Electrocardiographic manifestations: pulmonary embolism

The Journal of Emergency Medicine, Vol. 21, No. 3, pp. 263–270, 2001 Copyright © 2001 Elsevier Science Inc. Printed in the USA. All rights reserved 0736-4679/01 $–see front matter

PII S0736-4679(01)00389-4

Selected Topics: Cardiology Commentary

ELECTROCARDIOGRAPHIC MANIFESTATIONS: PULMONARY EMBOLISM Theodore C. Chan,

MD,*

Gary M. Vilke,

MD,*

Marc Pollack,

MD,†

and William J. Brady,

MD‡

*Department of Emergency Medicine, University of California San Diego Medical Center, San Diego, California, USA; †Department of Emergency Medicine, York Hospital, York, Pennsylvania, USA; and ‡Department of Emergency Medicine, University of Virginia Health System, Charlottesville, Virginia, USA Reprint Address: Theodore C. Chan, MD, Department of Emergency Medicine, UCSD Medical Center, 200 West Arbor Drive #8676, San Diego, CA 92103-8676

e Abstract—The electrocardiographic findings associated with pulmonary embolism have been well described in the medical literature for over 50 years. These abnormalities include changes in rhythm, QRS axis, and morphology, particularly in the QRS and T waves. Such findings may reflect hemodynamic changes, such as right heart strain, as well as myocardial ischemia associated with the disease. Although certain findings may correlate with the severity of pulmonary embolism, the overall utility of the electrocardiogram is limited due to the variable presence, frequency, and transient nature of most of the abnormalities associated with the disease. © 2001 Elsevier Science Inc.

CASE PRESENTATIONS Case 1 A 67-year-old woman was brought to the Emergency Department (ED) by ambulance after two syncopal episodes earlier in the morning. On arrival, the patient noted some chest pain “not like my usual angina,” but denied shortness of breath, headache, abdominal pain, or lightheadedness. Past history was notable for angina, diabetes, and hypertension. Physical examination revealed an elderly woman with labored breathing, tachypneic at a rate of 40 breaths/min, hypotensive with blood pressure of 71/35 torr, and pulse rate of 76 beats/min. The chest examination revealed clear breath sounds bilaterally, with regular rate and rhythm on cardiac examination. The abdomen was soft and nontender with no pulsatile masses. There was mild bilateral pitting edema in the lower extremities. In the ED, oxygen saturation was 100% on oxygen by face mask. A 12-lead EKG was obtained (Figure 1), revealing a sinus rhythm at 95 with an occasional premature ventricular contraction, superior right axis deviation (RAD), and low QRS voltage over the precordium. The patient was resuscitated with i.v. fluids and started on dopamine. A bedside abdominal ultrasound revealed no free fluid in the abdomen or pelvis and a normal aorta. The patient was subsequently admitted by the cardiology service to the Coronary Care Unit (CCU). The patient had a difficult hospital course with persistent hypotension. She developed hypoxia and was intubated for respiratory compromise. The patient deteriorated and died approximately 2 days after admission. On autopsy, a large pulmonary embolus was found in the

e Keywords—pulmonary embolism; electrocardiographic findings; review

INTRODUCTION Over 650,000 cases of pulmonary embolism (PE) are diagnosed in the United States annually. Mortality rates have been reported as high as 10%, and little improvement in survival has occurred since the 1960s. Despite new diagnostic methods and technology, many cases are not discovered until autopsy (1–3). Since the 1930s, a multitude of abnormalities on 12-lead electrocardiogram (EKG) have been described in patients with acute PE. These EKG findings are often variable with poor sensitivity and specificity for the disease, leading many to conclude that the 12-lead EKG is of little value in this setting. However, recent work has focused on the use of the EKG in assessing severity, duration, and prognosis for acute PE. We review the findings on 12-lead EKG associated with acute PE and their potential significance. 263

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Figure 1. 12-lead EKG revealing occasional premature ventricular contractions, superior RAD, and low QRS voltage across the precordium in a patient subsequently diagnosed with pulmonary embolism on autopsy.

right main bronchus and was determined to be the cause of death.

Case 2 A 64-year-old woman complaining of 10 h of shortness of breath was brought to the ED by paramedics. She had been recently discharged after hospitalization for lower leg cellulitis. Paramedics found the patient with labored respirations and an oxygen saturation of 80% on room air. Oxygen was administered by face mask in the field. On arrival in the ED, the patient’s vital signs were temperature of 38.2°C (100.8°F), respiratory rate of 24 breaths/min, blood pressure of 81/61 torr, and pulse rate of 120 beats/min. On examination, the patient was an elderly woman in moderate respiratory distress. Chest auscultation revealed shallow respirations with a tachycardia. The abdomen was obese, but nontender, and there was 1⫹ pitting edema in the extremities bilaterally. Oxygen saturation was 94% on non-rebreather mask at 15 L/min oxygen. A 12-lead EKG was obtained (Figure 2), revealing a sinus tachycardia with incomplete right bundle branch block (RBBB), a new finding when compared to a pre-

vious EKG. Given the acuity of presentation and evidence of respiratory compromise, concern was raised for possible PE. The patient had a computed tomography (CT) scan of the chest, which revealed a large saddle embolus at the bifurcation of the left main pulmonary artery (PA). As the patient was being prepared for fibrinolytic therapy, she rapidly deteriorated into acute respiratory failure and subsequently suffered an asystolic cardiac arrest. The patient was intubated, and advanced cardiac life support measures were instituted. Despite these efforts, the patient could not be resuscitated.

Case 3 A 42-year-old man presented to the ED with acute onset shortness of breath and chest pain. The patient had undergone knee surgery 1 week prior to presentation. On examination, the patient’s heart rate was 80 beats/min, blood pressure was 112/72 torr, and respiratory rate was 28 breaths/min. Oxygen saturation on room air was 94%. The chest examination revealed tachypnea, but otherwise clear lung fields. The extremities were notable for a

EKG Manifestations: Pulmonary Embolism

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Figure 2. 12-lead EKG revealing sinus tachycardia and a new incomplete RBBB in a patient diagnosed with PE on chest CT scan.

Figure 3. 12-lead EKG revealing a new RBBB in a patient diagnosed with PE on ventilation/perfusion scanning.

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Figure 4. 12-lead EKG revealing the “classic” S1Q3T3 pattern. This patient had a normal pulmonary angiogram with no evidence of PE.

recent right knee surgical scar with surrounding edema, as well as swelling of the right calf, ankle, and foot. A 12-lead EKG was obtained (Figure 3), revealing a new RBBB pattern compared to the pre-operative EKG obtained earlier. Given the history of recent knee surgery and the acute shortness of breath, a ventilation/perfusion scan was obtained and revealed an unmatched perfusion defect in the right lung field. The scan was interpreted as high probability for PE. The patient was admitted for treatment with anticoagulation therapy and had an uneventful hospital course.

Case 4 A 58-year-old woman was brought to the ED by ambulance after suffering a witnessed syncopal event while eating dinner. Paramedics found the patient awake and alert with stable vital signs in the field. On arrival in the ED, the patient complained of lightheadedness, but denied shortness of breath and chest pain. On examination, the patient’s vital signs were: pulse rate 92 beats/min, blood pressure 136/82 torr, and respiratory rate 16 breaths/min. Chest, cardiac, and abdominal examinations were normal. There was mild bilateral calf tenderness, but no edema. A 12-lead EKG was obtained (Figure 4), revealing

sinus rhythm and an S1-Q3-T3 pattern. Because of the concern for PE, the patient underwent a pulmonary angiogram, which was normal. The patient was admitted for further observation and evaluation of her syncope. Her hospital course was uneventful with no etiology determined for her syncopal episode, and she was subsequently discharged with no plan for further treatment.

DISCUSSION Despite new technologic advances, the diagnosis of acute PE remains difficult for the Emergency Physician (EP). In fact, anywhere from 10 to 30% of cases of acute massive PE are not diagnosed until discovered on autopsy (1). A number of specific EKG findings have been described in association with acute PE. Some investigators have attempted to develop diagnostic prediction rules based on EKG findings (4). Because these findings are quite variable, such efforts have met with limited success. Recent work has focused on the ability of the EKG to reflect the severity, duration, and prognosis for patients with acute PE. McGinn and White first reported in 1935 the classic “S1Q3T3” pattern finding (described as a prominent S wave in lead I, ST segment ascent in lead II, and Q wave with inverted T wave in lead III) in seven patients with

EKG Manifestations: Pulmonary Embolism

acute cor pulmonale secondary to PE (5). Subsequently, Barnes reported the association of RAD in 1937, and Durant et al. reported the finding of transient RBBB in 1939 in acute PE patients (6,7). Other findings reported during this time period include atrial dysrhythmias, ppulmonale, and T wave inversions (8,9). Interestingly, in 1940, Sokolov et al. reviewed 50 PE patients and found most had either a normal EKG or nonspecific findings (10).

Pathophysiology The mechanism by which acute PE causes EKG changes remains unclear. These changes have been attributed to ischemic, hemodynamic, anatomic, metabolic, and autonomic changes that affect the electrical pathways of cardiac tissue (11). Hemodynamically, an acute PE causes mechanical PA flow obstruction, resulting in elevated PA and right heart pressures, as well as right atrial and ventricular dilatation. These changes can result in EKG changes consistent with right heart strain and atrial enlargement patterns. In addition, increase in right ventricular wall tension can lead to ischemia in these tissues causing ST and T wave changes. In cases of massive PE, significant drops in right ventricular output can decrease left ventricular preload, resulting in hypotension and decreased myocardial perfusion globally. Nevertheless, the EKG abnormalities associated with PE cannot be completely attributed to hemodynamic and ischemic changes. There is often a time lag between the EKG abnormalities and the development of pulmonary hypertension and right ventricular strain and dilatation. In addition, EKG changes often persist well after PA pressures and ventricular size have returned to normal. Sreeram et al. reported that EKG abnormalities found in PE patients do not correlate with the hemodynamic status of the heart seen on echocardiography (4). Ferrari et al. reported that in those PE patients with ischemic changes on EKG, there was no evidence of myocardial perfusion abnormality on scintigraphic scanning (12). Others have suggested that EKG abnormalities may be attributable to a catecholamine-mediated phenomena or possibly induced by histamine release, resulting in ischemia at the cellular level (13,14).

EKG Findings Over the last 50 years, there have been a multiplicity of studies describing a wide range of specific EKG abnormalities associated with PE (Table 1; 4,14 –23; Lewis

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KD, Pollack ML, Schlenker MK, unpublished data). The large majority of these studies are specific to patients with no preexisting cardiac or pulmonary disease. Normal EKG. A completely normal EKG has been reported in anywhere from 9 to 26% of patients with acute PE (1,3). Sreeram et al. reported an incidence of normal EKG in one quarter of acute PE patients on admission. Moreover, the majority of these patients (18% of the total) had EKGs that remained normal throughout their hospitalization (4). Rhythm Disturbances. Abnormal rhythm disturbances, including sinus tachycardia, first degree atrio-ventricular block, premature atrial and ventricular beats, atrial fibrillation, and flutter have been reported in association with acute PE at varying rates. Atrial fibrillation and flutter were reported to occur in as many as 18% and 35%, respectively, of acute PE patients by Weber et al. and Sreeram et al., and as few as 0 to 3% in other studies (4,16 –19). Right Bundle Branch Block. Complete or incomplete RBBB has been described as a “typical,” but variable finding with an incidence ranging from 6% to as high as 67%. In addition, RBBB can be associated with ST segment elevation and upright T waves in lead V1, potentially mimicking antero-septal or posterior infarct patterns (4). Right bundle branch block in the setting of acute PE is often transient and has been reported to resolve in most cases within 14 to 41 weeks of onset (19,24). Axis Changes. Right, left, and indeterminate QRS axis changes have been reported with variable frequency in acute PE patients. Whereas RAD is described as the classic axis change associated with PE, some investigators have reported left axis deviation (LAD) as occurring with greater frequency (4,5,19,25). Part of the variability may relate to the different parameters defining RAD, LAD, and indeterminate deviations. Indeterminate axis have been defined as axis ranging from 180°-90°, a range that also has been described as extreme or superior RAD. In addition, preexisting disease may impact the incidence of axis deviations. In the Urokinase in Pulmonary Embolism Trial, Stein et al. reported that LAD occurs more frequently than RAD in the PE study population; however, when those with preexisting cardiopulmonary disease are excluded, the incidence of LAD and RAD are equivalent (19). Transition Zone Shift. Clockwise rotation and shift of the transition zone (the precordial lead site where R and

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Table 1. Reported EKG Abnormalities and Their Frequencies in Patients with Pulmonary Embolism Cutforth 15

Weber 16

Szucs 17

Sasahara 18

Stein 19

Petruzzelli 20, 22

Stein 22

Sreeram 4

Ferrari 14

Rodgers 23

Lewis, Pollack

Year published n of PE patients

1958

1966

1971

1973

1975

1986/1995

1991

1994

1997

2000

unpublished

50

26

50

132

90

89

49

80

49

35

Normal Rhythm Disturbances Sinus Tachycardia PAC or PVC Afib or flutter 1 AVB

24%

13%

13%

30%

26%

9%

26%

4% 3%

12% 3% 5%

42% 9% 4%

53%

23% 35% 12%

69% 6% 0% 1%

44%

4% 3% 2%

RBBB Low Volt QRS Transition Zone Shift

14%

23%

8%

15% 16%

13% 3%

29%

4%

7%

17%

7% 7%

3% 14%

Axis Deviation RAD LAD Indeterminate S1Q3T3 ST or T abnormalities ST depression/ elevation S in I, L Q in III, F T inversion in III, F in V1, V2 P pulmonale

66%

19%

15%

17%

5% 12%

28%

23%

11%

46%

77%

64%

12%

41% 31%

4%

8% 5%

4% 18%

2% ⱕ6%

ⱕ6%

67% 20% 51%

14%

33% 2% 31%

9%

16%

50%

6%

S wave amplitudes are equivalent) to lead V5 has also been reported with variable frequency in PE patients. Sreeram reported an incidence of as many as 51% of PE patients with evidence of transition zone shift to V5 (4). Morphologic Changes. Along with sinus tachycardia, the most common EKG abnormalities associated with acute PE patients are morphologic, particularly alterations in the ST segment and T wave. P Wave. Increase in the P wave amplitude greater than 2.5 mV in lead II (p-pulmonale) has classically been attributed to right atrial hypertrophy or enlargement associated with acute PE (4). P-pulmonale has been reported in anywhere from 2 to 31% of PE patients (16,23). In addition, Petruzzelli and Manganelli reported PR depression and displacement in nearly one-third of PE patients studied (20,21). QRS Wave. Low voltage (less than 5 mV in all limb leads) in the QRS wave in all limb leads has been reported in up to 29% of PE patients (14). Other QRS

12%

28%

68%

50% 10% 17% 23% 6%

19%

9%

49% 42%

12%

145

73% 49%

14% 28% 14%

33% 27% 8%

35% 44% 2%

50% ⱕ6%

68% 5%

wave findings reported with acute PE include a late R wave in avR and slurred S in V1 or V2 (23). ST segment and T wave. Alterations in the ST segment and T wave are the most frequent changes seen on EKG in PE patients (3,4,19). Nonspecific ST depression or elevation has been reported in up to half of all PE patients (20,21). T wave inversions diffusely and in the inferior or anterior leads also have been frequently reported (4,19,23,24). S1Q3T3. The finding of a large S wave in lead I, Q wave and inverted T wave in lead III has often been mistaken as pathognomonic for acute PE after being first described in the 1930s (3,5). The reported incidence of the S1Q3T3 combination has varied from 10% to as high as 50% of acute PE patients (10,14). Sreeram reported separate frequencies for an S wave greater than 1.5 mV in leads I and L (73%), Q wave in III and F (49%), and T wave inversion in III and F (33%) in a study of 80 patients with confirmed PE (4). Stein reported that, similar to RBBB,

EKG Manifestations: Pulmonary Embolism

S1Q3T3 is frequently transient, resolving within 14 days after onset of the disease (19).

Utility of the 12-lead EKG Findings on the 12-lead EKG have been studied to assess for potential utility in the diagnosis of acute PE and in determining the severity and prognosis of the disease. Sreeram et al. studied 49 patients with confirmed PE by using blinded reviewers to assess admission and hospital stay EKGs for evidence of right ventricular overload. A PE was considered probable in 76% of the admission EKGs if three or more of the following were found: RBBB (with associated ST segment elevation or T wave inversion in V1); prominent S waves in I and avL; transition zone shift to V5; Q waves in III and avF; RAD or indeterminate axis; low QRS voltage in the limb leads; and T wave inversions in III, avF, or V1– 4 (4). In addition, reviewers read 170 EKGs from patients with diagnoses other than acute PE. Using the same guide, Sreeram reported there was only one false-positive reading for acute PE among these EKGs. However, Sreeram’s rule performed poorly among those with lung disease. Reviewers found eight false-positive EKGs among an additional 10 EKGs obtained from patients with a history of chronic obstructive pulmonary disease in whom the diagnosis of PE was excluded (4). Petruzzeli studied 21 EKG abnormalities in 245 patients with suspected PE (of whom 145 had the diagnosis confirmed). PR displacement, late R in avR (late R wave amplitude of 1.5 mm or more, see aVR in Figure 4), slurred S in V1 or V2 (V2 in Figure 2), the S1Q3T3 pattern, and T wave inversion in V1 or V2 (but not diffuse T wave inversions) were significantly more common in patients with confirmed PE (20,21). Alternatively, Nazeyrolas et al. studied 70 patients admitted for suspected PE and found only an S wave in I and Q wave in III significantly more common among those with confirmed PE (26). Rodgers et al. studied the EKGs of 246 patients with suspected PE (of whom 49 were confirmed and 163 excluded diagnostically), comparing the frequency of 28 different electrocardiographic findings supposedly associated with the diagnosis. Of these, the investigators found only sinus tachycardia (42.2% vs. 22.5%, respectively) and incomplete RBBB (6.7% vs. 0%, respectively) significantly more common in confirmed PE patients than in those excluded. In this study population, Sreeram’s guide of three or more findings on EKG had only a 26.7% sensitivity and 57.1% positive predictive value for PE. Moreover, the S1Q3T3 pattern was equally prevalent among those with and without PE (11.6% vs. 13.5%, respectively; 23).

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Investigators have also studied the association of EKG abnormalities with severity of disease and prognosis. Patients with ST depression and T wave inversion in leads V1 and V2 have been shown to have an increased number of unperfused lung segments on scintigraphy (20,21). Yoshinaga et al. reported that the timing of peak T wave inversions in the precordial leads correlated with changes in hemodynamic status following fibrinolytic therapy in 15 patients with PE (13). Alternatively, Sreeram et al. reported no association between the number of abnormalities seen on EKG and right ventricular overload, size, or pressures (4). Ferrari et al. studied 80 confirmed PE patients, of whom 59 were diagnosed with massive PE. An “anterior ischemic pattern,” as indicated by T wave inversions in the precordial leads, was more common in massive PE patients (85% vs. 19%, respectively) and more often occurred earlier in the disease course (within 24 h of onset). Moreover, Ferrari found that early resolution of these T wave inversions correlated with improvements in hemodynamic status and overall prognosis (14). Despite these reports, the use of the 12-lead EKG in terms of diagnosis, severity, and prognosis determination remains limited. There are no EKG findings unequivocally diagnostic of PE. However, the greatest utility of the EKG in this setting remains its ability to evaluate for other potential life-threatening diagnoses in the differential, including myocardial ischemia, infarction, and acute pericarditis.

CONCLUSION A wide range of EKG abnormalities, including patterns associated with right heart strain, have been described in patients with PE. These changes may relate to hemodynamic, ischemic, and other myocardial changes associated with the disease. In addition, EKG findings may correlate with both severity and prognosis for PE. Although EKG abnormalities may raise suspicion for PE, the overall utility of these findings remains limited because of their variable frequency, presence, and transient nature. There are no EKG findings unequivocally diagnostic of PE. The greatest utility of the EKG in this setting is to evaluate for cardiac etiologies for the patient’s presentation, such as myocardial ischemia and infarction.

REFERENCES 1. Panos RJ, Barish RA, Whye DW, Groleau G. The electrocardiographic manifestations of pulmonary embolism. J Emerg Med 1988;6:301–7.

270 2. Palla A, Petruzzelli S, Donnamaria V, Giuntini S. The role of suspicion in the diagnosis of pulmonary embolism. Chest 1995; 107:21S–24S. 3. Hubloue I, Schoors D, Diltoer M, Van tussenbroek F, DeWilde DE. Early electrocardiographic signs in acute massive pulmonary embolism. Europ J Emerg Med 1996;3:199 –204. 4. Sreeram N, Cheriex EC, Smeets JLRM, Gorgels AP, Wellens HJJ. Value of the 12-lead electrocardiogram at hospital admission in the diagnosis of pulmonary embolism. Am J Cardiol 1999;4:73: 298 – 303. 5. McGinn S, White PD. Acute cor pulmonarly resulting from pulmonary embolism. JAMA 1935;104:1473– 80. 6. Barnes AR. Pulmonary embolism. JAMA 1937;109:1347. 7. Durant TM, Ginsberg IW, Roesler H. Transient bundle branch block and other electrocardiographic changes in pulmonary embolism. Am Heart J 1939;17:423–30. 8. Wood P. Pulmonary embolism: diagnosis by chest lead electrocardiography. Brit Heart J 1941;3:21. 9. Eliaser M, Giansiracusa F. The electrocardiographic diagnosis of acute core pulmonale. Am Heart J 1952;43:533. 10. Sokolov M, Katz LN, Muscovitz AN. The electrocardiogram in pulmonary embolism. Am Heart J 1940;19:166 – 84. 11. Spodick DH. Electrocardiographic responses to pulmonary embolism. Am J Cardiol 1972;30:695. 12. Ferrari E, Inbert A, Darcourt J, et al. No scintigraphic evidence of myocardial abnormality in severe pulmonary embolism with electrocardigraphic signs of anterior ischemia [abstract]. Eur Heart J 1995;16(suppl):269. 13. Yoshinaga T, Ikeda S, Nishimura E, et al. Serial changes in negative T waves on electrocardiography in acute pulmonary thromboembolism. Inetnat J Cardiol 1999;72:65–72. 14. Ferrari E, Imbert A, Chevalier T, Mihouhi A, Morad P, Baudouy M. The electrocardigram in pulmonary embolism: predictive value of negative T waves in precardial leads— 80 case reports. Chest 1997;11:537– 43.

T. C. Chan et al. 15. Cutforth RH, Oram S. The electrocardiogram in pulmonary embolism. Brit Heart Journal 1958;20:41–54. 16. Weber DM, Phillips JH. A re-evaluation of electrocardiographic changes accompanying acute pulmonary embolism. Am J Med Sci 1966;251:381. 17. Szucs MM, Brooks HL, Grossman W, et al. Diagnostic sensitivity of laboratory findings in acute pulmonary embolism 1971;74:161. 18. Sasahara AA, Hyers Tm, Cole Cm, et al. The urokinase–pulmonary embolism trial: a national cooperative study. Circulation 1973;47/48(suppl 2):II-60 –II-65. 19. Stein PD, Dalen JE, McIntyre KM, et al. The electrocardiogram in acute pulmonary embolism. Prog Cardiovasc Dis 1975;14:247–57. 20. Petruzzelli S, Palla A, Pieraccini F, et al. Routine electrocardiography in screening for pulmonary embolism. Respiration 1986;50: 233– 43. 21. Manganelli D, Palla A, Donnamaria V, Giuntini C. Clinical features of pulmonary embolism— doubts and certainties. Chest 1995; 107:25S–32S. 22. Stein PD, Terrin ML, Hales CA, et al. Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest 1991;1000:598 – 603. 23. Rodger M, Makropoulos D, Turek M, et al. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol 2000;86:807–9. 24. Lui CY. Acute pulmonary embolism as the cause of global T wave inversions and QT prolongation. J Electrocardiol 1993; 26:91–5. 25. Lynch RE, Stein PD, Bruce TA. Leftward shift of frontal plane QRS axis as a frequent manifestation of acute pulmonary embolism. Chest 1972;61:443– 6. 26. Nazeyrollas P, Metz D, Jolly D, et al. Use of transthoracic Doppler echocardiography combined with clinical and electrocardiographic data to predict acute pulmonary embolism. Eur Heart J 1996;17: 779 – 86.