 showed a downward trend, and the total case fatality rate was 7%–60%. Xie et al. [5] showed that the all-cause mortality rate of patients with PE was 11.4% within 2 weeks and rose to 17.4% within 3 months. Sethi et al. [6] showed that 30% to 45% of patients who died were PE patients. Falster et al. [7] showed that 3-, 5-, and 10-year mortality rates of patients with thromboembolic pulmonary hypertension were 8.4%, 28.7%, and 53.8%, respectively. Banerjee and Mora [8] showed that 11% of APE patients died within 1 hour of onset. Therefore, an important factor to reduce the fatality rate of PE is to improve its early diagnosis rate.

At present, patients with acute pulmonary embolism are stratified according to comprehensive evaluation of clinical symptoms, laboratory examinations, and imaging examinations. The clinical manifestations of acute pulmonary embolism are diverse, with poor specificity and high misdiagnosis rate [9]. Biological indicators are highly sensitive in evaluating low- and intermediate-risk patients. Among imaging examinations, due to special anatomical position, complex geometry, and load dependence of right ventricle, echocardiography has obvious advantages over other examination methods in evaluating right ventricular function in patients with pulmonary embolism. The advantages of echocardiography compared with other imaging examinations are that it is fast, economical, and easy to operate, and important advantage is noninvasive. Ultrasound examination of PE, including lower extremity deep vein ultrasound and echocardiography, has several different imaging modalities such as M-mode ultrasound, two-dimensional ultrasound, and Doppler ultrasound [10]. There are two bedside and transesophageal exploration methods by echocardiography, which can find direct and indirect signs of PE. Direct signs are probing of thrombus in the pulmonary artery or left and right pulmonary arteries, bedside ultrasound imaging is blurred, and actual emboli are rarely seen during examination, and transesophageal echocardiography gradually replaces bedside ultrasound, especially in critically ill patients [11]. In the process of cardiopulmonary resuscitation, this method is direct, simple, and does not delay rescue time, and sensitivity and specificity of diagnosing central PE can reach 80–90%; indirect signs include right ventricular and pulmonary artery dilatation, right ventricular wall motion weakened, abnormal ventricular septal motion, increased tricuspid regurgitation flow velocity, and other manifestations of increased right heart load. Some foreign authors believe that decreased right ventricular contractility caused by overload of right ventricle caused by other reasons generally does not affect apical segment of right ventricular free wall, and PE mostly has abnormal myocardial systolic function in this segment, and diagnosis is based on this sign [12]. The sensitivity of PE is 77% and specificity is 90%, so it is specific for diagnosis of PE. In addition, echocardiography has important differential and diagnostic value for identifying sudden dyspnea, chest pain, circulatory failure, and other diseases suspected of PE, and excluding other related diseases, such as myocardial infarction, aortic dissection, and cardiac tamponade. If echocardiography shows that right heart is overloaded, wall motion is weakened, and there are signs of pulmonary hypertension, PE will be suggested or highly suspected. Because PE and DVT are considered to be different manifestations or different stages of same disease, it is found that DVT can explain the cause of PE, thereby indirectly supporting diagnosis of PE and providing future prevention and treatment work (such as vena cava filter implantation) in accordance with [13]. Ultrasound has advantages of simplicity, rapidity, noninvasiveness, and bedside operation, and it can also display changes of heart shape and function. Methods and more and more literatures suggest us that ultrasonography has been added to noninvasive technical means of diagnosing pulmonary embolism.

Combined with acute pulmonary embolism clinical symptom score and related laboratory test results and echocardiography to evaluate right heart function, it can provide better early diagnosis and treatment of pulmonary embolism disease and reduce mortality rate. At same time, it provides an important basis for management of echocardiography for risk stratification in patients with acute pulmonary embolism. This paper retrospectively analyzes clinical data of pulmonary embolism, evaluates diagnostic value of TTE for normotensive APE, and evaluates prognosis according to combination of various indicators of TTE.

2. Materials and Methods

2.1. Objects

A retrospective study of 53 patients with acute pulmonary embolism who were admitted to our hospital from January 2016 to November 2021 and were diagnosed by CT pulmonary angiography (CTPA) (25 cases in right ventricular dysfunction and 28 in right ventricular function normal) was eligible for inclusion in this study.

2.2. The Inclusion Criteria Are as Follows

The diagnosis of pulmonary embolism is based on the 2001 Guidelines for Diagnosis and Treatment of Pulmonary Thromboembolism of Respiratory Disease Branch of Chinese Medical Association (draft).

Systemic systolic blood pressure >90 mmHg at time of consultation, and if combined with hypertension, systemic systolic blood pressure decreased by <40 mmHg compared with basic value

2.3. Exclusion Criteria

The exclusion criteria includes chronic pulmonary thromboembolism (right ventricular free wall thickness >5 mm by TTE).

2.4. Detection and Observation Indicators

2.4.1. Clinical Manifestations and General Information

The following are clinical manifestations and general information: gender, age, respiratory rate, dyspnea, chest pain, cough, hemoptysis, palpitations, syncope, pulse, cyanosis, jugular vein filling, tricuspid murmur, blood pressure at visit, past medical history (hypertension, diabetes, etc.), coronary heart disease, previous history of lower extremity phlebitis or DVT/PE, cerebral hemorrhage, cerebral infarction, malignant tumor, recent surgery, family history of venous thromboembolism, etc.

2.5. Laboratory Examination

Blood gas analysis (PaO2, PH, PCO2, and (A − a)DO2), D-dimer, and myocardial markers (Tn- or Tn-T) were performed at time of enrollment. Arterial blood gas analysis is the most objective indicator to judge the relationship between respiratory failure and acid-base imbalance. Blood gas analysis can adequately determine which conditions warrant blood gas evaluation. Ventilation (PaCO2, provides the basis for oxygen inhalation or ventilator-assisted breathing), acid-base balance (pH and PaCO2, such as heart failure and renal failure, severe diabetes, severe infection, alcohol-related problems), oxygen and status (PaO2 and Sa02), and the ability of blood to transport oxygen (PaO2, Hb02, totalHb, and erythropoiesis disorders) are indicators of severe respiratory and pulmonary diseases. Asthma COPD respiratory failure requires monitoring and documenting the development of the disease process.

2.6. ECG Examination

2.6.1. TTE Inspection

The specific inspection methods are as follows:

The main equipment adopts GE company, VIVID7 color Doppler ultrasound diagnostic instrument, and M3S probe; frequency is 2.04.0 MHz

Operation methods and observation indicators

The patient was placed in left lateral decubitus position, and long-axis view of left ventricle in parasternal left ventricle was examined at bedside, and inner diameter of right ventricle (RV), inner diameter of left ventricle (LV), and anterior and posterior diameters of left atrium (LA) were measured. On apical four-chamber view, transverse diameter of right atrium (RA) was measured and tricuspid regurgitation was displayed by color Doppler. Simplified Bemoulli equation to estimate SPAP (unit: mmHg) (excluding pulmonary valve stenosis and outflow tract obstruction): P = 4 V2 + RAP, P is abbreviation of SPAP (systolic pulmonary artery pressure), V is systolic period measured by continuous Doppler peak tricuspid flow velocity (unit m/s), and right atrial pressure (RAP) was 10 mmHg

TTE showed direct signs of PTE: thrombus echo was observed in pulmonary artery or right heart. The thrombus is in the form of lump, grass, strip, etc.; echo can be high density, low density, mixed density, etc., or it can be attached to wall or free. Indirect signs: diagnostic criteria for acute right ventricular dysfunction in line with one or more of the following can be diagnosed:

Right ventricular dilatation:

Right ventricular end-diastolic diameter >30 mm (left ventricular long axis)

Right ventricular anteroposterior diameter/left ventricular anteroposterior diameter >0.6 during diastole (left ventricle, long axis)

Pulmonary hypertension:

Pulmonary artery systolic blood pressure> 30 mmHg

Tricuspid regurgitation rate> 2.8 m/s

The range of motion of anterior wall of right ventricle was decreased (<5 mm).

CT pulmonary angiography (CTPA) firstly performed a spiral CT scan of the entire lung, followed by contrast enhancement with nonionic contrast agent iopromide 370 (Uvixian), and three-dimensional angiography could be performed after scan

Definition of worsening or poor prognosis during hospitalization as (1) tracheal intubation, (2) cardiopulmonary resuscitation, (3) cardiogenic shock, and (4) death

2.7. Grouping and Analysis

According to the results of TTE examination, selected cases of normotensive pulmonary embolism were divided into right ventricular dysfunction and right ventricular function normal. The risk factors, clinical manifestations, laboratory tests, and prognosis were retrospectively analyzed.

3. Results

In direct signs of TTE, 1 case of right atrial thrombus, 1 case of right ventricular thrombus, and 5 cases of pulmonary artery thrombus were detected (the detection rate was 13%). Indirect signs of TTE, 25 of 53 normotensive APE patients were accompanied by RVD, accounting for 47% of normotensive pulmonary embolism. Pulmonary artery systolic blood pressure >30 mmHg in 23 cases (92%), right ventricular dilatation in 18 cases (72%), tricuspid regurgitation rate> 2.8 m/s in 16 cases (64%), hypokinesis of right ventricular anterior wall in 17 cases (68%), and left ventricle were changed in “D” shape in 7 cases (28%). Another 28 cases without RVD account for 53%. The high-risk factors, clinical manifestations, and other related clinical data of RVD and non-RVD are shown in Tables 1 and 2. There were no differences in age, gender, and risk factors (presence of deep vein thrombosis , previous history of lower extremity phlebitis or DVT/PE, cardiovascular and cerebrovascular diseases, smoking, malignancy, diabetes, immobilization). In patients with dyspnea, heart rate, jugular vein distention, and P2 hyperactivity were higher with RVD than those without RVD. There was no difference in chest tightness, chest pain, syncope, hemoptysis, palpitations, and systolic blood pressure at time of consultation.

Table 1

Risk factors of 53 normotensive patients with acute pulmonary embolism.

	Group with RVD (n = 25)	Without RVD (n = 28)
Age, years (x ±)	58±30	60±25
Male (cases (%))	15 (60)	16 (58)
Presence of DVT (cases (%))	10 (40)	11 (38)
Past history of lower extremity phlebitis or DVT/PE (cases (%))	5 (20)	5 (15)
Cardiovascular and cerebrovascular diseases (cases (%))	8 (27)	5 (15)
Smoking (cases (%))	10 (35)	9 (30)
Malignant tumor (cases (%))	2 (7)	3 (10)
Diabetes (cases (%))	5 (19)	5 (20)
Braking>48 h (cases (%))	3 (9)	4 (10)
Recent surgery (cases (%))	4 (2)	5 (15)
≤2 risk factors (cases (%))	19 (70)	20 (77)
≥3 risk factors (cases (%))	5 (25)	8 (30)

Table 2

General clinical data of 53 normotensive patients with pulmonary embolism.

	Group with RVD (n = 25)	Without RVD (n = 28)
Dyspnea (cases (%))	13 (47)	4 (13)∗
Chest pain (cases (%))	10 (35)	10 (36)
Chest tightness (cases (%))	18 (70)	15 (6)
Syncope (cases (%))	5 (15)	2 (5)
Hemoptysis (cases (%))	5 (18)	4 (14)
Palpitation (cases (%))	9 (33)	5 (20)
Cough, expectoration (cases (%))	10 (40)	15 (48)
Cyanosis (cases (%))	14 (50)	9 (30)
Jugular vein distension (cases (%))	15 (65)	4 (10) ∗∗
P2 hyperfunction (cases (%))	20 (70)	3 (6) ∗∗
Heart rate (at visit) (X¯±S)	105±16	90±15∗
Systolic blood pressure (at visit) (X¯±S)	130±30	130±20

TTE and PTE are known as combined echocardiography and pulmonary thromboembolism. TTE can directly observe whether there are thrombotic echoes in right atrium, right ventricle, main pulmonary artery, and left and right pulmonary artery bifurcations and dynamically display direction and activity of thrombus in real time and make a direct diagnosis of PTE. However, due to small proportion of central pulmonary embolism and limitation of bedside echocardiography due to limitation of image clarity and size of ultrasound window, probability of obtaining direct signs is very small. Only 5 patients were found in pulmonary artery (Figure 1): 1 case in right atrium (Figure 2) and 1 case found a thrombus in right ventricle. The detection rate is about 13%. Studies have suggested that 17–181 direct signs of thrombus found by TTE are markers of high early mortality. In this group, 5 cases (71%) of 7 cases of thrombosis detected by TEE died.

Figure 1

Short-axis section of great artery; sonographic image of thrombus at pulmonary artery bifurcation.

Figure 2

Apical four-chamber view, right atrium and right ventricle enlarged, sonographic image of right atrium thrombus.

39 cases with RVD before treatment blood gas analysis examination: arterial oxygen partial pressure, alveolar arterial oxygen partial pressure difference, and TTE examination: RVEDD, LVEDD, RVEDD/LVEDD, RA, LA, TR, SPAP, and no RVD compared. However, there was no difference in PCO2 and LA (see Table 3).

Table 3

Blood gas analysis and comparison of TTE indexes in 39 patients with normotensive pulmonary embolism ().

	With RVD n = 18	Without RVD n = 21
Blood gas analysis:
P a O 2(mmHg)	59.5 ± 16.31	74.5±19.5∗
(A − a)DO2(mmHg)	47.36±15.15	32.8±18.06∗
PCO 2(mmHg)	35.5±7.52	34.97±4.44
Echocardiogram:
RVEDD (mm)	29.88±5.94	20.97±2.25∗∗
LVEDD (mm)	37.55±5.55	42.65±3.06∗
RA (mm)	47.13±12.69	33.25±4.03∗∗
LA (mm)	31.16±7.88	33.06±4.44
V p (m/s)	3.76±0.87	2.39±0.55∗
RVEDD/LVEDD	0.85±0.24	0.46±0.09∗
SPAP (mmHg)	57.14±24.05	25.17±5.9∗

Clinical outcomes of normotensive APE patients (see Figure 3): 7 (28%) of 25 patients with RVD had PE-related worsening or poor prognosis (cardiopulmonary resuscitation, endotracheal intubation, cardiogenic shock) within 48 hours of diagnosis of PTE and death, 5 patients (20%) experienced PE-related death (sudden death), 2 patients improved after thrombolysis + anticoagulation therapy, 28 patients without RVD (0%) did not experience PE-related deterioration or death, 2 patients who experienced non-PE-related deaths occurred in 1 case (1 case died of coronary heart disease and heart failure during hospitalization, and 1 case died of multiple brain metastases from lung cancer and multiple cerebral infarction during follow-up 5 months later). The incidence of PE-related mortality and adverse prognostic events during hospitalization in RVD (20% and 28%, respectively) were different from those in non-RVD (0%) (Table 4).

Figure 3

Clinical results of 53 normotensive APE patients.

Table 4

Comparison of clinical results.

	Number of deaths, n (%)	Poor prognosis, n (%)
With RVD n = 25	5(20)	7(28)
Without RVD n = 28	0(0)	0(0)
P value	<0.05	<0.05

TTE examination showed that RVD was used as a predictor of death in APE patients, and its sensitivity, specificity, positive predictive value, and negative predictive value (see Table 5), following indicators, were calculated according to (Figure 3): PE-related death: sensitivity = 5/(5 ± 0) × 100% = 100%, specificity = 28/(28 ± 18 ± 2) × 100% = 58%, positive predictive value = 5/25 × 100% = 20%, negative predictive value = 28/28 × 100% = 100%; death from any cause: sensitivity = 5/(5 ± 2) × 100% = 71%, specificity = 26/(26 ± 2 ± 18) × 100% = 57%, positive predictive value = 5/25 × 100% = 20%, negative predictive value = 26/28 × 100% = 93%.

Table 5

TTE examination of RVD as a predictor of in-hospital mortality.

	PE-related death	Death from any cause
Sensitivity	100%	71%
Specificity	58%	57%
Positive predictive value	20%	20%
Negative predictive value	100%	93%

4. Discussion

Acute pulmonary embolism is a clinical and pathophysiological syndrome in which a variety of embolic substances block pulmonary artery and its left and right branches and cause pulmonary circulation dysfunction. In recent years, incidence of APE in my country has increased, and its mortality is second only to myocardial infarction and malignant tumor diseases in heart diseases [14]. It is necessary to take reasonable and timely treatment measures to help reduce mortality rate of patients. There are various types of emboli, including thrombus, tumor, water, fat, bacteria, air and other factors. The source of pulmonary embolism is mainly thrombus from right heart system or venous system. The most common case is that thrombus formed by deep vein of lower extremity falls off and then floats into pulmonary artery with blood flow. Therefore, it can be regarded as a continuous disease of venous thrombosis. Mohan et al. [15] found that almost 80% of patients with pulmonary embolism are accompanied by lower extremity deep vein thrombosis. Acute pulmonary embolism refers to patients with pulmonary embolism less than 14 days old. According to research statistics, acute pulmonary embolism is a disease with characteristics of “three highs.” “Three highs” refer to high disease incidence, high mortality, and high risk. According to statistics of experts, there are more than 200,000 patients with acute pulmonary embolism due to venous thromboembolism every year, and more than half of patients die due to embolism [16]. It was found that the number of patients with acute pulmonary embolism is more than 400,000 every year, and mortality rate is also very high. Autopsy-proven untreated acute pulmonary embolism has a mortality rate of approximately 25–30%. The number of new cases of pulmonary embolism in my country is increasing year by year, and disease has received more and more clinical attention.

The pathogenesis of acute pulmonary embolism is mainly that vascular endothelium of venous system is damaged, releasing coagulation factors, resulting in blood hypercoagulation. In Chaudhary et al. [17], three factors of Virchow are proposed to be caused by thrombosis of venous system. Risk factors for acute pulmonary embolism include primary and secondary. Lack of antithrombin, vascular endothelium easily damaged, hyperhomocysteininemia, and other factors are primary risk factors for acute pulmonary embolism [18]. It was found that if patients under the age of 40 have recurrent venous thromboembolism, and no pathogenic factors have been found or show genetic predisposition, and risk factors of disease have been found, genetic examination can be considered. Pulmonary embolism is easily induced by various pathophysiological changes, and these high-risk factors are secondary factors of acute pulmonary embolism. Advanced age, surgical history, pregnancy, trauma, fracture, long-term bed rest, malignant tumor, obesity, congestive heart failure, oral contraceptives, etc., are all common secondary factors. Risk factors for secondary pulmonary embolism coexist and interact with each other, affecting incidence. These factors can also exist as independent factors. Age is an independent risk factor. Falsetti et al. [19] found that with increase of age, incidence of pulmonary embolism gradually increased. Patients usually suffer from synergistic effect of multiple factors, resulting in thrombosis. Clinicians should attach great importance to these high-risk factors and try to avoid missed and misdiagnosed diseases.

TTE is noninvasive and safe and can accurately evaluate anatomical, functional, and hemodynamic changes of heart. During PE, a series of clinical and pathophysiological syndromes of pulmonary circulation disorder are caused by endogenous or exogenous emboli blocking main or branch of pulmonary artery, resulting in increased pulmonary artery pressure and increased right ventricular afterload. TTE can be manifested as right Atrium or right ventricle enlarges, tricuspid regurgitation flow increases, and velocity increases; PAD and RPAD widen; ventricular septum abnormal movement in short-axis view of left ventricle bulges toward left ventricle and makes left ventricle change in “D” shape, resulting in an increase in ratio of RV transverse diameter/LV transverse diameter: due to sharp increase in the right ventricular pressure and aggravation of myocardial hypoxia, the motion of the right ventricular wall generally decreased, while the apical motion of the right ventricular free wall was basically normal, showing segmental ventricular wall motion [20]. Abnormal movement is a more specific sign in acute PE. These abnormal findings are helpful in diagnosis of PE. This study mainly used phenomenon of increased pulmonary arterial pressure during PE, and after excluding common secondary pulmonary arterial hypertension, “unexplained” pulmonary arterial hypertension was used as standard for TTE suspected PE. Xie et al. [21] found that due to wide spectrum of pulmonary hypertension, some common secondary pulmonary hypertension diseases, such as congenital heart disease, heart failure, and chronic obstructive pulmonary disease, have been well known to clinicians. However, pulmonary hypertension caused by some rare diseases is often simply classified as “unexplained” pulmonary hypertension or primary pulmonary hypertension. Wang et al. [22] showed that in so-called “unexplained” pulmonary hypertension, PE and autoimmune diseases are two main causes. Therefore, it can be speculated that among “unexplained” pulmonary hypertension patients, there are a certain number of PE patients. We took this as suspected diagnosis standard, and a total of 20 patients with PE were suspected (accounting for 61% of total cases of suspected PE), and 11 cases of PE were further confirmed by pulmonary perfusion and spiral CT pulmonary angiography (accounting for 61% of total confirmed cases of PE); that is, diagnostic sensitivity is 61%. It can be seen that TTE provides more diagnostic clues than all other sources [23]. In patients with “unexplained” pulmonary hypertension, PE is the main cause, which has important practical significance in current low detection rate of PE in my country. Analysis of reasons: First, PE has long been considered a rare disease in my country, and clinicians have insufficient awareness of PE and poor diagnosis awareness, so there are fewer clinical suspicions of PE; second, there are relatively many chronic embolic pulmonary hypertension in my country. See, chronic PE is characterized by nonspecific clinical symptoms and persistent pulmonary hypertension. One of the advantages of TTE is that it can measure pulmonary arterial pressure noninvasively, and it is easier to detect patients with pulmonary arterial hypertension.