David Luke Glancy, MD

When the ST segment is elevated on the electrocardiogram, our first concern is whether the patient is having an ST-segment elevation myocardial infarction (STEMI). However, a number of other conditions can cause ST elevation, and to complicate matters, some of these can coexist with STEMI.

Nevertheless, careful attention to the ST-T and QRS-complex configurations often allows diagnosis of the cause of ST elevation (Figure 1, Table 1). This paper discusses the differential diagnosis of ST elevation.

MEASURED AT THE J POINT OR LATER

ST-segment deviation is usually measured at its junction with the end of the QRS complex, ie, the J point, and is referenced against the TP or PR segment.¹ Some authors prefer measuring the magnitude of the ST deviation 40 to 80 msec after the J point, when all myocardial fibers are expected to have reached the same level of membrane potential and to form an isoelectric ST segment.^2,3

ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

A diagnosis of STEMI that mandates emergency reperfusion requires ST elevation equaling or exceeding the following cut-points, in at least two contiguous leads (using the standardization of 1.0 mV = 10 mm)^4,5:

• 1 mm in all standard leads other than V₂ and V₃
• 2.5 mm in leads V₂ and V₃ in men younger than age 40, 2 mm in leads V₂ and V₃ in men age 40 and older, and 1.5 mm in these leads in women
• 0.5 mm in the posterior chest leads V₇ to V₉; ST elevation is attenuated in the posterior leads because of their greater distance from the heart, explaining the lower cut-point.⁶

While ST elevation that falls below these cut-points may be a normal variant, any ST elevation or depression (≥ 0.5 mm) may be abnormal and may necessitate further evaluation for ischemia, particularly when the clinical setting or the ST morphology suggests ischemia or when other signs of ischemia such as T-wave abnormalities, Q waves, or reciprocal ST-segment changes are also present on the electrocardiogram.

Conversely, ST elevation that exceeds these cut-points may not represent STEMI. In an analysis of patients with chest pain manifesting ST elevation, only 15% were eventually diagnosed with STEMI.⁷ In addition to size, careful attention to the morphology of the ST segment and the associated features is critical (Figure 1).

Other features of STEMI

In STEMI, the ST elevation is typically a convex or a straight oblique line, blending with a wide T wave to form a dome.⁸ But ST elevation may be concave in up to 40% of anterior STEMIs, especially in the early stage.^3,9,10 The nonconcave morphology is highly specific but not sensitive for the diagnosis of anterior STEMI.^3,8,9

Four other features characteristic of STEMI may be present (Figures 2 and 3):

• Concomitant T-wave abnormalities (wide, ample, or inverted T waves)
• Q waves
• ST depression in the reciprocal leads. Reciprocal ST depression is seen in all inferior STEMIs and in 70% of anterior STEMIs.^11,12 Diffuse ST elevation mimicking pericarditis may be seen with midvessel occlusion of a left anterior descending artery that wraps around the apex and supplies part of the inferior wall.

• 

  ST or T-wave amplitude may approximate or exceed the QRS amplitude in at least one lead.^3,13,14 This finding is characteristic of STEMI, in which the QRS “shrinks” as the infarcted area becomes electrically neutral, whereas the ST-T segments become ample.^3,13 In fact, early STEMI may be characterized by a small R wave that seems to be “pulled up” by the elevated ST segment. A small or absent R wave along with an ample, convex ST segment that fuses with the T wave and exceeds the height of the remaining R wave is called “tombstoning” (Figure 3). Tombstoning is most commonly seen with anterior infarction and implies more extensive myocardial damage and a worse prognosis than STEMI without tombstoning.¹⁵

Note that ST elevation may not be acute STEMI but an old STEMI with a chronically dysfunctional myocardium (dyskinetic or aneurysmal myocardium). In fact, an old STEMI may manifest as a chronic, persistent ST elevation along with Q waves, and T waves may be inverted or upright, but not ample.¹⁴ A history of an old MI, old electrocardiograms, if available, and quick bedside echocardiography may allow the diagnosis. In the case of an old dyskinetic infarct, echocardiography shows a thin, bright (scarred), and possibly aneurysmal myocardium, whereas in acute STEMI, the myocardium is neither thin nor scarred yet. If the patient does not report a history of MI, if the T wave is ample (> 75% the size of QRS), or if the patient presents with atypical ongoing angina, presume it is acute STEMI.

 

EARLY REPOLARIZATION

Early repolarization is a normal variant of ST elevation that equals or exceeds 1 mm (measured at the J point). It is highly prevalent in people under age 40 and remains prevalent in middle-aged people.

Two distinct and sometimes coexistent forms of early repolarization have been described: (1) ST elevation in the anterior leads V₁ to V₃,^16–19 and (2) ST elevation in the lateral leads (V₄ to V₆, I, aVL) or inferior leads.^18–22 The prevalence of the first form—ie, ST elevation of 1 mm or more in any of the leads V₁ through V₃—is 60% to 90% in men  age 45 and younger, 20% to 40% in men over age 45, and about 10% in women of any age.¹⁶ Thus, this form of early repolarization is called “normal male pattern.”

Even early repolarization that involves the lateral or inferior leads is common, with a prevalence of about 15% in people ages 30 to 40 and about 5% to 10% in those 40 to 65.^20–23 It is two to four times more prevalent in men and three times more prevalent in African Americans. It is also highly prevalent in athletes younger than 25 (about 30% to 40%).²²

Either way, early repolarization closely resembles the ST elevation of pericarditis and has the following features (Figure 4):

• The ST segment is concave upward, and the J point is well demarcated and may be notched or slurred (Figure 1).
• ST elevation is usually no more than 3 mm.
• ST elevation may be limited to the anterior leads or, in many instances, may extend to the inferior or lateral leads. Early repolarization is very rarely limited to the limb leads, and involvement of some precordial leads is the rule.^18,19 The ST segment is depressed in lead aVR in 50% of patients.^18,19

• 

  The T wave is usually ample and may be more than 10 mm tall in the precordial leads in one-third of patients,¹⁷ but as opposed to the ample T wave of STEMI, it is not broad and remains smaller than the QRS complex. The ample T wave distinguishes early repolarization from pericarditis, and explains the low ST-T ratio in lead V₆. In up to 10% of young black men, the T wave has a terminal inversion in leads V₃ to V₅, and occasionally in V₁ and V₂, mimicking infarction (Figure 5).²⁴
• The QRS complex tends to have prominent precordial voltage, in sharp contrast to STEMI, in which QRS shrinking occurs.^3,17,22

The early repolarization pattern may be intermittent, may vary among serial electrocardiograms, may decrease with a rise in sympathetic tone, as observed during exercise, and may increase with a rise in vagal tone.^18,19,25,26  Although it is usually a benign finding, the early repolarization pattern in leads other than V₁ to V₃ has been associated with an increased risk of sudden death, particularly when the ST elevation is horizontal-descending rather than upsloping and, possibly, when early repolarization involves the inferior leads with a J point that is notched or elevated 2 mm or more.^20,22

PERICARDITIS

In pericarditis, ST elevation is concave upward and is widespread to more than one region without reciprocal ST depression, except for the frequent ST depression in leads aVR and V₁ (64%)²⁷; ST elevation is seldom greater than 4 to 5 mm (Figure 6).^27,28 Since the subepicardial injury is diffuse in pericarditis, the axis of the ST segment follows the anatomic axis of the heart and is generally +45° in the frontal plane. Thus, ST depression is seen in leads aVR and V₁; ST elevation is highest in leads II, V₅, and V₆ and is less in leads III and aVL, where the ST segment may occasionally be depressed.²⁹

Transient PR depression greater than 1 mm is often seen, particularly in leads II, aVF, and V₄ to V₆, and represents atrial subepicardial injury. PR depression in those leads is always associated with PR elevation in lead aVR and sometimes V₁. PR changes often coexist with ST changes but may be isolated and may precede ST changes.³⁰ PR depression is characteristic of pericarditis but may be seen in early repolarization, where it is less marked than in pericarditis (< 0.8 mm) and implies early repolarization of the atrial tissue,³¹ and in MI, where it implies atrial infarction with atrial injury pattern.

Classically, it is said that in pericarditis, unlike in STEMI, the T wave does not invert until the ST elevation subsides. In reality, up to 40% of patients develop a notched or biphasic positive-negative T wave before full return of the ST segment to the baseline.^27,32 And if T-wave inversion antedates pericarditis, concomitant ST elevation and T-wave inversion may be seen once pericarditis develops. However, the T wave inverts less deeply and less completely than in STEMI, and the corrected QT interval remains normal even when the T wave inverts.

Three criteria distinguish pericarditis from early repolarization (but not from STEMI):

• PR depression greater than 1 mm
• ST-segment depression in lead V₁
• A ratio of ST-segment height to T-wave height of at least 25% in lead V₆, V₅, V₄, or I. This feature distinguishes pericarditis from early repolarization with a high sensitivity and specificity. In pericarditis, the T waves have normal or reduced amplitude, and the ST-T ratio is therefore high,³³ whereas in early repolarization the T waves are tall, so the ST-T ratio is less than 25%.

Widespread ST elevation may be seen with both pericarditis and early repolarization. ST elevation limited to the anterior leads is more likely to be early repolarization than pericarditis.

LEFT BUNDLE BRANCH BLOCK

In left bundle branch block, a deep and wide S wave is seen in leads V₁ to V₃ and sometimes in the inferior leads, with ST elevation and T waves that are discordant with the QRS complex—ie, directed opposite to the QRS (Figures 7–9). The ST elevation is typically concave upward.^8,34 Occasionally, ST elevation may be straight or convex, mimicking the dome of STEMI. In the lateral leads, the discordant ST segment is depressed, mimicking a reciprocal ST change.

The following findings imply MI:

• 

  ST elevation or depression that is concordant with the QRS complex. Moreover, since ST deviation is mandatory with left bundle branch block, a “normal-looking” ST segment implies ischemia.
• Inverted T waves concordant with the QRS in more than one lead, or biphasic T waves in more than one lead (eg, V₁ to V₃). Across the precordial leads, T waves may transition from positive to negative one lead earlier or later than the QRS and ST transition. Therefore, even in the absence of ischemia, the T wave may be inverted in lead V₃, in which the QRS is deeply negative and the ST is still elevated (negative T-wave concordance in one lead). Also, the T wave may be upright in leads V₅, V₆, and I where QRS is upright and the ST segment is depressed (positive T-wave concordance does not imply ischemia).

• 

  In addition to concordance, a discordant ST segment or T wave that is very large may imply ischemia. For example, a discordant ST segment or T wave that is larger than the QRS height implies ischemia. A discordant ST elevation greater than 5 mm has been suggested by Sgarbossa et al³⁵ as a diagnostic feature of STEMI; however, this feature is seen in 10% of control patients with left bundle branch block and no STEMI, and it is thus poorly specific and also poorly sensitive, frequently missing STEMI.^35–37 Smith et al³⁶ have suggested that a discordant ST elevation of at least 25% of the S-wave depth is a far more sensitive and accurate feature but one that may still be found in up to 10% of control patients.³⁶

 

LEFT VENTRICULAR HYPERTROPHY

In left ventricular hypertrophy, a deep S wave is seen in leads V₁ to V₃, with ST elevation and T waves that are discordant with the QRS complex. Rarely, ST elevation may be straight or convex. The following findings imply MI:

• ST elevation or depression that is concordant with the QRS.
• Inverted T waves that are concordant with the QRS in more than one lead, or biphasic T waves in more than one lead (eg, V₁ to V₃).
• A discordant ST segment or a T wave that is very large may imply ischemia. In left ventricular hypertrophy, ST elevation is usually less than 2.5 mm in leads V₁ to V₃ and is rarely seen in the inferior leads, where it would be less than 1 mm.³⁴ When ST elevation is seen in leads V₁ to V₃ in left ventricular hypertrophy, an ST magnitude of 25% or more of the total QRS voltage has a 91% specificity for STEMI.³⁴

On another note, right ventricular hypertrophy and right bundle branch block may lead to ST-segment depression and T-wave inversion, but not to ST elevation. Thus, ST elevation occurring with right ventricular hypertrophy or right bundle branch block implies STEMI. While only left bundle branch block poses a diagnostic challenge, both types of bundle branch block, if secondary to STEMI, represent equally high-risk categories.³⁸

PREEXCITATION

Preexcitation may be associated with negative delta waves that mimic Q waves, and with ST elevation in the leads where the negative delta waves are seen, ie, ST elevation discordant with the delta wave (Figure 10). The QRS morphology and the delta wave allow preexcitation to be distinguished from STEMI.

HYPERKALEMIA

The most common finding in hyperkalemia is a peaked, narrow-based T wave that is usually, but not necessarily, tall. ST elevation may be evident in leads V₁ to V₃ (Figure 11). In contrast with hyperkalemia, the T wave of STEMI is typically wide.

OTHER CAUSES OF ST-SEGMENT ELEVATION

Takotsubo cardiomyopathy

Takotsubo cardiomyopathy mimics all electrocardiographic features of anteroapical STEMI. ST elevation may extend to the inferior leads but cannot be isolated in the inferior leads.³⁹ As in apical STEMI, reciprocal ST depression is uncommon. Within 24 to 48 hours, ST elevation evolves into deep anterior T-wave inversion and a prolonged QT interval. Transient Q waves may be seen.

Myocarditis

Myocarditis may have one of two electrocardiographic patterns: a pericarditis pattern, or a typical STEMI pattern with Q waves sometimes localized to one area.⁴⁰

Atrial flutter waves

Atrial flutter waves, particularly of 2:1 atrial flutter, may deform the ST segment so that it mimics an injury pattern on the electrocardiogram. Flutter waves may mimic ST elevation or ST depression (Figure 12).

Large pulmonary embolism

A large pulmonary embolism may be associated with T-wave inversion in the anterior leads or the inferior leads, or both, reflective of cor pulmonale. Less commonly, ST elevation in the anterior or inferior leads is seen. In fact, changes of both anterior and inferior ischemia should always suggest a pulmonary embolism.^41,42

Brugada syndrome

Brugada syndrome is characterized by ST elevation and a right bundle branch block or pseudo-right bundle branch block pattern in at least two of the leads V₁ to V₃. In pseudo-right bundle branch block, the QRS adopts an rSR morphology in the anterior leads but is normal in the lateral leads. Type 1 Brugada pattern, the pattern that is most specifically associated with sudden death, is characterized by a coved, downsloping ST elevation of 2 mm or more with T-wave inversion (Figure 13).⁴³ The Brugada pattern can be transient, triggered by fever, cocaine, or class I antiarrhythmic drugs.

Hyperkalemia, Brugada syndrome, and sometimes pulmonary embolism are characterized by an ST elevation that slopes downward (Figures 11 and 13), which contrasts with the upsloping, convex ST elevation of STEMI.

When the ST segment is elevated on the electrocardiogram, our first concern is whether the patient is having an ST-segment elevation myocardial infarction (STEMI). However, a number of other conditions can cause ST elevation, and to complicate matters, some of these can coexist with STEMI.

Nevertheless, careful attention to the ST-T and QRS-complex configurations often allows diagnosis of the cause of ST elevation (Figure 1, Table 1). This paper discusses the differential diagnosis of ST elevation.

MEASURED AT THE J POINT OR LATER

ST-segment deviation is usually measured at its junction with the end of the QRS complex, ie, the J point, and is referenced against the TP or PR segment.¹ Some authors prefer measuring the magnitude of the ST deviation 40 to 80 msec after the J point, when all myocardial fibers are expected to have reached the same level of membrane potential and to form an isoelectric ST segment.^2,3

ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

A diagnosis of STEMI that mandates emergency reperfusion requires ST elevation equaling or exceeding the following cut-points, in at least two contiguous leads (using the standardization of 1.0 mV = 10 mm)^4,5:

• 1 mm in all standard leads other than V₂ and V₃
• 2.5 mm in leads V₂ and V₃ in men younger than age 40, 2 mm in leads V₂ and V₃ in men age 40 and older, and 1.5 mm in these leads in women
• 0.5 mm in the posterior chest leads V₇ to V₉; ST elevation is attenuated in the posterior leads because of their greater distance from the heart, explaining the lower cut-point.⁶

While ST elevation that falls below these cut-points may be a normal variant, any ST elevation or depression (≥ 0.5 mm) may be abnormal and may necessitate further evaluation for ischemia, particularly when the clinical setting or the ST morphology suggests ischemia or when other signs of ischemia such as T-wave abnormalities, Q waves, or reciprocal ST-segment changes are also present on the electrocardiogram.

Conversely, ST elevation that exceeds these cut-points may not represent STEMI. In an analysis of patients with chest pain manifesting ST elevation, only 15% were eventually diagnosed with STEMI.⁷ In addition to size, careful attention to the morphology of the ST segment and the associated features is critical (Figure 1).

Other features of STEMI

In STEMI, the ST elevation is typically a convex or a straight oblique line, blending with a wide T wave to form a dome.⁸ But ST elevation may be concave in up to 40% of anterior STEMIs, especially in the early stage.^3,9,10 The nonconcave morphology is highly specific but not sensitive for the diagnosis of anterior STEMI.^3,8,9

Four other features characteristic of STEMI may be present (Figures 2 and 3):

• Concomitant T-wave abnormalities (wide, ample, or inverted T waves)
• Q waves
• ST depression in the reciprocal leads. Reciprocal ST depression is seen in all inferior STEMIs and in 70% of anterior STEMIs.^11,12 Diffuse ST elevation mimicking pericarditis may be seen with midvessel occlusion of a left anterior descending artery that wraps around the apex and supplies part of the inferior wall.

• 

  ST or T-wave amplitude may approximate or exceed the QRS amplitude in at least one lead.^3,13,14 This finding is characteristic of STEMI, in which the QRS “shrinks” as the infarcted area becomes electrically neutral, whereas the ST-T segments become ample.^3,13 In fact, early STEMI may be characterized by a small R wave that seems to be “pulled up” by the elevated ST segment. A small or absent R wave along with an ample, convex ST segment that fuses with the T wave and exceeds the height of the remaining R wave is called “tombstoning” (Figure 3). Tombstoning is most commonly seen with anterior infarction and implies more extensive myocardial damage and a worse prognosis than STEMI without tombstoning.¹⁵

Note that ST elevation may not be acute STEMI but an old STEMI with a chronically dysfunctional myocardium (dyskinetic or aneurysmal myocardium). In fact, an old STEMI may manifest as a chronic, persistent ST elevation along with Q waves, and T waves may be inverted or upright, but not ample.¹⁴ A history of an old MI, old electrocardiograms, if available, and quick bedside echocardiography may allow the diagnosis. In the case of an old dyskinetic infarct, echocardiography shows a thin, bright (scarred), and possibly aneurysmal myocardium, whereas in acute STEMI, the myocardium is neither thin nor scarred yet. If the patient does not report a history of MI, if the T wave is ample (> 75% the size of QRS), or if the patient presents with atypical ongoing angina, presume it is acute STEMI.

 

EARLY REPOLARIZATION

Early repolarization is a normal variant of ST elevation that equals or exceeds 1 mm (measured at the J point). It is highly prevalent in people under age 40 and remains prevalent in middle-aged people.

Two distinct and sometimes coexistent forms of early repolarization have been described: (1) ST elevation in the anterior leads V₁ to V₃,^16–19 and (2) ST elevation in the lateral leads (V₄ to V₆, I, aVL) or inferior leads.^18–22 The prevalence of the first form—ie, ST elevation of 1 mm or more in any of the leads V₁ through V₃—is 60% to 90% in men  age 45 and younger, 20% to 40% in men over age 45, and about 10% in women of any age.¹⁶ Thus, this form of early repolarization is called “normal male pattern.”

Even early repolarization that involves the lateral or inferior leads is common, with a prevalence of about 15% in people ages 30 to 40 and about 5% to 10% in those 40 to 65.^20–23 It is two to four times more prevalent in men and three times more prevalent in African Americans. It is also highly prevalent in athletes younger than 25 (about 30% to 40%).²²

Either way, early repolarization closely resembles the ST elevation of pericarditis and has the following features (Figure 4):

• The ST segment is concave upward, and the J point is well demarcated and may be notched or slurred (Figure 1).
• ST elevation is usually no more than 3 mm.
• ST elevation may be limited to the anterior leads or, in many instances, may extend to the inferior or lateral leads. Early repolarization is very rarely limited to the limb leads, and involvement of some precordial leads is the rule.^18,19 The ST segment is depressed in lead aVR in 50% of patients.^18,19

• 

  The T wave is usually ample and may be more than 10 mm tall in the precordial leads in one-third of patients,¹⁷ but as opposed to the ample T wave of STEMI, it is not broad and remains smaller than the QRS complex. The ample T wave distinguishes early repolarization from pericarditis, and explains the low ST-T ratio in lead V₆. In up to 10% of young black men, the T wave has a terminal inversion in leads V₃ to V₅, and occasionally in V₁ and V₂, mimicking infarction (Figure 5).²⁴
• The QRS complex tends to have prominent precordial voltage, in sharp contrast to STEMI, in which QRS shrinking occurs.^3,17,22

The early repolarization pattern may be intermittent, may vary among serial electrocardiograms, may decrease with a rise in sympathetic tone, as observed during exercise, and may increase with a rise in vagal tone.^18,19,25,26  Although it is usually a benign finding, the early repolarization pattern in leads other than V₁ to V₃ has been associated with an increased risk of sudden death, particularly when the ST elevation is horizontal-descending rather than upsloping and, possibly, when early repolarization involves the inferior leads with a J point that is notched or elevated 2 mm or more.^20,22

PERICARDITIS

In pericarditis, ST elevation is concave upward and is widespread to more than one region without reciprocal ST depression, except for the frequent ST depression in leads aVR and V₁ (64%)²⁷; ST elevation is seldom greater than 4 to 5 mm (Figure 6).^27,28 Since the subepicardial injury is diffuse in pericarditis, the axis of the ST segment follows the anatomic axis of the heart and is generally +45° in the frontal plane. Thus, ST depression is seen in leads aVR and V₁; ST elevation is highest in leads II, V₅, and V₆ and is less in leads III and aVL, where the ST segment may occasionally be depressed.²⁹

Transient PR depression greater than 1 mm is often seen, particularly in leads II, aVF, and V₄ to V₆, and represents atrial subepicardial injury. PR depression in those leads is always associated with PR elevation in lead aVR and sometimes V₁. PR changes often coexist with ST changes but may be isolated and may precede ST changes.³⁰ PR depression is characteristic of pericarditis but may be seen in early repolarization, where it is less marked than in pericarditis (< 0.8 mm) and implies early repolarization of the atrial tissue,³¹ and in MI, where it implies atrial infarction with atrial injury pattern.

Classically, it is said that in pericarditis, unlike in STEMI, the T wave does not invert until the ST elevation subsides. In reality, up to 40% of patients develop a notched or biphasic positive-negative T wave before full return of the ST segment to the baseline.^27,32 And if T-wave inversion antedates pericarditis, concomitant ST elevation and T-wave inversion may be seen once pericarditis develops. However, the T wave inverts less deeply and less completely than in STEMI, and the corrected QT interval remains normal even when the T wave inverts.

Three criteria distinguish pericarditis from early repolarization (but not from STEMI):

• PR depression greater than 1 mm
• ST-segment depression in lead V₁
• A ratio of ST-segment height to T-wave height of at least 25% in lead V₆, V₅, V₄, or I. This feature distinguishes pericarditis from early repolarization with a high sensitivity and specificity. In pericarditis, the T waves have normal or reduced amplitude, and the ST-T ratio is therefore high,³³ whereas in early repolarization the T waves are tall, so the ST-T ratio is less than 25%.

Widespread ST elevation may be seen with both pericarditis and early repolarization. ST elevation limited to the anterior leads is more likely to be early repolarization than pericarditis.

LEFT BUNDLE BRANCH BLOCK

In left bundle branch block, a deep and wide S wave is seen in leads V₁ to V₃ and sometimes in the inferior leads, with ST elevation and T waves that are discordant with the QRS complex—ie, directed opposite to the QRS (Figures 7–9). The ST elevation is typically concave upward.^8,34 Occasionally, ST elevation may be straight or convex, mimicking the dome of STEMI. In the lateral leads, the discordant ST segment is depressed, mimicking a reciprocal ST change.

The following findings imply MI:

• 

  ST elevation or depression that is concordant with the QRS complex. Moreover, since ST deviation is mandatory with left bundle branch block, a “normal-looking” ST segment implies ischemia.
• Inverted T waves concordant with the QRS in more than one lead, or biphasic T waves in more than one lead (eg, V₁ to V₃). Across the precordial leads, T waves may transition from positive to negative one lead earlier or later than the QRS and ST transition. Therefore, even in the absence of ischemia, the T wave may be inverted in lead V₃, in which the QRS is deeply negative and the ST is still elevated (negative T-wave concordance in one lead). Also, the T wave may be upright in leads V₅, V₆, and I where QRS is upright and the ST segment is depressed (positive T-wave concordance does not imply ischemia).

• 

  In addition to concordance, a discordant ST segment or T wave that is very large may imply ischemia. For example, a discordant ST segment or T wave that is larger than the QRS height implies ischemia. A discordant ST elevation greater than 5 mm has been suggested by Sgarbossa et al³⁵ as a diagnostic feature of STEMI; however, this feature is seen in 10% of control patients with left bundle branch block and no STEMI, and it is thus poorly specific and also poorly sensitive, frequently missing STEMI.^35–37 Smith et al³⁶ have suggested that a discordant ST elevation of at least 25% of the S-wave depth is a far more sensitive and accurate feature but one that may still be found in up to 10% of control patients.³⁶

 

LEFT VENTRICULAR HYPERTROPHY

In left ventricular hypertrophy, a deep S wave is seen in leads V₁ to V₃, with ST elevation and T waves that are discordant with the QRS complex. Rarely, ST elevation may be straight or convex. The following findings imply MI:

• ST elevation or depression that is concordant with the QRS.
• Inverted T waves that are concordant with the QRS in more than one lead, or biphasic T waves in more than one lead (eg, V₁ to V₃).
• A discordant ST segment or a T wave that is very large may imply ischemia. In left ventricular hypertrophy, ST elevation is usually less than 2.5 mm in leads V₁ to V₃ and is rarely seen in the inferior leads, where it would be less than 1 mm.³⁴ When ST elevation is seen in leads V₁ to V₃ in left ventricular hypertrophy, an ST magnitude of 25% or more of the total QRS voltage has a 91% specificity for STEMI.³⁴

On another note, right ventricular hypertrophy and right bundle branch block may lead to ST-segment depression and T-wave inversion, but not to ST elevation. Thus, ST elevation occurring with right ventricular hypertrophy or right bundle branch block implies STEMI. While only left bundle branch block poses a diagnostic challenge, both types of bundle branch block, if secondary to STEMI, represent equally high-risk categories.³⁸

PREEXCITATION

Preexcitation may be associated with negative delta waves that mimic Q waves, and with ST elevation in the leads where the negative delta waves are seen, ie, ST elevation discordant with the delta wave (Figure 10). The QRS morphology and the delta wave allow preexcitation to be distinguished from STEMI.

HYPERKALEMIA

The most common finding in hyperkalemia is a peaked, narrow-based T wave that is usually, but not necessarily, tall. ST elevation may be evident in leads V₁ to V₃ (Figure 11). In contrast with hyperkalemia, the T wave of STEMI is typically wide.

OTHER CAUSES OF ST-SEGMENT ELEVATION

Takotsubo cardiomyopathy

Takotsubo cardiomyopathy mimics all electrocardiographic features of anteroapical STEMI. ST elevation may extend to the inferior leads but cannot be isolated in the inferior leads.³⁹ As in apical STEMI, reciprocal ST depression is uncommon. Within 24 to 48 hours, ST elevation evolves into deep anterior T-wave inversion and a prolonged QT interval. Transient Q waves may be seen.

Myocarditis

Myocarditis may have one of two electrocardiographic patterns: a pericarditis pattern, or a typical STEMI pattern with Q waves sometimes localized to one area.⁴⁰

Atrial flutter waves

Atrial flutter waves, particularly of 2:1 atrial flutter, may deform the ST segment so that it mimics an injury pattern on the electrocardiogram. Flutter waves may mimic ST elevation or ST depression (Figure 12).

Large pulmonary embolism

A large pulmonary embolism may be associated with T-wave inversion in the anterior leads or the inferior leads, or both, reflective of cor pulmonale. Less commonly, ST elevation in the anterior or inferior leads is seen. In fact, changes of both anterior and inferior ischemia should always suggest a pulmonary embolism.^41,42

Brugada syndrome

Brugada syndrome is characterized by ST elevation and a right bundle branch block or pseudo-right bundle branch block pattern in at least two of the leads V₁ to V₃. In pseudo-right bundle branch block, the QRS adopts an rSR morphology in the anterior leads but is normal in the lateral leads. Type 1 Brugada pattern, the pattern that is most specifically associated with sudden death, is characterized by a coved, downsloping ST elevation of 2 mm or more with T-wave inversion (Figure 13).⁴³ The Brugada pattern can be transient, triggered by fever, cocaine, or class I antiarrhythmic drugs.

Hyperkalemia, Brugada syndrome, and sometimes pulmonary embolism are characterized by an ST elevation that slopes downward (Figures 11 and 13), which contrasts with the upsloping, convex ST elevation of STEMI.

When the ST segment is elevated on the electrocardiogram, our first concern is whether the patient is having an ST-segment elevation myocardial infarction (STEMI). However, a number of other conditions can cause ST elevation, and to complicate matters, some of these can coexist with STEMI.

Nevertheless, careful attention to the ST-T and QRS-complex configurations often allows diagnosis of the cause of ST elevation (Figure 1, Table 1). This paper discusses the differential diagnosis of ST elevation.

MEASURED AT THE J POINT OR LATER

ST-segment deviation is usually measured at its junction with the end of the QRS complex, ie, the J point, and is referenced against the TP or PR segment.¹ Some authors prefer measuring the magnitude of the ST deviation 40 to 80 msec after the J point, when all myocardial fibers are expected to have reached the same level of membrane potential and to form an isoelectric ST segment.^2,3

ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

A diagnosis of STEMI that mandates emergency reperfusion requires ST elevation equaling or exceeding the following cut-points, in at least two contiguous leads (using the standardization of 1.0 mV = 10 mm)^4,5:

• 1 mm in all standard leads other than V₂ and V₃
• 2.5 mm in leads V₂ and V₃ in men younger than age 40, 2 mm in leads V₂ and V₃ in men age 40 and older, and 1.5 mm in these leads in women
• 0.5 mm in the posterior chest leads V₇ to V₉; ST elevation is attenuated in the posterior leads because of their greater distance from the heart, explaining the lower cut-point.⁶

While ST elevation that falls below these cut-points may be a normal variant, any ST elevation or depression (≥ 0.5 mm) may be abnormal and may necessitate further evaluation for ischemia, particularly when the clinical setting or the ST morphology suggests ischemia or when other signs of ischemia such as T-wave abnormalities, Q waves, or reciprocal ST-segment changes are also present on the electrocardiogram.

Conversely, ST elevation that exceeds these cut-points may not represent STEMI. In an analysis of patients with chest pain manifesting ST elevation, only 15% were eventually diagnosed with STEMI.⁷ In addition to size, careful attention to the morphology of the ST segment and the associated features is critical (Figure 1).

Other features of STEMI

In STEMI, the ST elevation is typically a convex or a straight oblique line, blending with a wide T wave to form a dome.⁸ But ST elevation may be concave in up to 40% of anterior STEMIs, especially in the early stage.^3,9,10 The nonconcave morphology is highly specific but not sensitive for the diagnosis of anterior STEMI.^3,8,9

Four other features characteristic of STEMI may be present (Figures 2 and 3):

• Concomitant T-wave abnormalities (wide, ample, or inverted T waves)
• Q waves
• ST depression in the reciprocal leads. Reciprocal ST depression is seen in all inferior STEMIs and in 70% of anterior STEMIs.^11,12 Diffuse ST elevation mimicking pericarditis may be seen with midvessel occlusion of a left anterior descending artery that wraps around the apex and supplies part of the inferior wall.

• 

  ST or T-wave amplitude may approximate or exceed the QRS amplitude in at least one lead.^3,13,14 This finding is characteristic of STEMI, in which the QRS “shrinks” as the infarcted area becomes electrically neutral, whereas the ST-T segments become ample.^3,13 In fact, early STEMI may be characterized by a small R wave that seems to be “pulled up” by the elevated ST segment. A small or absent R wave along with an ample, convex ST segment that fuses with the T wave and exceeds the height of the remaining R wave is called “tombstoning” (Figure 3). Tombstoning is most commonly seen with anterior infarction and implies more extensive myocardial damage and a worse prognosis than STEMI without tombstoning.¹⁵

Note that ST elevation may not be acute STEMI but an old STEMI with a chronically dysfunctional myocardium (dyskinetic or aneurysmal myocardium). In fact, an old STEMI may manifest as a chronic, persistent ST elevation along with Q waves, and T waves may be inverted or upright, but not ample.¹⁴ A history of an old MI, old electrocardiograms, if available, and quick bedside echocardiography may allow the diagnosis. In the case of an old dyskinetic infarct, echocardiography shows a thin, bright (scarred), and possibly aneurysmal myocardium, whereas in acute STEMI, the myocardium is neither thin nor scarred yet. If the patient does not report a history of MI, if the T wave is ample (> 75% the size of QRS), or if the patient presents with atypical ongoing angina, presume it is acute STEMI.

 

EARLY REPOLARIZATION

Early repolarization is a normal variant of ST elevation that equals or exceeds 1 mm (measured at the J point). It is highly prevalent in people under age 40 and remains prevalent in middle-aged people.

Two distinct and sometimes coexistent forms of early repolarization have been described: (1) ST elevation in the anterior leads V₁ to V₃,^16–19 and (2) ST elevation in the lateral leads (V₄ to V₆, I, aVL) or inferior leads.^18–22 The prevalence of the first form—ie, ST elevation of 1 mm or more in any of the leads V₁ through V₃—is 60% to 90% in men  age 45 and younger, 20% to 40% in men over age 45, and about 10% in women of any age.¹⁶ Thus, this form of early repolarization is called “normal male pattern.”

Even early repolarization that involves the lateral or inferior leads is common, with a prevalence of about 15% in people ages 30 to 40 and about 5% to 10% in those 40 to 65.^20–23 It is two to four times more prevalent in men and three times more prevalent in African Americans. It is also highly prevalent in athletes younger than 25 (about 30% to 40%).²²

Either way, early repolarization closely resembles the ST elevation of pericarditis and has the following features (Figure 4):

• The ST segment is concave upward, and the J point is well demarcated and may be notched or slurred (Figure 1).
• ST elevation is usually no more than 3 mm.
• ST elevation may be limited to the anterior leads or, in many instances, may extend to the inferior or lateral leads. Early repolarization is very rarely limited to the limb leads, and involvement of some precordial leads is the rule.^18,19 The ST segment is depressed in lead aVR in 50% of patients.^18,19

• 

  The T wave is usually ample and may be more than 10 mm tall in the precordial leads in one-third of patients,¹⁷ but as opposed to the ample T wave of STEMI, it is not broad and remains smaller than the QRS complex. The ample T wave distinguishes early repolarization from pericarditis, and explains the low ST-T ratio in lead V₆. In up to 10% of young black men, the T wave has a terminal inversion in leads V₃ to V₅, and occasionally in V₁ and V₂, mimicking infarction (Figure 5).²⁴
• The QRS complex tends to have prominent precordial voltage, in sharp contrast to STEMI, in which QRS shrinking occurs.^3,17,22

The early repolarization pattern may be intermittent, may vary among serial electrocardiograms, may decrease with a rise in sympathetic tone, as observed during exercise, and may increase with a rise in vagal tone.^18,19,25,26  Although it is usually a benign finding, the early repolarization pattern in leads other than V₁ to V₃ has been associated with an increased risk of sudden death, particularly when the ST elevation is horizontal-descending rather than upsloping and, possibly, when early repolarization involves the inferior leads with a J point that is notched or elevated 2 mm or more.^20,22

PERICARDITIS

In pericarditis, ST elevation is concave upward and is widespread to more than one region without reciprocal ST depression, except for the frequent ST depression in leads aVR and V₁ (64%)²⁷; ST elevation is seldom greater than 4 to 5 mm (Figure 6).^27,28 Since the subepicardial injury is diffuse in pericarditis, the axis of the ST segment follows the anatomic axis of the heart and is generally +45° in the frontal plane. Thus, ST depression is seen in leads aVR and V₁; ST elevation is highest in leads II, V₅, and V₆ and is less in leads III and aVL, where the ST segment may occasionally be depressed.²⁹

Transient PR depression greater than 1 mm is often seen, particularly in leads II, aVF, and V₄ to V₆, and represents atrial subepicardial injury. PR depression in those leads is always associated with PR elevation in lead aVR and sometimes V₁. PR changes often coexist with ST changes but may be isolated and may precede ST changes.³⁰ PR depression is characteristic of pericarditis but may be seen in early repolarization, where it is less marked than in pericarditis (< 0.8 mm) and implies early repolarization of the atrial tissue,³¹ and in MI, where it implies atrial infarction with atrial injury pattern.

Classically, it is said that in pericarditis, unlike in STEMI, the T wave does not invert until the ST elevation subsides. In reality, up to 40% of patients develop a notched or biphasic positive-negative T wave before full return of the ST segment to the baseline.^27,32 And if T-wave inversion antedates pericarditis, concomitant ST elevation and T-wave inversion may be seen once pericarditis develops. However, the T wave inverts less deeply and less completely than in STEMI, and the corrected QT interval remains normal even when the T wave inverts.

Three criteria distinguish pericarditis from early repolarization (but not from STEMI):

• PR depression greater than 1 mm
• ST-segment depression in lead V₁
• A ratio of ST-segment height to T-wave height of at least 25% in lead V₆, V₅, V₄, or I. This feature distinguishes pericarditis from early repolarization with a high sensitivity and specificity. In pericarditis, the T waves have normal or reduced amplitude, and the ST-T ratio is therefore high,³³ whereas in early repolarization the T waves are tall, so the ST-T ratio is less than 25%.

Widespread ST elevation may be seen with both pericarditis and early repolarization. ST elevation limited to the anterior leads is more likely to be early repolarization than pericarditis.

LEFT BUNDLE BRANCH BLOCK

In left bundle branch block, a deep and wide S wave is seen in leads V₁ to V₃ and sometimes in the inferior leads, with ST elevation and T waves that are discordant with the QRS complex—ie, directed opposite to the QRS (Figures 7–9). The ST elevation is typically concave upward.^8,34 Occasionally, ST elevation may be straight or convex, mimicking the dome of STEMI. In the lateral leads, the discordant ST segment is depressed, mimicking a reciprocal ST change.

The following findings imply MI:

• 

  ST elevation or depression that is concordant with the QRS complex. Moreover, since ST deviation is mandatory with left bundle branch block, a “normal-looking” ST segment implies ischemia.
• Inverted T waves concordant with the QRS in more than one lead, or biphasic T waves in more than one lead (eg, V₁ to V₃). Across the precordial leads, T waves may transition from positive to negative one lead earlier or later than the QRS and ST transition. Therefore, even in the absence of ischemia, the T wave may be inverted in lead V₃, in which the QRS is deeply negative and the ST is still elevated (negative T-wave concordance in one lead). Also, the T wave may be upright in leads V₅, V₆, and I where QRS is upright and the ST segment is depressed (positive T-wave concordance does not imply ischemia).

• 

  In addition to concordance, a discordant ST segment or T wave that is very large may imply ischemia. For example, a discordant ST segment or T wave that is larger than the QRS height implies ischemia. A discordant ST elevation greater than 5 mm has been suggested by Sgarbossa et al³⁵ as a diagnostic feature of STEMI; however, this feature is seen in 10% of control patients with left bundle branch block and no STEMI, and it is thus poorly specific and also poorly sensitive, frequently missing STEMI.^35–37 Smith et al³⁶ have suggested that a discordant ST elevation of at least 25% of the S-wave depth is a far more sensitive and accurate feature but one that may still be found in up to 10% of control patients.³⁶

 

LEFT VENTRICULAR HYPERTROPHY

In left ventricular hypertrophy, a deep S wave is seen in leads V₁ to V₃, with ST elevation and T waves that are discordant with the QRS complex. Rarely, ST elevation may be straight or convex. The following findings imply MI:

• ST elevation or depression that is concordant with the QRS.
• Inverted T waves that are concordant with the QRS in more than one lead, or biphasic T waves in more than one lead (eg, V₁ to V₃).
• A discordant ST segment or a T wave that is very large may imply ischemia. In left ventricular hypertrophy, ST elevation is usually less than 2.5 mm in leads V₁ to V₃ and is rarely seen in the inferior leads, where it would be less than 1 mm.³⁴ When ST elevation is seen in leads V₁ to V₃ in left ventricular hypertrophy, an ST magnitude of 25% or more of the total QRS voltage has a 91% specificity for STEMI.³⁴

On another note, right ventricular hypertrophy and right bundle branch block may lead to ST-segment depression and T-wave inversion, but not to ST elevation. Thus, ST elevation occurring with right ventricular hypertrophy or right bundle branch block implies STEMI. While only left bundle branch block poses a diagnostic challenge, both types of bundle branch block, if secondary to STEMI, represent equally high-risk categories.³⁸

PREEXCITATION

Preexcitation may be associated with negative delta waves that mimic Q waves, and with ST elevation in the leads where the negative delta waves are seen, ie, ST elevation discordant with the delta wave (Figure 10). The QRS morphology and the delta wave allow preexcitation to be distinguished from STEMI.

HYPERKALEMIA

The most common finding in hyperkalemia is a peaked, narrow-based T wave that is usually, but not necessarily, tall. ST elevation may be evident in leads V₁ to V₃ (Figure 11). In contrast with hyperkalemia, the T wave of STEMI is typically wide.

OTHER CAUSES OF ST-SEGMENT ELEVATION

Takotsubo cardiomyopathy

Takotsubo cardiomyopathy mimics all electrocardiographic features of anteroapical STEMI. ST elevation may extend to the inferior leads but cannot be isolated in the inferior leads.³⁹ As in apical STEMI, reciprocal ST depression is uncommon. Within 24 to 48 hours, ST elevation evolves into deep anterior T-wave inversion and a prolonged QT interval. Transient Q waves may be seen.

Myocarditis

Myocarditis may have one of two electrocardiographic patterns: a pericarditis pattern, or a typical STEMI pattern with Q waves sometimes localized to one area.⁴⁰

Atrial flutter waves

Atrial flutter waves, particularly of 2:1 atrial flutter, may deform the ST segment so that it mimics an injury pattern on the electrocardiogram. Flutter waves may mimic ST elevation or ST depression (Figure 12).

Large pulmonary embolism

A large pulmonary embolism may be associated with T-wave inversion in the anterior leads or the inferior leads, or both, reflective of cor pulmonale. Less commonly, ST elevation in the anterior or inferior leads is seen. In fact, changes of both anterior and inferior ischemia should always suggest a pulmonary embolism.^41,42

Brugada syndrome

Brugada syndrome is characterized by ST elevation and a right bundle branch block or pseudo-right bundle branch block pattern in at least two of the leads V₁ to V₃. In pseudo-right bundle branch block, the QRS adopts an rSR morphology in the anterior leads but is normal in the lateral leads. Type 1 Brugada pattern, the pattern that is most specifically associated with sudden death, is characterized by a coved, downsloping ST elevation of 2 mm or more with T-wave inversion (Figure 13).⁴³ The Brugada pattern can be transient, triggered by fever, cocaine, or class I antiarrhythmic drugs.

Hyperkalemia, Brugada syndrome, and sometimes pulmonary embolism are characterized by an ST elevation that slopes downward (Figures 11 and 13), which contrasts with the upsloping, convex ST elevation of STEMI.

Depression of the ST segment and inversion of the T wave are common electrocardiographic abnormalities. Knowing the various ischemic and nonischemic morphologic features is critical for a timely diagnosis of high-risk myocardial ischemia and electrolyte- or drug-related abnormalities. Moreover, it is important to recognize that true posterior infarction or subtle ST-segment elevation infarction may masquerade as ST-segment depression ischemia, and that pulmonary embolism may masquerade as anterior ischemia. These common electrocardiographic abnormalities are summarized in Table 1.

THE ST SEGMENT AND THE T WAVE: A PRIMER

Abnormalities of the ST segment and the T wave represent abnormalities of ventricular repolarization.

The ST segment corresponds to the plateau phase of ventricular repolarization (phase 2 of the action potential), while the T wave corresponds to the phase of rapid ventricular repolarization (phase 3). ST-segment or T-wave changes may be secondary to abnormalities of depolarization, ie, pre-excitation or abnormalities of QRS voltage or duration.

On the other hand, ST-segment and T-wave abnormalities may be unrelated to any QRS abnormality, in which case they are called primary repolarization abnormalities. These are caused by ischemia, pericarditis, myocarditis, drugs (digoxin, antiarrhythmic drugs), and electrolyte abnormalities, particularly potassium abnormalities.

ST-segment deviation is usually measured at its junction with the end of the QRS complex, ie, the J point, and is referenced against the TP or PR segment.¹ But some prefer to measure the magnitude of the ST-segment deviation 40 to 80 ms after the J point, when all myocardial fibers are expected to have reached the same level of membrane potential and to form an isoelectric ST segment; at the very onset of repolarization, small differences in membrane potential may normally be seen and may cause deviation of the J point and of the early portion of the ST segment.²

Although a diagnosis of ST-segment elevation myocardial infarction (STEMI) that mandates emergency reperfusion therapy requires ST-segment elevation greater than 1 mm in at least two contiguous leads,³ any ST-segment depression or elevation (≥ 0.5 mm, using the usual standard of 1.0 mV = 10 mm) may be abnormal, particularly when the clinical context or the shape of the ST segment suggests ischemia, or when other ischemic signs such as T-wave abnormalities, Q waves, or reciprocal ST-segment changes are concomitantly present. On the other hand, ST-segment depression of up to 0.5 mm in leads V₂ and V₃ and 1 mm in the other leads may be normal.¹

In adults, the T wave normally is inverted in lead aVR; is upright or inverted in leads aVL, III, and V₁; and is upright in leads I, II, aVF, and V₂ through V₆. The T wave is considered inverted when it is deeper than 1 mm; it is considered flat when its peak amplitude is between 1.0 mm and −1.0 mm.¹

As we will discuss, certain features allow the various causes of ST-segment and T-wave abnormalities to be distinguished from one another.

SECONDARY ST-SEGMENT AND T-WAVE ABNORMALITIES

Modified with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrubhill Press; 2009:328–354.

In secondary ST-segment or T-wave abnormalities, QRS criteria for left or right ventricular hypertrophy or left or right bundle branch block or pre-excitation are usually present, and the ST segment and T wave have all of the following morphologic features (Figure 1A):

• The ST segment and T wave are directed opposite to the QRS: this is called discordance between the QRS complex and the ST-T abnormalities. In the case of right bundle branch block, the ST and T are directed opposite to the terminal portion of the QRS, ie, the part of the QRS deformed by the conduction abnormality.
• The ST segment and T wave are both abnormal and deviate in the same direction, ie, the ST segment is down-sloping and the T wave is inverted in leads with an upright QRS complex, which gives the ST-T complex a “reverse checkmark” asymmetric morphology.
• The ST and T abnormalities are not dynamic, ie, they do not change in the course of several hours to several days.

Thus, in cases of left ventricular hypertrophy or left bundle branch block, since the QRS complex is upright in the left lateral leads I, aVL, V₅, and V₆, the ST segment is characteristically depressed and the T wave is inverted in these leads (Figure 2). In cases of right ventricular hypertrophy or right bundle branch block, T waves are characteristically inverted in the right precordial leads V₁, V₂, and V₃.

Left bundle branch block is always associated with secondary ST-T abnormalities, the absence of which suggests associated ischemia. Left and right ventricular hypertrophy, on the other hand, are not always associated with ST-T abnormalities, but when these are present, they correlate with more severe hypertrophy or ventricular systolic dysfunction,⁴ and have been called strain pattern. In addition, while these morphologic features are consistent with secondary abnormalities, they do not rule out ischemia in a patient with angina.

Some exceptions to these typical morphologic features:

• Right ventricular hypertrophy and right bundle branch block may be associated with isolated T-wave inversion without ST-segment depression in precordial leads V₁, V₂, and V₃.
• Left ventricular hypertrophy may be associated with symmetric T-wave inversion without ST-segment depression or with a horizontally depressed ST segment. This may be the case in up to one-third of ST-T abnormalities secondary to left ventricular hypertrophy and is seen in hypertrophic cardiomyopathy, particularly the apical variant, in leads V₃ through V₆.⁵

 

ISCHEMIC ST-SEGMENT DEPRESSION, T-WAVE INVERSION, OR BOTH

ST-segment depression or T-wave inversion is consistent with ischemia if any of the following is true:

• The ST-segment depression or T-wave inversion is directed in the same direction as the QRS complex: this is called concordance between the QRS complex and the ST or T abnormality (Figure 1B).
• The ST segment is depressed but the T wave is upright (Figure 1C).
• The T wave has a positive-negative biphasic pattern (Figure 1D).
• The T wave is symmetrically inverted and has a pointed configuration, while the ST segment is not deviated or is upwardly bowed (coved) or horizontally depressed (Figure 1E).
• The magnitude of ST-segment depression progresses or regresses on serial tracings, or ST-segment depression progresses to T-wave abnormality during ischemia-free intervals (dynamic ST-segment depression).

Unlike ST-segment elevation, ST-segment depression does not localize ischemia.⁶ However, the extent and the magnitude of ST-segment depression correlate with the extent and the severity of ischemia. In fact, ST-segment depression in eight or more leads, combined with ST-segment elevation in leads aVR and V₁ and occurring during ischemic pain, is associated with a 75% predictive accuracy for left main coronary artery or three-vessel disease (Figure 3).^7,8 This finding may also be seen in cases of tight proximal stenosis of the left anterior descending coronary artery.⁹

Wellens syndrome

Either the positive-negative biphasic T waves of the type shown in Figure 1D or the deeply inverted (≥ 5 mm) T waves that often follow them, when occurring in the precordial leads V₂ and V₃, with or without similar changes in V₁, V₄, and V₅, are nearly pathognomonic of very recent severe ischemia or injury in the distribution of the left anterior descending artery and characterize what is known as Wellens syndrome (Figure 4).^10–13

Wellens and his colleagues showed that 75% of patients who developed these T-wave abnormalities and who were treated medically without angiographic investigation went on to develop extensive anterior wall myocardial infarction within a mean of 8.5 days.¹⁰

In a later investigation of 1,260 patients presenting with unstable angina, 180 patients (14%) had this characteristic T-wave pattern.¹¹ All of the latter patients had stenosis of 50% or more in the proximal left anterior descending artery, and 18% had total occlusion of the left anterior descending artery.

Thus, although medical management may provide symptomatic improvement at first, early coronary angiography and revascularization should be strongly considered in anyone with Wellens syndrome because it usually predicts impending anterior myocardial infarction.

Wellens syndrome is characterized by two patterns of T-wave changes. In 75% of cases, T waves are deeply (≥ 5 mm) and symmetrically inverted in leads V₂ through V₄ (Figures 1E, 4B). In 25% of cases, the T wave has a characteristic positive-negative biphasic morphology in leads V₂ through V₄ (Figures 1D, 4A).¹⁰ In both patterns, the ST segment is isoelectric or minimally elevated (< 1 mm) with a straight or convex morphology, the down-slope of the T wave is sharp, and the QT interval is often prolonged. These abnormalities are characteristically seen hours to days after the ischemic chest pain resolves. In fact, the ischemic episode is usually associated with transient ST-segment elevation or depression that progresses to the T-wave abnormality after the pain subsides.¹¹

In Wellens’ original description, only 12% of patients had increases in their creatine kinase levels, and these were small. Therefore, the electrocardiogram may be the only indication of an impending large anterior infarction in a chest-pain-free patient.¹²

T waves that are symmetrically but less deeply inverted than Wellens-type T waves may still represent ischemia. However, this finding is less specific for ischemia and is associated with better outcomes than Wellens syndrome or ST-segment deviation, particularly when the T wave is less than 3 mm deep.¹⁴ In fact, one prospective cohort study found that isolated mild T-wave inversion in patients presenting with acute coronary syndrome is associated with a favorable long-term outcome, similar to that in patients with no electrocardiographic changes.¹⁵

FREQUENTLY MISSED DIAGNOSES MANIFESTING AS ST-SEGMENT DEPRESSION OR T-WAVE INVERSION

True posterior ST-segment elevation myocardial infarction

When accompanied by inferior STEMI, posterior infarction is easily recognized, but it can be difficult to diagnose when it occurs alone, the so-called true posterior STEMI.

ST-segment depression that is most prominent in leads V₁ through V₃ often indicates posterior STEMI rather than non–ST-segment elevation ischemia and indicates the need for emergency revascularization. In fact, in the setting of posterior infarction, leads V₁, V₂, and V₃ predominate as the areas of maximum depression, whereas greater ST-segment depression in the lateral precordial leads (V₄, V₅, and V₆) or inferior leads (II, III, and aVF) is more indicative of nonocclusive and nonregional subendocardial ischemia (Figure 5).^8,16–18

In most cases of posterior infarction, the posterior chest leads V₇, V₈, and V₉ reveal ST-segment elevation.¹⁹ One study found that ST-segment depression in the anterior precordial leads was as sensitive as ST-segment elevation in leads V₇ through V₉ in identifying posterior myocardial infarction (sensitivity 80%),²⁰ while other studies found that ST-segment deviation on standard 12-lead electrocardiography has a lower sensitivity (about 60%) in identifying posterior infarction.^18,21

Tall or wide (≥ 0.04-s) R waves in leads V₁ or V₂, particularly when associated with upright T waves, suggest posterior infarction and may further corroborate this diagnosis, but this finding may take up to 24 hours to manifest and is seen in only about 50% of patients with posterior infarction.²¹

Studies have shown that ST-segment elevation on standard 12-lead electrocardiography is found in fewer than 50% of patients with acute left circumflex occlusion and inferoposterior infarction,¹⁸ yet these are cases of “missed” STEMI that indeed benefit from emergency angiography and reperfusion. In addition, studies of non–ST-segment elevation acute coronary syndrome consistently identify patients who have epicardial vessel occlusion (about 15%–20% of cases),¹⁸ yet their initial angiography is usually delayed for hours or days after the initial presentation.

A subgroup analysis from TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction 38) evaluated patients with isolated anterior ST-segment depression. An occluded “culprit” artery was found 26% of the time, most often the left circumflex artery. Moreover, those patients had a significantly higher rate of death or myocardial infarction at 30-day follow-up than patients without a culprit artery, probably related to delayed revascularization.²²

Recognizing that ST-segment depression that is greatest in leads V₁, V₂, or V₃ represents posterior infarction helps identify a portion of the missed STEMIs in a timely fashion. In addition, in cases of anterior ST-segment depression and in cases of chest pain with nondiagnostic electrocardiography, the recording of ST elevation in leads V₇, V₈, and V₉ is highly sensitive for detecting a true posterior injury.

 

 

Acute pulmonary embolism

An anterior ischemic pattern of symmetric T-wave inversion in the precordial leads V₁ through V₄ may also be a sign of acute or chronic right ventricular strain, particularly acute pulmonary embolism. Sinus tachycardia is usually present, but other signs of pulmonary embolism, such as right ventricular hypertrophy and right bundle branch block, may be absent. In fact, T-wave inversion in leads V₁ through V₄ is noted in 19% of patients with nonmassive pulmonary embolism and in 85% of patients with massive pulmonary embolism, and is the most sensitive and specific electrocardiographic finding in massive pulmonary embolism.²³

In addition, acute pulmonary embolism may be associated with T-wave inversion in leads III and aVF,²⁴ and changes of concomitant anterior and inferior ischemia should always raise the question of this diagnosis.

In one retrospective study of patients with acute pulmonary embolism, nonspecific ST-segment or T-wave changes were the most common finding on electrocardiography, noted in 49%.²⁵ Rapid regression of these changes on serial tracings favors pulmonary embolism rather than myocardial infarction.

ST-segment depression reciprocal to a subtle ST-segment elevation

When ST-segment elevation occurs in two contiguous standard leads while ST-segment depression occurs in other leads, and when the ST-segment and T-wave abnormalities are ischemic rather than secondary to depolarization abnormalities, ST-segment elevation is considered the primary ischemic abnormality whereas ST-segment depression is often considered a reciprocal “mirror image” change. This “reciprocal” change may also represent remote ischemia in a distant territory in patients with multivessel coronary disease.^26,27

Reciprocal ST-segment depression is present in all patients with inferior myocardial infarction and in 70% of patients with anterior myocardial infarction.²⁸

However, it is important to recognize that the magnitude of ST-segment elevation and reciprocal ST-segment depression is affected by the distance of the leads recording these changes from the ischemic region and their angle of deviation from the ischemic region.²⁹ This explains why occasionally—and particularly when the overall amplitude of the QRS complex is low—the magnitude of ST-segment elevation is small, whereas the reciprocal ST-segment depression is more prominent. In fact, in the absence of left ventricular hypertrophy or left bundle branch block, the reciprocal ST-segment depression should be sought. It is of great utility in patients with acute cardiac symptoms and mild elevation of ST segments of 1 to 1.5 mm in two contiguous leads, as it strongly suggests the diagnosis of STEMI rather than other causes of mild ST-segment elevation (1–1.5 mm) (Figure 6).³⁰ The less-pronounced ST-segment elevation is often overlooked, and the patient is erroneously diagnosed with non–ST-segment elevation acute coronary syndrome rather than STEMI. This has a marked impact on patient management, as STEMI requires emergency revascularization, while non–ST-segment elevation ischemia requires early (but not emergency) coronary angiography.

Hypokalemia and digitalis effect

ST-segment depression, T-wave flattening, and prominent U waves are the hallmarks of hypokalemia and can be mistaken for ischemic changes, including ischemic lengthening of the QT interval (Figure 7).^31–34 Digitalis also produces ST-segment depression, low or inverted T waves, and prominent U waves, but the U waves rarely are of the giant variety seen with severe hypokalemia, and the ST-segment depression has a sagging shape. In addition, digitalis shortens the QT interval.

DIFFUSE (GLOBAL) T-WAVE INVERSION

Reproduced with permission from Glancy DL, et al. Global T-wave inversion in a 77-year-old woman. Proc (Bayl Univ Med Cent) 2009; 22:81–82.

This term is applied when the T wave is inverted in most of the standard leads except aVR, which shows a reciprocal upright T wave. The QT interval is often prolonged, and T-wave inversion is often symmetric and “giant” (> 10 mm) (Figure 8).^1,35

Walder and Spodick³⁶ have found this pattern to be caused most often by myocardial ischemia or neurologic events, particularly intracranial hemorrhage, and it seems more prevalent in women. Other causes include hypertrophic cardiomyopathy, stress-induced cardiomyopathy (takotsubo cardiomyopathy), cocaine abuse, pericarditis, pulmonary embolism, and advanced or complete atrioventricular block.^36,37

The prognosis in patients with global T-wave inversion is determined by the underlying disease, and the striking T-wave changes per se do not imply a poor prognosis.³⁸

Of note, takotsubo cardiomyopathy is characterized by electrocardiographic changes that mimic ischemia, especially STEMI, and is often impossible to differentiate from myocardial ischemia related to a coronary event without performing coronary arteriography. The most common abnormality on the admission electrocardiogram is ST-segment elevation (present in 46%–100% of patients), typically seen in the precordial leads. Within 48 hours of presentation, almost all patients also develop postischemic diffuse T-wave inversion and prolongation of the QT interval. New Q waves may be seen in 6% to 31% of patients and are usually transient.^39,40

OTHER CAUSES OF T-WAVE INVERSION OR ST-SEGMENT DEPRESSION

Various other entities may cause T-wave inversion, notably acute pericarditis or myocarditis, ^41,42 memory T-wave phenomenon,^43,44 and normal variants of repolarization (Table 1, Figure 9).⁴⁵ Additionally, a nonpathologic junctional ST-segment depression may be seen in tachycardia (Figure 10).

Depression of the ST segment and inversion of the T wave are common electrocardiographic abnormalities. Knowing the various ischemic and nonischemic morphologic features is critical for a timely diagnosis of high-risk myocardial ischemia and electrolyte- or drug-related abnormalities. Moreover, it is important to recognize that true posterior infarction or subtle ST-segment elevation infarction may masquerade as ST-segment depression ischemia, and that pulmonary embolism may masquerade as anterior ischemia. These common electrocardiographic abnormalities are summarized in Table 1.

THE ST SEGMENT AND THE T WAVE: A PRIMER

Abnormalities of the ST segment and the T wave represent abnormalities of ventricular repolarization.

The ST segment corresponds to the plateau phase of ventricular repolarization (phase 2 of the action potential), while the T wave corresponds to the phase of rapid ventricular repolarization (phase 3). ST-segment or T-wave changes may be secondary to abnormalities of depolarization, ie, pre-excitation or abnormalities of QRS voltage or duration.

On the other hand, ST-segment and T-wave abnormalities may be unrelated to any QRS abnormality, in which case they are called primary repolarization abnormalities. These are caused by ischemia, pericarditis, myocarditis, drugs (digoxin, antiarrhythmic drugs), and electrolyte abnormalities, particularly potassium abnormalities.

ST-segment deviation is usually measured at its junction with the end of the QRS complex, ie, the J point, and is referenced against the TP or PR segment.¹ But some prefer to measure the magnitude of the ST-segment deviation 40 to 80 ms after the J point, when all myocardial fibers are expected to have reached the same level of membrane potential and to form an isoelectric ST segment; at the very onset of repolarization, small differences in membrane potential may normally be seen and may cause deviation of the J point and of the early portion of the ST segment.²

Although a diagnosis of ST-segment elevation myocardial infarction (STEMI) that mandates emergency reperfusion therapy requires ST-segment elevation greater than 1 mm in at least two contiguous leads,³ any ST-segment depression or elevation (≥ 0.5 mm, using the usual standard of 1.0 mV = 10 mm) may be abnormal, particularly when the clinical context or the shape of the ST segment suggests ischemia, or when other ischemic signs such as T-wave abnormalities, Q waves, or reciprocal ST-segment changes are concomitantly present. On the other hand, ST-segment depression of up to 0.5 mm in leads V₂ and V₃ and 1 mm in the other leads may be normal.¹

In adults, the T wave normally is inverted in lead aVR; is upright or inverted in leads aVL, III, and V₁; and is upright in leads I, II, aVF, and V₂ through V₆. The T wave is considered inverted when it is deeper than 1 mm; it is considered flat when its peak amplitude is between 1.0 mm and −1.0 mm.¹

As we will discuss, certain features allow the various causes of ST-segment and T-wave abnormalities to be distinguished from one another.

SECONDARY ST-SEGMENT AND T-WAVE ABNORMALITIES

Modified with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrubhill Press; 2009:328–354.

In secondary ST-segment or T-wave abnormalities, QRS criteria for left or right ventricular hypertrophy or left or right bundle branch block or pre-excitation are usually present, and the ST segment and T wave have all of the following morphologic features (Figure 1A):

• The ST segment and T wave are directed opposite to the QRS: this is called discordance between the QRS complex and the ST-T abnormalities. In the case of right bundle branch block, the ST and T are directed opposite to the terminal portion of the QRS, ie, the part of the QRS deformed by the conduction abnormality.
• The ST segment and T wave are both abnormal and deviate in the same direction, ie, the ST segment is down-sloping and the T wave is inverted in leads with an upright QRS complex, which gives the ST-T complex a “reverse checkmark” asymmetric morphology.
• The ST and T abnormalities are not dynamic, ie, they do not change in the course of several hours to several days.

Thus, in cases of left ventricular hypertrophy or left bundle branch block, since the QRS complex is upright in the left lateral leads I, aVL, V₅, and V₆, the ST segment is characteristically depressed and the T wave is inverted in these leads (Figure 2). In cases of right ventricular hypertrophy or right bundle branch block, T waves are characteristically inverted in the right precordial leads V₁, V₂, and V₃.

Left bundle branch block is always associated with secondary ST-T abnormalities, the absence of which suggests associated ischemia. Left and right ventricular hypertrophy, on the other hand, are not always associated with ST-T abnormalities, but when these are present, they correlate with more severe hypertrophy or ventricular systolic dysfunction,⁴ and have been called strain pattern. In addition, while these morphologic features are consistent with secondary abnormalities, they do not rule out ischemia in a patient with angina.

Some exceptions to these typical morphologic features:

• Right ventricular hypertrophy and right bundle branch block may be associated with isolated T-wave inversion without ST-segment depression in precordial leads V₁, V₂, and V₃.
• Left ventricular hypertrophy may be associated with symmetric T-wave inversion without ST-segment depression or with a horizontally depressed ST segment. This may be the case in up to one-third of ST-T abnormalities secondary to left ventricular hypertrophy and is seen in hypertrophic cardiomyopathy, particularly the apical variant, in leads V₃ through V₆.⁵

 

ISCHEMIC ST-SEGMENT DEPRESSION, T-WAVE INVERSION, OR BOTH

ST-segment depression or T-wave inversion is consistent with ischemia if any of the following is true:

• The ST-segment depression or T-wave inversion is directed in the same direction as the QRS complex: this is called concordance between the QRS complex and the ST or T abnormality (Figure 1B).
• The ST segment is depressed but the T wave is upright (Figure 1C).
• The T wave has a positive-negative biphasic pattern (Figure 1D).
• The T wave is symmetrically inverted and has a pointed configuration, while the ST segment is not deviated or is upwardly bowed (coved) or horizontally depressed (Figure 1E).
• The magnitude of ST-segment depression progresses or regresses on serial tracings, or ST-segment depression progresses to T-wave abnormality during ischemia-free intervals (dynamic ST-segment depression).

Unlike ST-segment elevation, ST-segment depression does not localize ischemia.⁶ However, the extent and the magnitude of ST-segment depression correlate with the extent and the severity of ischemia. In fact, ST-segment depression in eight or more leads, combined with ST-segment elevation in leads aVR and V₁ and occurring during ischemic pain, is associated with a 75% predictive accuracy for left main coronary artery or three-vessel disease (Figure 3).^7,8 This finding may also be seen in cases of tight proximal stenosis of the left anterior descending coronary artery.⁹

Wellens syndrome

Either the positive-negative biphasic T waves of the type shown in Figure 1D or the deeply inverted (≥ 5 mm) T waves that often follow them, when occurring in the precordial leads V₂ and V₃, with or without similar changes in V₁, V₄, and V₅, are nearly pathognomonic of very recent severe ischemia or injury in the distribution of the left anterior descending artery and characterize what is known as Wellens syndrome (Figure 4).^10–13

Wellens and his colleagues showed that 75% of patients who developed these T-wave abnormalities and who were treated medically without angiographic investigation went on to develop extensive anterior wall myocardial infarction within a mean of 8.5 days.¹⁰

In a later investigation of 1,260 patients presenting with unstable angina, 180 patients (14%) had this characteristic T-wave pattern.¹¹ All of the latter patients had stenosis of 50% or more in the proximal left anterior descending artery, and 18% had total occlusion of the left anterior descending artery.

Thus, although medical management may provide symptomatic improvement at first, early coronary angiography and revascularization should be strongly considered in anyone with Wellens syndrome because it usually predicts impending anterior myocardial infarction.

Wellens syndrome is characterized by two patterns of T-wave changes. In 75% of cases, T waves are deeply (≥ 5 mm) and symmetrically inverted in leads V₂ through V₄ (Figures 1E, 4B). In 25% of cases, the T wave has a characteristic positive-negative biphasic morphology in leads V₂ through V₄ (Figures 1D, 4A).¹⁰ In both patterns, the ST segment is isoelectric or minimally elevated (< 1 mm) with a straight or convex morphology, the down-slope of the T wave is sharp, and the QT interval is often prolonged. These abnormalities are characteristically seen hours to days after the ischemic chest pain resolves. In fact, the ischemic episode is usually associated with transient ST-segment elevation or depression that progresses to the T-wave abnormality after the pain subsides.¹¹

In Wellens’ original description, only 12% of patients had increases in their creatine kinase levels, and these were small. Therefore, the electrocardiogram may be the only indication of an impending large anterior infarction in a chest-pain-free patient.¹²

T waves that are symmetrically but less deeply inverted than Wellens-type T waves may still represent ischemia. However, this finding is less specific for ischemia and is associated with better outcomes than Wellens syndrome or ST-segment deviation, particularly when the T wave is less than 3 mm deep.¹⁴ In fact, one prospective cohort study found that isolated mild T-wave inversion in patients presenting with acute coronary syndrome is associated with a favorable long-term outcome, similar to that in patients with no electrocardiographic changes.¹⁵

FREQUENTLY MISSED DIAGNOSES MANIFESTING AS ST-SEGMENT DEPRESSION OR T-WAVE INVERSION

True posterior ST-segment elevation myocardial infarction

When accompanied by inferior STEMI, posterior infarction is easily recognized, but it can be difficult to diagnose when it occurs alone, the so-called true posterior STEMI.

ST-segment depression that is most prominent in leads V₁ through V₃ often indicates posterior STEMI rather than non–ST-segment elevation ischemia and indicates the need for emergency revascularization. In fact, in the setting of posterior infarction, leads V₁, V₂, and V₃ predominate as the areas of maximum depression, whereas greater ST-segment depression in the lateral precordial leads (V₄, V₅, and V₆) or inferior leads (II, III, and aVF) is more indicative of nonocclusive and nonregional subendocardial ischemia (Figure 5).^8,16–18

In most cases of posterior infarction, the posterior chest leads V₇, V₈, and V₉ reveal ST-segment elevation.¹⁹ One study found that ST-segment depression in the anterior precordial leads was as sensitive as ST-segment elevation in leads V₇ through V₉ in identifying posterior myocardial infarction (sensitivity 80%),²⁰ while other studies found that ST-segment deviation on standard 12-lead electrocardiography has a lower sensitivity (about 60%) in identifying posterior infarction.^18,21

Tall or wide (≥ 0.04-s) R waves in leads V₁ or V₂, particularly when associated with upright T waves, suggest posterior infarction and may further corroborate this diagnosis, but this finding may take up to 24 hours to manifest and is seen in only about 50% of patients with posterior infarction.²¹

Studies have shown that ST-segment elevation on standard 12-lead electrocardiography is found in fewer than 50% of patients with acute left circumflex occlusion and inferoposterior infarction,¹⁸ yet these are cases of “missed” STEMI that indeed benefit from emergency angiography and reperfusion. In addition, studies of non–ST-segment elevation acute coronary syndrome consistently identify patients who have epicardial vessel occlusion (about 15%–20% of cases),¹⁸ yet their initial angiography is usually delayed for hours or days after the initial presentation.

A subgroup analysis from TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction 38) evaluated patients with isolated anterior ST-segment depression. An occluded “culprit” artery was found 26% of the time, most often the left circumflex artery. Moreover, those patients had a significantly higher rate of death or myocardial infarction at 30-day follow-up than patients without a culprit artery, probably related to delayed revascularization.²²

Recognizing that ST-segment depression that is greatest in leads V₁, V₂, or V₃ represents posterior infarction helps identify a portion of the missed STEMIs in a timely fashion. In addition, in cases of anterior ST-segment depression and in cases of chest pain with nondiagnostic electrocardiography, the recording of ST elevation in leads V₇, V₈, and V₉ is highly sensitive for detecting a true posterior injury.

 

 

Acute pulmonary embolism

An anterior ischemic pattern of symmetric T-wave inversion in the precordial leads V₁ through V₄ may also be a sign of acute or chronic right ventricular strain, particularly acute pulmonary embolism. Sinus tachycardia is usually present, but other signs of pulmonary embolism, such as right ventricular hypertrophy and right bundle branch block, may be absent. In fact, T-wave inversion in leads V₁ through V₄ is noted in 19% of patients with nonmassive pulmonary embolism and in 85% of patients with massive pulmonary embolism, and is the most sensitive and specific electrocardiographic finding in massive pulmonary embolism.²³

In addition, acute pulmonary embolism may be associated with T-wave inversion in leads III and aVF,²⁴ and changes of concomitant anterior and inferior ischemia should always raise the question of this diagnosis.

In one retrospective study of patients with acute pulmonary embolism, nonspecific ST-segment or T-wave changes were the most common finding on electrocardiography, noted in 49%.²⁵ Rapid regression of these changes on serial tracings favors pulmonary embolism rather than myocardial infarction.

ST-segment depression reciprocal to a subtle ST-segment elevation

When ST-segment elevation occurs in two contiguous standard leads while ST-segment depression occurs in other leads, and when the ST-segment and T-wave abnormalities are ischemic rather than secondary to depolarization abnormalities, ST-segment elevation is considered the primary ischemic abnormality whereas ST-segment depression is often considered a reciprocal “mirror image” change. This “reciprocal” change may also represent remote ischemia in a distant territory in patients with multivessel coronary disease.^26,27

Reciprocal ST-segment depression is present in all patients with inferior myocardial infarction and in 70% of patients with anterior myocardial infarction.²⁸

However, it is important to recognize that the magnitude of ST-segment elevation and reciprocal ST-segment depression is affected by the distance of the leads recording these changes from the ischemic region and their angle of deviation from the ischemic region.²⁹ This explains why occasionally—and particularly when the overall amplitude of the QRS complex is low—the magnitude of ST-segment elevation is small, whereas the reciprocal ST-segment depression is more prominent. In fact, in the absence of left ventricular hypertrophy or left bundle branch block, the reciprocal ST-segment depression should be sought. It is of great utility in patients with acute cardiac symptoms and mild elevation of ST segments of 1 to 1.5 mm in two contiguous leads, as it strongly suggests the diagnosis of STEMI rather than other causes of mild ST-segment elevation (1–1.5 mm) (Figure 6).³⁰ The less-pronounced ST-segment elevation is often overlooked, and the patient is erroneously diagnosed with non–ST-segment elevation acute coronary syndrome rather than STEMI. This has a marked impact on patient management, as STEMI requires emergency revascularization, while non–ST-segment elevation ischemia requires early (but not emergency) coronary angiography.

Hypokalemia and digitalis effect

ST-segment depression, T-wave flattening, and prominent U waves are the hallmarks of hypokalemia and can be mistaken for ischemic changes, including ischemic lengthening of the QT interval (Figure 7).^31–34 Digitalis also produces ST-segment depression, low or inverted T waves, and prominent U waves, but the U waves rarely are of the giant variety seen with severe hypokalemia, and the ST-segment depression has a sagging shape. In addition, digitalis shortens the QT interval.

DIFFUSE (GLOBAL) T-WAVE INVERSION

Reproduced with permission from Glancy DL, et al. Global T-wave inversion in a 77-year-old woman. Proc (Bayl Univ Med Cent) 2009; 22:81–82.

This term is applied when the T wave is inverted in most of the standard leads except aVR, which shows a reciprocal upright T wave. The QT interval is often prolonged, and T-wave inversion is often symmetric and “giant” (> 10 mm) (Figure 8).^1,35

Walder and Spodick³⁶ have found this pattern to be caused most often by myocardial ischemia or neurologic events, particularly intracranial hemorrhage, and it seems more prevalent in women. Other causes include hypertrophic cardiomyopathy, stress-induced cardiomyopathy (takotsubo cardiomyopathy), cocaine abuse, pericarditis, pulmonary embolism, and advanced or complete atrioventricular block.^36,37

The prognosis in patients with global T-wave inversion is determined by the underlying disease, and the striking T-wave changes per se do not imply a poor prognosis.³⁸

Of note, takotsubo cardiomyopathy is characterized by electrocardiographic changes that mimic ischemia, especially STEMI, and is often impossible to differentiate from myocardial ischemia related to a coronary event without performing coronary arteriography. The most common abnormality on the admission electrocardiogram is ST-segment elevation (present in 46%–100% of patients), typically seen in the precordial leads. Within 48 hours of presentation, almost all patients also develop postischemic diffuse T-wave inversion and prolongation of the QT interval. New Q waves may be seen in 6% to 31% of patients and are usually transient.^39,40

OTHER CAUSES OF T-WAVE INVERSION OR ST-SEGMENT DEPRESSION

Various other entities may cause T-wave inversion, notably acute pericarditis or myocarditis, ^41,42 memory T-wave phenomenon,^43,44 and normal variants of repolarization (Table 1, Figure 9).⁴⁵ Additionally, a nonpathologic junctional ST-segment depression may be seen in tachycardia (Figure 10).

Depression of the ST segment and inversion of the T wave are common electrocardiographic abnormalities. Knowing the various ischemic and nonischemic morphologic features is critical for a timely diagnosis of high-risk myocardial ischemia and electrolyte- or drug-related abnormalities. Moreover, it is important to recognize that true posterior infarction or subtle ST-segment elevation infarction may masquerade as ST-segment depression ischemia, and that pulmonary embolism may masquerade as anterior ischemia. These common electrocardiographic abnormalities are summarized in Table 1.

THE ST SEGMENT AND THE T WAVE: A PRIMER

Abnormalities of the ST segment and the T wave represent abnormalities of ventricular repolarization.

The ST segment corresponds to the plateau phase of ventricular repolarization (phase 2 of the action potential), while the T wave corresponds to the phase of rapid ventricular repolarization (phase 3). ST-segment or T-wave changes may be secondary to abnormalities of depolarization, ie, pre-excitation or abnormalities of QRS voltage or duration.

On the other hand, ST-segment and T-wave abnormalities may be unrelated to any QRS abnormality, in which case they are called primary repolarization abnormalities. These are caused by ischemia, pericarditis, myocarditis, drugs (digoxin, antiarrhythmic drugs), and electrolyte abnormalities, particularly potassium abnormalities.

ST-segment deviation is usually measured at its junction with the end of the QRS complex, ie, the J point, and is referenced against the TP or PR segment.¹ But some prefer to measure the magnitude of the ST-segment deviation 40 to 80 ms after the J point, when all myocardial fibers are expected to have reached the same level of membrane potential and to form an isoelectric ST segment; at the very onset of repolarization, small differences in membrane potential may normally be seen and may cause deviation of the J point and of the early portion of the ST segment.²

Although a diagnosis of ST-segment elevation myocardial infarction (STEMI) that mandates emergency reperfusion therapy requires ST-segment elevation greater than 1 mm in at least two contiguous leads,³ any ST-segment depression or elevation (≥ 0.5 mm, using the usual standard of 1.0 mV = 10 mm) may be abnormal, particularly when the clinical context or the shape of the ST segment suggests ischemia, or when other ischemic signs such as T-wave abnormalities, Q waves, or reciprocal ST-segment changes are concomitantly present. On the other hand, ST-segment depression of up to 0.5 mm in leads V₂ and V₃ and 1 mm in the other leads may be normal.¹

In adults, the T wave normally is inverted in lead aVR; is upright or inverted in leads aVL, III, and V₁; and is upright in leads I, II, aVF, and V₂ through V₆. The T wave is considered inverted when it is deeper than 1 mm; it is considered flat when its peak amplitude is between 1.0 mm and −1.0 mm.¹

As we will discuss, certain features allow the various causes of ST-segment and T-wave abnormalities to be distinguished from one another.

SECONDARY ST-SEGMENT AND T-WAVE ABNORMALITIES

Modified with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrubhill Press; 2009:328–354.

In secondary ST-segment or T-wave abnormalities, QRS criteria for left or right ventricular hypertrophy or left or right bundle branch block or pre-excitation are usually present, and the ST segment and T wave have all of the following morphologic features (Figure 1A):

• The ST segment and T wave are directed opposite to the QRS: this is called discordance between the QRS complex and the ST-T abnormalities. In the case of right bundle branch block, the ST and T are directed opposite to the terminal portion of the QRS, ie, the part of the QRS deformed by the conduction abnormality.
• The ST segment and T wave are both abnormal and deviate in the same direction, ie, the ST segment is down-sloping and the T wave is inverted in leads with an upright QRS complex, which gives the ST-T complex a “reverse checkmark” asymmetric morphology.
• The ST and T abnormalities are not dynamic, ie, they do not change in the course of several hours to several days.

Thus, in cases of left ventricular hypertrophy or left bundle branch block, since the QRS complex is upright in the left lateral leads I, aVL, V₅, and V₆, the ST segment is characteristically depressed and the T wave is inverted in these leads (Figure 2). In cases of right ventricular hypertrophy or right bundle branch block, T waves are characteristically inverted in the right precordial leads V₁, V₂, and V₃.

Left bundle branch block is always associated with secondary ST-T abnormalities, the absence of which suggests associated ischemia. Left and right ventricular hypertrophy, on the other hand, are not always associated with ST-T abnormalities, but when these are present, they correlate with more severe hypertrophy or ventricular systolic dysfunction,⁴ and have been called strain pattern. In addition, while these morphologic features are consistent with secondary abnormalities, they do not rule out ischemia in a patient with angina.

Some exceptions to these typical morphologic features:

• Right ventricular hypertrophy and right bundle branch block may be associated with isolated T-wave inversion without ST-segment depression in precordial leads V₁, V₂, and V₃.
• Left ventricular hypertrophy may be associated with symmetric T-wave inversion without ST-segment depression or with a horizontally depressed ST segment. This may be the case in up to one-third of ST-T abnormalities secondary to left ventricular hypertrophy and is seen in hypertrophic cardiomyopathy, particularly the apical variant, in leads V₃ through V₆.⁵

 

ISCHEMIC ST-SEGMENT DEPRESSION, T-WAVE INVERSION, OR BOTH

ST-segment depression or T-wave inversion is consistent with ischemia if any of the following is true:

• The ST-segment depression or T-wave inversion is directed in the same direction as the QRS complex: this is called concordance between the QRS complex and the ST or T abnormality (Figure 1B).
• The ST segment is depressed but the T wave is upright (Figure 1C).
• The T wave has a positive-negative biphasic pattern (Figure 1D).
• The T wave is symmetrically inverted and has a pointed configuration, while the ST segment is not deviated or is upwardly bowed (coved) or horizontally depressed (Figure 1E).
• The magnitude of ST-segment depression progresses or regresses on serial tracings, or ST-segment depression progresses to T-wave abnormality during ischemia-free intervals (dynamic ST-segment depression).

Unlike ST-segment elevation, ST-segment depression does not localize ischemia.⁶ However, the extent and the magnitude of ST-segment depression correlate with the extent and the severity of ischemia. In fact, ST-segment depression in eight or more leads, combined with ST-segment elevation in leads aVR and V₁ and occurring during ischemic pain, is associated with a 75% predictive accuracy for left main coronary artery or three-vessel disease (Figure 3).^7,8 This finding may also be seen in cases of tight proximal stenosis of the left anterior descending coronary artery.⁹

Wellens syndrome

Either the positive-negative biphasic T waves of the type shown in Figure 1D or the deeply inverted (≥ 5 mm) T waves that often follow them, when occurring in the precordial leads V₂ and V₃, with or without similar changes in V₁, V₄, and V₅, are nearly pathognomonic of very recent severe ischemia or injury in the distribution of the left anterior descending artery and characterize what is known as Wellens syndrome (Figure 4).^10–13

Wellens and his colleagues showed that 75% of patients who developed these T-wave abnormalities and who were treated medically without angiographic investigation went on to develop extensive anterior wall myocardial infarction within a mean of 8.5 days.¹⁰

In a later investigation of 1,260 patients presenting with unstable angina, 180 patients (14%) had this characteristic T-wave pattern.¹¹ All of the latter patients had stenosis of 50% or more in the proximal left anterior descending artery, and 18% had total occlusion of the left anterior descending artery.

Thus, although medical management may provide symptomatic improvement at first, early coronary angiography and revascularization should be strongly considered in anyone with Wellens syndrome because it usually predicts impending anterior myocardial infarction.

Wellens syndrome is characterized by two patterns of T-wave changes. In 75% of cases, T waves are deeply (≥ 5 mm) and symmetrically inverted in leads V₂ through V₄ (Figures 1E, 4B). In 25% of cases, the T wave has a characteristic positive-negative biphasic morphology in leads V₂ through V₄ (Figures 1D, 4A).¹⁰ In both patterns, the ST segment is isoelectric or minimally elevated (< 1 mm) with a straight or convex morphology, the down-slope of the T wave is sharp, and the QT interval is often prolonged. These abnormalities are characteristically seen hours to days after the ischemic chest pain resolves. In fact, the ischemic episode is usually associated with transient ST-segment elevation or depression that progresses to the T-wave abnormality after the pain subsides.¹¹

In Wellens’ original description, only 12% of patients had increases in their creatine kinase levels, and these were small. Therefore, the electrocardiogram may be the only indication of an impending large anterior infarction in a chest-pain-free patient.¹²

T waves that are symmetrically but less deeply inverted than Wellens-type T waves may still represent ischemia. However, this finding is less specific for ischemia and is associated with better outcomes than Wellens syndrome or ST-segment deviation, particularly when the T wave is less than 3 mm deep.¹⁴ In fact, one prospective cohort study found that isolated mild T-wave inversion in patients presenting with acute coronary syndrome is associated with a favorable long-term outcome, similar to that in patients with no electrocardiographic changes.¹⁵

FREQUENTLY MISSED DIAGNOSES MANIFESTING AS ST-SEGMENT DEPRESSION OR T-WAVE INVERSION

True posterior ST-segment elevation myocardial infarction

When accompanied by inferior STEMI, posterior infarction is easily recognized, but it can be difficult to diagnose when it occurs alone, the so-called true posterior STEMI.

ST-segment depression that is most prominent in leads V₁ through V₃ often indicates posterior STEMI rather than non–ST-segment elevation ischemia and indicates the need for emergency revascularization. In fact, in the setting of posterior infarction, leads V₁, V₂, and V₃ predominate as the areas of maximum depression, whereas greater ST-segment depression in the lateral precordial leads (V₄, V₅, and V₆) or inferior leads (II, III, and aVF) is more indicative of nonocclusive and nonregional subendocardial ischemia (Figure 5).^8,16–18

In most cases of posterior infarction, the posterior chest leads V₇, V₈, and V₉ reveal ST-segment elevation.¹⁹ One study found that ST-segment depression in the anterior precordial leads was as sensitive as ST-segment elevation in leads V₇ through V₉ in identifying posterior myocardial infarction (sensitivity 80%),²⁰ while other studies found that ST-segment deviation on standard 12-lead electrocardiography has a lower sensitivity (about 60%) in identifying posterior infarction.^18,21

Tall or wide (≥ 0.04-s) R waves in leads V₁ or V₂, particularly when associated with upright T waves, suggest posterior infarction and may further corroborate this diagnosis, but this finding may take up to 24 hours to manifest and is seen in only about 50% of patients with posterior infarction.²¹

Studies have shown that ST-segment elevation on standard 12-lead electrocardiography is found in fewer than 50% of patients with acute left circumflex occlusion and inferoposterior infarction,¹⁸ yet these are cases of “missed” STEMI that indeed benefit from emergency angiography and reperfusion. In addition, studies of non–ST-segment elevation acute coronary syndrome consistently identify patients who have epicardial vessel occlusion (about 15%–20% of cases),¹⁸ yet their initial angiography is usually delayed for hours or days after the initial presentation.

A subgroup analysis from TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction 38) evaluated patients with isolated anterior ST-segment depression. An occluded “culprit” artery was found 26% of the time, most often the left circumflex artery. Moreover, those patients had a significantly higher rate of death or myocardial infarction at 30-day follow-up than patients without a culprit artery, probably related to delayed revascularization.²²

Recognizing that ST-segment depression that is greatest in leads V₁, V₂, or V₃ represents posterior infarction helps identify a portion of the missed STEMIs in a timely fashion. In addition, in cases of anterior ST-segment depression and in cases of chest pain with nondiagnostic electrocardiography, the recording of ST elevation in leads V₇, V₈, and V₉ is highly sensitive for detecting a true posterior injury.

 

 

Acute pulmonary embolism

An anterior ischemic pattern of symmetric T-wave inversion in the precordial leads V₁ through V₄ may also be a sign of acute or chronic right ventricular strain, particularly acute pulmonary embolism. Sinus tachycardia is usually present, but other signs of pulmonary embolism, such as right ventricular hypertrophy and right bundle branch block, may be absent. In fact, T-wave inversion in leads V₁ through V₄ is noted in 19% of patients with nonmassive pulmonary embolism and in 85% of patients with massive pulmonary embolism, and is the most sensitive and specific electrocardiographic finding in massive pulmonary embolism.²³

In addition, acute pulmonary embolism may be associated with T-wave inversion in leads III and aVF,²⁴ and changes of concomitant anterior and inferior ischemia should always raise the question of this diagnosis.

In one retrospective study of patients with acute pulmonary embolism, nonspecific ST-segment or T-wave changes were the most common finding on electrocardiography, noted in 49%.²⁵ Rapid regression of these changes on serial tracings favors pulmonary embolism rather than myocardial infarction.

ST-segment depression reciprocal to a subtle ST-segment elevation

When ST-segment elevation occurs in two contiguous standard leads while ST-segment depression occurs in other leads, and when the ST-segment and T-wave abnormalities are ischemic rather than secondary to depolarization abnormalities, ST-segment elevation is considered the primary ischemic abnormality whereas ST-segment depression is often considered a reciprocal “mirror image” change. This “reciprocal” change may also represent remote ischemia in a distant territory in patients with multivessel coronary disease.^26,27

Reciprocal ST-segment depression is present in all patients with inferior myocardial infarction and in 70% of patients with anterior myocardial infarction.²⁸

However, it is important to recognize that the magnitude of ST-segment elevation and reciprocal ST-segment depression is affected by the distance of the leads recording these changes from the ischemic region and their angle of deviation from the ischemic region.²⁹ This explains why occasionally—and particularly when the overall amplitude of the QRS complex is low—the magnitude of ST-segment elevation is small, whereas the reciprocal ST-segment depression is more prominent. In fact, in the absence of left ventricular hypertrophy or left bundle branch block, the reciprocal ST-segment depression should be sought. It is of great utility in patients with acute cardiac symptoms and mild elevation of ST segments of 1 to 1.5 mm in two contiguous leads, as it strongly suggests the diagnosis of STEMI rather than other causes of mild ST-segment elevation (1–1.5 mm) (Figure 6).³⁰ The less-pronounced ST-segment elevation is often overlooked, and the patient is erroneously diagnosed with non–ST-segment elevation acute coronary syndrome rather than STEMI. This has a marked impact on patient management, as STEMI requires emergency revascularization, while non–ST-segment elevation ischemia requires early (but not emergency) coronary angiography.

Hypokalemia and digitalis effect

ST-segment depression, T-wave flattening, and prominent U waves are the hallmarks of hypokalemia and can be mistaken for ischemic changes, including ischemic lengthening of the QT interval (Figure 7).^31–34 Digitalis also produces ST-segment depression, low or inverted T waves, and prominent U waves, but the U waves rarely are of the giant variety seen with severe hypokalemia, and the ST-segment depression has a sagging shape. In addition, digitalis shortens the QT interval.

DIFFUSE (GLOBAL) T-WAVE INVERSION

Reproduced with permission from Glancy DL, et al. Global T-wave inversion in a 77-year-old woman. Proc (Bayl Univ Med Cent) 2009; 22:81–82.

This term is applied when the T wave is inverted in most of the standard leads except aVR, which shows a reciprocal upright T wave. The QT interval is often prolonged, and T-wave inversion is often symmetric and “giant” (> 10 mm) (Figure 8).^1,35

Walder and Spodick³⁶ have found this pattern to be caused most often by myocardial ischemia or neurologic events, particularly intracranial hemorrhage, and it seems more prevalent in women. Other causes include hypertrophic cardiomyopathy, stress-induced cardiomyopathy (takotsubo cardiomyopathy), cocaine abuse, pericarditis, pulmonary embolism, and advanced or complete atrioventricular block.^36,37

The prognosis in patients with global T-wave inversion is determined by the underlying disease, and the striking T-wave changes per se do not imply a poor prognosis.³⁸

Of note, takotsubo cardiomyopathy is characterized by electrocardiographic changes that mimic ischemia, especially STEMI, and is often impossible to differentiate from myocardial ischemia related to a coronary event without performing coronary arteriography. The most common abnormality on the admission electrocardiogram is ST-segment elevation (present in 46%–100% of patients), typically seen in the precordial leads. Within 48 hours of presentation, almost all patients also develop postischemic diffuse T-wave inversion and prolongation of the QT interval. New Q waves may be seen in 6% to 31% of patients and are usually transient.^39,40

OTHER CAUSES OF T-WAVE INVERSION OR ST-SEGMENT DEPRESSION

Various other entities may cause T-wave inversion, notably acute pericarditis or myocarditis, ^41,42 memory T-wave phenomenon,^43,44 and normal variants of repolarization (Table 1, Figure 9).⁴⁵ Additionally, a nonpathologic junctional ST-segment depression may be seen in tachycardia (Figure 10).