Educational mini-review: electrocardiographic indicators for pulmonary embolism

Introduction

Pulmonary embolism (PE) ranks as the third leading acute cardiovascular syndrome worldwide, trailing only behind myocardial infarction and stroke (1). Epidemiological research shows that the annual incidence rates of PE vary between 39 and 115 cases per 100,000 individuals (2). It also stands as the third leading cause of death from cardiovascular issues, following myocardial infarction and stroke (3). Notably, PE is the top preventable cause of mortality among hospitalized patients (4). The clinical manifestations of acute PE (APE) lack specificity. In most cases, suspicion of PE arises in patients experiencing symptoms such as dyspnea, chest pain, presyncope, syncope, or hemoptysis. Timely and accurate diagnosis, along with appropriate tailored treatments, can be lifesaving and reduce both short-term and long-term complications. There is a need for straightforward and rapid diagnostic methods to identify high-risk individuals, especially since immediate access to imaging techniques like computed tomography (CT) angiography or lung perfusion scintigraphy is not always feasible. However, the collection of electrocardiogram (ECG) parameters is noninvasive, relatively simple, and cost-effective, making it a widely utilized and valuable tool for assessing PE. Serial ECGs can reveal diagnostic indicators of embolism. As early diagnosis of PE holds significant importance, it is crucial for physicians to have a deep understanding of its ECG characteristics. Based on our prior studies and utilizing the electrocardiology data obtained from patients with PE at our electrocardiography center. We extended the analysis from conventional ECG phenotypes associated with PE to encompass rarer ECG manifestations. Furthermore, we evaluated the prognostic utility of these ECG phenotypes in determining the severity of PE.

The electrocardiographic observations in cases of APE have been a topic of frequent discussion ever since their initial documentation by McGinn and White in 1935 (5). They noted that the S1Q3T3 pattern is typically seen in ECGs for PE. In our clinical observations, the majority of PE patients exhibit this ECG characteristic. For example, a CT pulmonary angiography (CTPA) of a 19-year-old male showed PE. The ECG indicated an S wave in lead I, a qR pattern with T wave inversion in lead III (Figure 1A). Subsequent findings typically encompass the following: sinus tachycardia and various atrial arrhythmias, conduction abnormalities predominantly involving right bundle branch block (RBBB), shifts in the QRS axis, including the SIQIII pattern and occasional Q waves in aVF, ST-segment displacement, T-wave inversion (TWI) in lead III and the right precordial leads, and alterations in the configuration of the P wave. It’s worth noting that bronchoconstriction resulting from serotonin release after embolic impact may contribute to changes in the P wave (6). Additionally, acute right ventricular (RV) dilation can lead to deviations in the QRS axis (6).

Figure 1 The ECG pattern and brief introduction of patients with pulmonary embolism. (A) A 19-year-old male had a pulmonary CTA that showed multiple pulmonary embolisms located at the bifurcations and in several branches of the main pulmonary arteries on both sides. The ECG indicated a sinus rhythm with a heart rate of 94 bpm. It showed an S wave in lead I, a qR pattern with T wave inversion in lead III, and T wave inversion in V1. (B) A 38-year-old male underwent pulmonary angiography which revealed pulmonary embolism in the main pulmonary artery, as well as in the right and left pulmonary arteries. The ECG indicated atrial flutter with a heart rate of 132 bpm and a complete right bundle branch block. (C) A 26-year-old male underwent a CTPA that revealed pulmonary embolisms in the inferior pulmonary arteries on both sides. The ECG showed sinus tachycardia with a heart rate of 116 bpm and a complete right bundle branch block. (D) A 42-year-old female had a CTPA which showed pulmonary embolisms in the pulmonary arteries of the right inferior lobe and the left lingula. The ECG indicated a sinus rhythm with a heart rate of 77 bpm, T wave inversions in leads III, V1 to V3, and low voltage in the limb leads. (E) A CTPA performed on a 14-year-old patient revealed multiple pulmonary embolisms in the branches of the pulmonary arteries bilaterally. The ECG displayed sinus tachycardia with a heart rate of 118 bpm, an S wave in lead I, T wave inversion in lead III, and T wave inversion from V1 to V4, showing decreasing amplitude. (F) A 60-year-old female underwent a CTPA which revealed multiple pulmonary embolisms at the bifurcations and in various branches of the main pulmonary arteries on both sides. The ECG indicated a sinus rhythm at 84 bpm, T wave inversion from V1 to V3 with decreasing amplitude, and an ST-segment strain pattern. (G) A 60-year-old male experienced syncope for 1 day. A CT pulmonary angiography indicated multiple pulmonary embolisms in the branches of the pulmonary arteries on both sides. The ECG showed a sinus rhythm at 62 bpm, a Qr pattern, and T wave inversion in lead III. It also indicated a heart rate-corrected QT interval prolonged to 516 ms, with T wave inversion present in leads II, III, aVF, and V1–V3. (H) A 69-year-old male underwent a CTPA that showed multiple pulmonary embolisms in the branches of the pulmonary arteries on both sides. The ECG revealed a sinus rhythm with a heart rate of 94 bpm, T wave inversion in leads III and V1, and a Brugada phenocopy. (I) A 72-year-old male underwent a CTPA which revealed pulmonary embolisms in the main branch of the right middle lobe pulmonary artery and its adjacent branches. Additionally, the ECG indicated sinus tachycardia with a heart rate of 121 bpm, a Qr pattern in leads V1 and aVR, and an S wave in lead I. (J) A 60-year-old male underwent a CTPA that revealed multiple pulmonary embolisms in both the left and right pulmonary arteries. The ECG displayed sinus tachycardia with a heart rate of 112 bpm, the S1Q3T3 pattern, a QR pattern in V1, an ST-segment strain pattern, and T wave inversion from V1 to V4 with decreasing amplitude (as denoted by the arrow). CT, computed tomography; CTA, computed tomography angiography; CTPA, computed tomography pulmonary angiography; ECG, electrocardiogram.

PE places an additional load on the right ventricle, leading to heightened pressure within the pulmonary artery, right atrium, and right ventricle. These can result in the enlargement of the right atrium and ventricle, presenting as a RV strain issue characterized by indicators such as the S1Q3T3 sign, TWI in V1 to V4, and the development of new RBBB. The expansion of the right ventricle causes a clockwise repositioning of the heart, and ischemic TWI in the right ventricle can be observed in leads V1 to V5 (7). Petrov’s research indicates that the emergence of the RBBB on an ECG in patients with PE could be a key indicator of significant blockage in the main pulmonary artery. Instances of RBBB were not observed in patients with embolisms located in peripheral regions (8). The presence of RBBB on an ECG is a marker of sudden increased pressure on the right side of the heart. The hypothesis is that in patients with PE the RBBB may be attributed to a decrease in blood flow to the tiny vessels within the right bundle branch. This phenomenon is believed to result from the swift expansion of the heart’s right ventricle (9). In our electrocardiography center, a 38-year-old male underwent pulmonary angiography which revealed PE in the main pulmonary artery, as well as in the right and left pulmonary arteries. The ECG indicated atrial flutter and a complete RBBB (CRBBB) (Figure 1B). However, the appearance of CRBBB may also be observed in many other places. For instance, we observed a 26-year-old male who underwent a CTPA, which revealed PEs in the inferior pulmonary arteries on both sides. The ECG showed sinus tachycardia and a CRBBB (Figure 1C).

The ECG signs of APE encompass irregularities in heart rhythm and alterations in P waves, QRS complexes, or T waves. These changes are known to vary significantly and often appear temporarily. In 1970, Romhilt et al. found that the transient development of abnormal Q waves with TWI in the precordial leads V2 through V5 (10). Patients with APE often exhibit negative T waves in the precordial leads of their ECGs. However, negative T waves can also occur in cases of acute coronary syndrome (ACS) and Takotsubo cardiomyopathy (TC). The patterns of negative T waves vary among APE, ACS, and TC, aiding in distinguishing between these conditions. Specifically, the presence of negative T waves in both leads III and V1 accurately identifies APE with a sensitivity of 90% and a specificity of 97%. In our observations, we noted that the ECGs of patients with PE often display specific characteristics. For instance, a 42-year-old female underwent a CTPA that confirmed PE, and her ECG showed T wave inversions in leads III and V1–V3 (Figure 1D). Further observations revealed that ECGs of PE patients often show T wave inversions in the precordial leads, characterized by a gradual decline (Figure 1E,1F). Conversely, negative T waves in lead-aVR coupled with their absence in leads V1 indicate TC with a sensitivity of 95% and a specificity of 97%. Lead III is oriented towards the lower part of the right ventricle, while leads V1 and V2 target the front of the right ventricle. Generally, patients with ACS due to left anterior descending (LAD) artery disease predominantly showed negative T waves in the V2 to V4 leads of the precordial area, which corresponds to the front part of the left ventricle (11).

In a previous report, we presented a case involving a patient with PE whose ECG revealed prolonged QT-interval and simultaneous TWI in both inferior and anterior leads (Figure 1G). It is important to distinguish these ECG alterations from conditions such as long QT syndrome, myocardial ischemia, TC, post-pacing T-wave memory, hypertrophic cardiomyopathy, and subarachnoid hemorrhage (12). Similarly, Lui observed generalized TWI along with prolonged QT intervals in patients with APE, suggesting that these cardiac changes might be influenced by catecholamines or arise from histamine-induced myocardial ischemia (13). APE can sometimes lead to temporary prolongation of the QT interval accompanied by pronounced TWI, placing it among the potential secondary causes of long QT syndrome (7,14,15). The ECG alterations observed in acute pulmonary thromboembolism (APTE) are likely triggered by sudden overload on the right ventricle. However, factors such as myocardial ischemia, impaired blood flow to the heart’s electrical system, low oxygen levels, and the impact of various biochemical agents like catecholamines and histamines might also contribute to these ECG changes (13). Nonetheless, the precise electrophysiological underpinnings of these observations in individuals with APE remain elusive and are subjects for future research.

Zhai and He have recently described a case of an elderly man with massive PE who exhibited a Brugada electrocardiographic pattern (16). At our electrocardiography center, we have also observed this type of ECG in patients with PE. For example, A 69-year-old male underwent a CTPA that showed multiple PEs in the branches of the pulmonary arteries on both sides. The ECG revealed a sinus rhythm with a heart rate of 94 bpm, T wave inversion in leads III and V1, and a Brugada phenocopy (BrP) (Figure 1H). The term BrP refers to rare instances where the ECG pattern mirrors that of Brugada syndrome, yet is triggered by diverse clinical scenarios. The causes of BrP are divided into six categories: metabolic disturbances, mechanical compression, PE, myocardial ischemia, heart and pericardial conditions, ECG alterations, and other miscellaneous factors (17). In cases of massive APE leading to increased pulmonary vascular resistance, a rapid surge in RV preload could intensify existing conditions of high RV stress, potentially causing RV myocardial ischemia across the wall. This ischemic activity in the right ventricle may be the reason behind the ST-segment elevation observed as type 1 or type 2 Brugada patterns during cardiac ischemic episodes (16).

Lead V1 is positioned close to the outflow tract of the right ventricle. The configuration of the QRS complex in V1 can be influenced by shifts in the ventricular septum’s position as well as by alterations in the ventricles’ volume and pressure (18).

A QR pattern in lead V1 is highly indicative of PE, as increased afterload can lead to RV hypertrophy, ischemia, dilation, and/or failure (19).

At our electrocardiography center, we also identified this rare ECG pattern in patients with PE (Figure 1I,1J). Ischemia in the right ventricle can account for the elevation of the ST segment observed in V1. The QR sign and ST elevation in lead V1 can occur in conditions such as acute anteroseptal myocardial infarction, PE, and cardiac amyloidosis. While the QR sign and ST elevation in V1 are specific ECG markers for PE, they can also appear in cases of cardiac amyloidosis due to widespread infiltration or fibrosis of the heart muscle. This pattern, resembling a false heart attack in the precordial leads, should be distinguished from an actual anteroseptal myocardial infarction and cardiac amyloidosis (20). In summary, the ECG characteristics are consolidated in Table 1.

The Geneva and Wells criteria are frequently referenced as clinical PE probability scores. Both of these scoring systems incorporate heart rate among their indicators (21).

Pertinent prognostic outcome

APE has the potential to quickly result in hemodynamic failure and death. Contemporary guidelines advocate for the risk stratification of patients. This is because those identified as high-risk for clinical decline or death may be eligible for more aggressive interventions in addition to anticoagulation, including options like thrombolysis or surgical thrombectomy. On the other hand, patients assessed as low-risk may often be managed with outpatient treatment.

In 2001, Daniel and colleagues created an ECG scoring system to evaluate the severity of pulmonary hypertension in individuals with PE. This system considers factors such as tachycardia, RBBB, TWI, and the S1Q3T3 pattern. The scoring spans from 0 to 21, where higher scores denote more adverse clinical results (22).

Following the introduction of the Daniel score, numerous studies have explored the role of ECG in forecasting outcomes for PE. These investigations have broadened the application of ECG, incorporating indicators not covered by the Daniel score. These additional findings include ST-segment depression, ST-segment elevation, a Qr pattern in lead V1, right axis deviation (RAD), and P pulmonale, among others.

In 2017, Qaddoura et al. conducted a meta-analysis to assess the effectiveness of electrocardiography in predicting clinical worsening and mortality in cases of APE. This comprehensive review analyzed 39 studies, encompassing 9,198 patients, and found that certain ECG characteristics could forecast adverse outcomes in APE patients. These outcomes include clinical decline, mortality during hospitalization, and mortality within 30 days. The specific ECG features most indicative of in-hospital mortality include the S1Q3T3 pattern, CRBBB, TWI, ST-segment depression in leads V4 to V6, ST-segment elevation in V1 (STE-V1) and in lead III (STE-III), Qr pattern in V1, RAD, atrial fibrillation, and patterns suggesting RV transmural ischemia (23).

Limitation

While the extended analysis of conventional and rare ECG phenotypes enhances our understanding of PE, it faces limitations. The predictive accuracy of ECG phenotypes can vary, particularly with rarer manifestations that may not be well-represented in smaller sample sizes. Additionally, the correlation between specific ECG changes and the clinical severity of PE is not universally consistent, potentially leading to diagnostic uncertainty. These factors may affect the reliability of ECG as a standalone tool for assessing PE severity, underscoring the need for complementary diagnostic approaches.

Conclusions

Following the introduction of the Daniel score, numerous studies have explored the role of ECG in forecasting outcomes for PE. These investigations have broadened the application of ECG, incorporating indicators not covered by the Daniel score. These additional findings include ST-segment depression, ST-segment elevation, a Qr pattern in lead V1, RAD, and P pulmonale, among others.

Medical professionals should understand the specific ECG signs indicative of PE, which causes RV stress and leads to distinctive electrocardiographic changes on a 12-lead ECG. Observations such as the S1Q3T3 complex, negative T-waves in precordial leads with a clockwise rotation, the pulmonary P-wave, RBBB, or unusual axis deviations signal the presence of PE. Additionally, it is crucial to identify other notable ECG patterns associated with PE, including prolonged QT-interval, concurrent TWI in both inferior and anterior leads, a Brugada ECG pattern, and the QR pattern and ST-elevation in lead V1.

APE represents a significant medical challenge, linked to considerable illness and death. For those suspected of having APE, certain indicators can assist in quickly pinpointing patients with PE and identifying those at high risk who might gain from thrombolytic treatments or mechanical interventions. The ECG stands as a critical resource for forecasting outcomes in PE cases, particularly in settings where advanced technologies are unavailable. There is a pressing need to create a novel ECG scoring system to help healthcare providers detect and categorize the risk levels of patients with PE. Simultaneously, we should recognize the importance of considering a wide range of etiologies in clinical practice, emphasizing that clinical context and suspicion are critical in diagnostics. ECG, while significant, should not solely determine the diagnosis but rather complement a broader diagnostic strategy. This integrative approach leads to a more accurate and comprehensive understanding of the patient’s condition, improving diagnostic and treatment outcomes.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-54/prf

Funding: This study was supported in part by Anhui Provincial Health Research Project (No. AHWJ2022a008). The funders had no role in the study design, data collection and analysis, decision to publish, nor preparation of the manuscript.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-54/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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