Clinical Review & Education
Challenges in Clinical Electrocardiography
Takotsubo Cardiomyopathy How T Waves Behave Under Stress Arjun Sinha, MD, MS; Jasmine Rassiwala, MD, MPH; Nora Goldschlager, MD
lack of evidence of significant coronary artery disease that could explain the patient’s wall motion abnormalities or clinical presentation, she was diagnosed with stress cardiomyopathy (Takotsubo cardiomyopathy). Further history revealed that the patient’s son had been diagnosed with terminal cancer and had been enrolled in hospice care 3 months prior to presentation. Our patient was the primary caregiver and had been having increasing episodes of chest pain as her son’s condition deteriorated. She began medical treatment that included metoprolol succinate and lisinopril for her chest pain and left ventricular wall motion abnormalities. A repeated TTE performed 3 months after presentation showed complete resolution of the wall motion abnormalities.
A woman in her 60s with hypertension and hyperlipidemia presented with chest pain for 3 days. She denied any cardiac history but reported intermittent substernal chest pain for the past few months that had worsened in the past week. She denied associated symptoms. Her vital signs and cardiopulmonary examination results were within normal limits; her baseline electrocardiogram (ECG) is shown in Figure 1. Initial troponin level was 0.33 μg/L. Her chest pain resolved after administration of sublingual nitroglycerin, and her troponin level decreased to 0.1 μg/L. Given the patient’s elevated cardiac enzymes, she was admitted for treatment of non-ST elevation myocardial infarction. Twelve hours after admission, the patient had another episode of substernal chest pain with troponin elevation to 0.3 μg/L. An ECG recorded at that time is shown in Figure 2. She was treated with nitrates, and her chest pain resolved. Another ECG was obtained after her pain resolved and her subsequent troponin measurements trended down (Figure 3). Question: What finding does this series of ECGs suggest?
Discussion The ECG on presentation (Figure 1) shows symmetric T-wave inversions (TWIs) in all precordial leads (V1-V6); patient had no prior ECG. While TWIs are associated with many conditions, from normal variant to cerebrovascular accident and pericarditis, given the patient’s clinical history, there was concern for myocardial ischemia. The second ECG (Figure 2), recorded during the patient’s anginal episode, is notable for ventricular bigeminy and normalization of the T waves in the sinus-stimulated QRS complexes in the precordial leads (V1-V6). The third ECG (Figure 3), obtained after resolution of chest pain, shows reversion to the symmetric T-wave inversions in all pre-
Clinical Course A transthoracic echocardiogram (TTE) was obtained, which showed akinesis of the left ventricular apex and severe hypokinesis of the apical anterior and anteroseptal walls, with relative basal hyperkinesis and preserved overall left ventricular ejection fraction. The patient underwent coronary angiography, which revealed only mild nonobstructive coronary artery disease and no vasospasm. Given
Figure 1. Initial Electrocardiogram on Presentation I
aVT
V1
V4
II
aVL
V2
V5
III
aVT
V3
V6
II
842
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Challenges in Clinical Electrocardiography Clinical Review & Education
Figure 2. Second Electrocardiogram in the Setting of Substernal Chest Pain I
aVT
V1
V4
II
aVL
V2
V5
III
aVT
V3
V6
II
Figure 3. Third Electrocardiogram Following Resolution of Chest Pain I
aVT
V1
V4
II
aVL
V2
V5
III
aVT
V3
V6
II
cordial leads (V1-V6). The change from the abnormal inverted T waves to more normal-appearing upright T waves, followed by return to baseline T-wave inversions as the anginal symptoms resolve, is defined as T-wave pseudonormalization. Given the presence of premature ventricular contractions (PVCs) in the second ECG, cardiac memory was considered as an explanation for this patient’s T-wave changes. Cardiac memory is a phenomenon in which the T-wave axis of a normal sinus beat following an abnormal ventricular depolarization is concordant with the QRS complex of that preceding abnormal depolarization.1 However, in the present case, the T-wave axis of the normal sinus beats and the QRS axis of the preceding PVCs are concordant only in precordial leads V1-V2 (Figure 2). jamainternalmedicine.com
Thus, the more diffuse ECG findings in Figure 2 are more likely representative of T-wave pseudonormalization than cardiac or T-wave memory. T-wave pseudonormalization is known to be associated with myocardial ischemia.2 Initial studies showed that patients with inverted T waves at baseline develop pseudonormalization in response to either spontaneous or provoked angina.2 On coronary angiography, all described patients had a greater than 75% occlusion of the corresponding coronary artery.2 The cellular and electrophysiological mechanism underlying pseudonormalization is unclear. However, it is generally thought that T-wave pseudonormalization is due to a new ischemic event causing shortening of the action potential (Reprinted) JAMA Internal Medicine May 2015 Volume 175, Number 5
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Leeds User on 05/17/2015
843
Clinical Review & Education Challenges in Clinical Electrocardiography
duration in myocardial cells with chronic ischemic injury.3 A more recent prospective study showed that the incidence of pseudonormalization in patients presenting with plaque rupture is 1%.4 All patients in this study had severely narrowed or totally occluded coronary arteries that corresponded to the related ischemic changes on the ECG.4 While precordial T-wave inversion and ST-segment elevation often indicate anterior myocardial infarction due to acute coronary disease, they are also the 2 most common ECG findings in patients with stress cardiomyopathy.5 Stress cardiomyopathy ECG manifestations have been separated into 4 stages: (1) ST segment elevation after symptom onset; (2) initial T-wave inversion after resolution of ST segment elevation during days 1 to 3; (3) transient improvement in T-wave inversions; and (4) deeper T-wave inversions that can last up to months.5 T-wave pseudonormalization has not been previously described in a patient with stress cardiomyopathy. The presARTICLE INFORMATION Author Affiliations: Department of Internal Medicine, University of California, San Francisco (Sinha, Rassiwala); Division of Cardiology, Department of Internal Medicine, San Francisco General Hospital, San Francisco, California (Goldschlager). Corresponding Author: Arjun Sinha, MD, MS, Department of Internal Medicine, University of California, San Francisco, 1343 32nd Ave, San Francisco, CA 94122 ([email protected]). Section Editors: Jeffrey Tabas, MD; Gregory M. Marcus, MD; Nora Goldschlager, MD; Elsayed Z. Soliman, MD, MSc, MS.
844
ent case shows that T-wave pseudonormalization can occur in patients without coronary artery disease.
Take-Home Points • T-wave inversions are related to many disease states, but with respect to coronary artery disease, they may result from subendocardial ischemia, acute coronary syndrome, or past myocardial infarctions. • T-wave pseudonormalization is most often a sign of acute myocardial ischemia, and serial ECGs can be useful in detecting this phenomenon. However, as seen in this case, T-wave pseudonormalization can occur in patients without coronary artery disease. • Precordial T-wave inversions and ST-segment elevations are the most common ECG findings in stress cardiomyopathy, and thus these patients are often initially diagnosed as having ST-segment elevation myocardial infarction and taken for emergent catheterization.
Published Online: March 9, 2015. doi:10.1001/jamainternmed.2015.52. Conflict of Interest Disclosures: None reported.
sation of the T wave: old wine? a fresh look at a 25-year-old observation. Neth Heart J. 2007; 15(7-8):257-259.
1. Rosen MR, Cohen IS. Cardiac memory ... new insights into molecular mechanisms. J Physiol. 2006;570(pt 2):209-218.
4. Ulucan C, Yavuzgil O, Kayikçioğlu M, et al. Pseudonormalization: clinical, electrocardiographic, echocardiographic, and angiographic characteristics. Anadolu Kardiyol Derg. 2007;7(suppl 1):175-177.
2. Noble RJ, Rothbaum DA, Knoebel SB, McHenry PL, Anderson GJ. Normalization of abnormal T waves in ischemia. Arch Intern Med. 1976;136(4): 391-395.
5. Kosuge M, Kimura K. Electrocardiographic findings of Takotsubo cardiomyopathy as compared with those of anterior acute myocardial infarction. J Electrocardiol. 2014;47(5):684-689.
REFERENCES
3. Simons A, Robins LJH, Hooghoudt TEH, Meursing BT, Oude Ophuis AJ. Pseudonormali-
JAMA Internal Medicine May 2015 Volume 175, Number 5 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Leeds User on 05/17/2015
jamainternalmedicine.com
Challenges in Clinical Electrocardiography
Takotsubo Cardiomyopathy How T Waves Behave Under Stress Arjun Sinha, MD, MS; Jasmine Rassiwala, MD, MPH; Nora Goldschlager, MD
lack of evidence of significant coronary artery disease that could explain the patient’s wall motion abnormalities or clinical presentation, she was diagnosed with stress cardiomyopathy (Takotsubo cardiomyopathy). Further history revealed that the patient’s son had been diagnosed with terminal cancer and had been enrolled in hospice care 3 months prior to presentation. Our patient was the primary caregiver and had been having increasing episodes of chest pain as her son’s condition deteriorated. She began medical treatment that included metoprolol succinate and lisinopril for her chest pain and left ventricular wall motion abnormalities. A repeated TTE performed 3 months after presentation showed complete resolution of the wall motion abnormalities.
A woman in her 60s with hypertension and hyperlipidemia presented with chest pain for 3 days. She denied any cardiac history but reported intermittent substernal chest pain for the past few months that had worsened in the past week. She denied associated symptoms. Her vital signs and cardiopulmonary examination results were within normal limits; her baseline electrocardiogram (ECG) is shown in Figure 1. Initial troponin level was 0.33 μg/L. Her chest pain resolved after administration of sublingual nitroglycerin, and her troponin level decreased to 0.1 μg/L. Given the patient’s elevated cardiac enzymes, she was admitted for treatment of non-ST elevation myocardial infarction. Twelve hours after admission, the patient had another episode of substernal chest pain with troponin elevation to 0.3 μg/L. An ECG recorded at that time is shown in Figure 2. She was treated with nitrates, and her chest pain resolved. Another ECG was obtained after her pain resolved and her subsequent troponin measurements trended down (Figure 3). Question: What finding does this series of ECGs suggest?
Discussion The ECG on presentation (Figure 1) shows symmetric T-wave inversions (TWIs) in all precordial leads (V1-V6); patient had no prior ECG. While TWIs are associated with many conditions, from normal variant to cerebrovascular accident and pericarditis, given the patient’s clinical history, there was concern for myocardial ischemia. The second ECG (Figure 2), recorded during the patient’s anginal episode, is notable for ventricular bigeminy and normalization of the T waves in the sinus-stimulated QRS complexes in the precordial leads (V1-V6). The third ECG (Figure 3), obtained after resolution of chest pain, shows reversion to the symmetric T-wave inversions in all pre-
Clinical Course A transthoracic echocardiogram (TTE) was obtained, which showed akinesis of the left ventricular apex and severe hypokinesis of the apical anterior and anteroseptal walls, with relative basal hyperkinesis and preserved overall left ventricular ejection fraction. The patient underwent coronary angiography, which revealed only mild nonobstructive coronary artery disease and no vasospasm. Given
Figure 1. Initial Electrocardiogram on Presentation I
aVT
V1
V4
II
aVL
V2
V5
III
aVT
V3
V6
II
842
JAMA Internal Medicine May 2015 Volume 175, Number 5 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Leeds User on 05/17/2015
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Challenges in Clinical Electrocardiography Clinical Review & Education
Figure 2. Second Electrocardiogram in the Setting of Substernal Chest Pain I
aVT
V1
V4
II
aVL
V2
V5
III
aVT
V3
V6
II
Figure 3. Third Electrocardiogram Following Resolution of Chest Pain I
aVT
V1
V4
II
aVL
V2
V5
III
aVT
V3
V6
II
cordial leads (V1-V6). The change from the abnormal inverted T waves to more normal-appearing upright T waves, followed by return to baseline T-wave inversions as the anginal symptoms resolve, is defined as T-wave pseudonormalization. Given the presence of premature ventricular contractions (PVCs) in the second ECG, cardiac memory was considered as an explanation for this patient’s T-wave changes. Cardiac memory is a phenomenon in which the T-wave axis of a normal sinus beat following an abnormal ventricular depolarization is concordant with the QRS complex of that preceding abnormal depolarization.1 However, in the present case, the T-wave axis of the normal sinus beats and the QRS axis of the preceding PVCs are concordant only in precordial leads V1-V2 (Figure 2). jamainternalmedicine.com
Thus, the more diffuse ECG findings in Figure 2 are more likely representative of T-wave pseudonormalization than cardiac or T-wave memory. T-wave pseudonormalization is known to be associated with myocardial ischemia.2 Initial studies showed that patients with inverted T waves at baseline develop pseudonormalization in response to either spontaneous or provoked angina.2 On coronary angiography, all described patients had a greater than 75% occlusion of the corresponding coronary artery.2 The cellular and electrophysiological mechanism underlying pseudonormalization is unclear. However, it is generally thought that T-wave pseudonormalization is due to a new ischemic event causing shortening of the action potential (Reprinted) JAMA Internal Medicine May 2015 Volume 175, Number 5
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Leeds User on 05/17/2015
843
Clinical Review & Education Challenges in Clinical Electrocardiography
duration in myocardial cells with chronic ischemic injury.3 A more recent prospective study showed that the incidence of pseudonormalization in patients presenting with plaque rupture is 1%.4 All patients in this study had severely narrowed or totally occluded coronary arteries that corresponded to the related ischemic changes on the ECG.4 While precordial T-wave inversion and ST-segment elevation often indicate anterior myocardial infarction due to acute coronary disease, they are also the 2 most common ECG findings in patients with stress cardiomyopathy.5 Stress cardiomyopathy ECG manifestations have been separated into 4 stages: (1) ST segment elevation after symptom onset; (2) initial T-wave inversion after resolution of ST segment elevation during days 1 to 3; (3) transient improvement in T-wave inversions; and (4) deeper T-wave inversions that can last up to months.5 T-wave pseudonormalization has not been previously described in a patient with stress cardiomyopathy. The presARTICLE INFORMATION Author Affiliations: Department of Internal Medicine, University of California, San Francisco (Sinha, Rassiwala); Division of Cardiology, Department of Internal Medicine, San Francisco General Hospital, San Francisco, California (Goldschlager). Corresponding Author: Arjun Sinha, MD, MS, Department of Internal Medicine, University of California, San Francisco, 1343 32nd Ave, San Francisco, CA 94122 ([email protected]). Section Editors: Jeffrey Tabas, MD; Gregory M. Marcus, MD; Nora Goldschlager, MD; Elsayed Z. Soliman, MD, MSc, MS.
844
ent case shows that T-wave pseudonormalization can occur in patients without coronary artery disease.
Take-Home Points • T-wave inversions are related to many disease states, but with respect to coronary artery disease, they may result from subendocardial ischemia, acute coronary syndrome, or past myocardial infarctions. • T-wave pseudonormalization is most often a sign of acute myocardial ischemia, and serial ECGs can be useful in detecting this phenomenon. However, as seen in this case, T-wave pseudonormalization can occur in patients without coronary artery disease. • Precordial T-wave inversions and ST-segment elevations are the most common ECG findings in stress cardiomyopathy, and thus these patients are often initially diagnosed as having ST-segment elevation myocardial infarction and taken for emergent catheterization.
Published Online: March 9, 2015. doi:10.1001/jamainternmed.2015.52. Conflict of Interest Disclosures: None reported.
sation of the T wave: old wine? a fresh look at a 25-year-old observation. Neth Heart J. 2007; 15(7-8):257-259.
1. Rosen MR, Cohen IS. Cardiac memory ... new insights into molecular mechanisms. J Physiol. 2006;570(pt 2):209-218.
4. Ulucan C, Yavuzgil O, Kayikçioğlu M, et al. Pseudonormalization: clinical, electrocardiographic, echocardiographic, and angiographic characteristics. Anadolu Kardiyol Derg. 2007;7(suppl 1):175-177.
2. Noble RJ, Rothbaum DA, Knoebel SB, McHenry PL, Anderson GJ. Normalization of abnormal T waves in ischemia. Arch Intern Med. 1976;136(4): 391-395.
5. Kosuge M, Kimura K. Electrocardiographic findings of Takotsubo cardiomyopathy as compared with those of anterior acute myocardial infarction. J Electrocardiol. 2014;47(5):684-689.
REFERENCES
3. Simons A, Robins LJH, Hooghoudt TEH, Meursing BT, Oude Ophuis AJ. Pseudonormali-
JAMA Internal Medicine May 2015 Volume 175, Number 5 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Leeds User on 05/17/2015
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