Clinical Review & Education
Challenges in Clinical Electrocardiography
Intracranial Hemorrhage and Deep T-Wave Inversions Kevin K. Manocha, MD; David Snipelisky, MD; Nandan S. Anavekar, MD
A woman in her 70s with a medical history significant for atrial fibrillation and cardioembolic stroke who was receiving long-term anticoagulation therapy with warfarin (international normalized ratio, 2.3) presented to an outside facility with sudden onset of nausea and vertigo. Her mental status declined and she was unable to protect her airway, prompting intubation. Computed tomographic scan (CT) at that time was negative for any intracranial pathologic findings. On arrival to our facility, the patient remained lethargic and unresponsive; therefore, a second noncontrast head CT was performed, which showed no evidence for cerebellar hemorrhage, edema, or other acute findings. Her initial serum troponin level was unremarkable, yet she developed a peak troponin level of 0.13 ng/mL (to convert to micrograms per liter, multiply by 1.0). Her initial electrocardiogram (ECG) showed a rhythm of atrial fibrillation without ischemic changes, yet a subsequent study 6 hours later showed new T-wave abnormalities, as represented in the Figure. Question: Based on the electrocardiographic abnormalities, what clinical diagnosis should be entertained?
Interpretation The patient’s second ECG shows atrial fibrillation at 86 beats per minute, normal axis, normal QRS length, QTc increased at 632 ms, and T-wave inversions in all limb and precordial leads, which were new compared with her prior ECG.
Clinical Course Based on the patient’s clinical deterioration and new abnormalities on her ECG, magnetic resonance imaging of the head was obtained, revealing a large acute left cerebellar hemisphere infarct with moderate petechial hemorrhage. The effects of her intravenous heparin were reversed with protamine therapy and warfarin reversed with vitamin K supplementation. Subsequent head CT showed evidence of a large posterior inferior cerebellar artery distribution infarct, mild hemorrhage, and early effacement of the fourth ventricle. A transesophageal echocardiogram was performed, and sludge was noted in her atrial appendage. Following a prolonged hospital course, the patient had restarted her warfarin therapy and was admitted to a comprehensive inpatient rehabilitation facility. Her clinical status continued to improve, and she was ultimately discharged home with 24-hour home health care support.
Discussion We present a case with global deep T-wave inversions on ECG and elevated troponin levels in a patient with acute stroke and subsequent intraparenchymal hemorrhage. Given their embolic nature, strokes due to atrial fibrillation tend to affect the large distal intracranial arteries. Most commonly, the middle cerebral artery and less commonly, the posterior cerebral artery is usually affected.1 In this case, the patient’s symptoms were not consistent with a middle cejamainternalmedicine.com
rebral or posterior cerebral artery lesion. Thus, in conjunction with her therapeutic international normalized ratio and significant ECG changes, the suspicion of major intracranial bleeding was high. Global T-wave inversions on ECG are often nonspecific but can be a sign of major neurocardiogenic injury including, but not limited to, intracranial hemorrhage, myocarditis, Takotsubo cardiomyopathy, cocaine use, and pheochromocytoma.2-4 An important finding in this case suggestive of a significant neurocardiogenic injury is the symmetry and pattern of the T-wave inversions. Although conduction abnormalities can cause T-wave inversions on ECG, the pattern is often asymmetric. An example would be a right bundle branch block, in which one should see appropriate discordance of the terminal QRS and T-wave deflections. So with an rSR′ pattern, the T wave should in fact be inverted. Furthermore, this should be only on the leads on the right side. The same appropriate discordance would be seen in a left bundle branch block on the leads on the left side only. Global or symmetric T-wave inversions, however, imply a primary disorder2 because it would affect the leads on both the right and left sides. Furthermore, there would be an absence of appropriate discordance. The mechanism via which neurocardiogenic injury causes T-wave inversions, especially given the lack of known anatomic correlation, is thought to be the result of a catecholamine-mediated stunning of the myocardium, causing global repolarization abnormalities.4,5 Therefore, in patients with other neurologic dysfunction, the finding of deep symmetric T-wave inversion should key the clinician into a possible etiology of intracranial disease. In addition to the ECG changes, the accompanying troponin level elevation in this case is also interesting because the differential diagnosis for troponinemia includes not only acute coronary syndrome but also renal disease, sepsis, pulmonary embolism, congestive heart failure, myocarditis and/or pericarditis, cardiac trauma, defibrillation, direct cardiotoxic effect, and, as highlighted by this case, an acute intracranial process. Mechanisms accounting for the troponinemia include inadequate urinary troponin clearance in end-stage renal disease, myocardial oxygen supplydemand mismatch in sepsis, acute right ventricular strain in pulmonary embolism, ongoing myocyte loss and fibrosis in heart failure, myocyte inflammation in myocarditis and/or pericarditis, chest trauma leading to myocardial contusion, electrical myocyte injury after defibrillation, and direct toxic effects of medication such as certain chemotherapy agents, among others. 6 This patient’s troponinemia is likely due to neurocardiogenic injury and is actually a poor prognostic marker because a troponin level greater than 0.1 ng/mL has been associated with an increased 30-day mortality.7
Take-Home Points • T-wave inversions have a broad differential diagnosis, and clinical context is of paramount importance in explaining such changes. (Reprinted) JAMA Internal Medicine Published online May 4, 2015
Copyright 2015 American Medical Association. All rights reserved.
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Clinical Review & Education Challenges in Clinical Electrocardiography
Figure. Electrocardiogram at Baseline and After Subarachnoid Hemorrhage A
I
aaV VR V R aVR
V1 V1
V4 V4
II II
aVL aVL
V2 V2
V5 V5
III
VFF V aVF
V3 V3
V6 V6
II II
V1 V1
V5 V5
B
I
aVR aV VR V R
V1 V1
III
aaV VL aVL
V2 V2
IIII II
aVF aVF VF
V3 V3
V4 V4
V5 V5
V6 V6
II
V1 V1
V5 V5
E2
JAMA Internal Medicine Published online May 4, 2015 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Thomas Jefferson University User on 05/13/2015
jamainternalmedicine.com
Challenges in Clinical Electrocardiography Clinical Review & Education
• AsymmetricT-waveinversioninfersaconductionabnormality,whereas symmetric T-wave inversions signal a primary systemic etiology. • Neurocardiogenic injury via catecholamine surge and myocardial stunning is thought to be the underlying mechanism for global T-wave inversions.
• Troponinemia can accompany T-wave inversions without intrinsic coronary disease. • In patients with neurologic complaints and/or findings and symmetric T-wave inversions, the suspicion of intracranial disease should be entertained.
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota (Manocha); Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota (Snipelisky, Anavekar).
1. Smith WS, English JD, Johnston SC. Cerebrovascular diseases. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content .aspx?bookid=331&Sectionid=40727186. Accessed March 26, 2015.
Corresponding Author: Kevin K. Manocha, MD, Department of Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (manocha.kevin @mayo.edu). Section Editors: Jeffrey Tabas, MD; Gregory M. Marcus, MD; Nora Goldschlager, MD; Elsayed Z. Soliman, MD, MSc, MS. Published Online: May 4, 2015. doi:10.1001/jamainternmed.2015.1337. Conflict of Interest Disclosures: None reported.
jamainternalmedicine.com
2. Walder LA, Spodick DH. Global T wave inversion. J Am Coll Cardiol. 1991;17(7):1479-1485. 3. Qaqa AY, Suleiman A, Alsumrain M, Debari VA, Kirmani J, Shamoon FE. Electrocardiographic abnormalities in patients presenting with intracranial parenchymal haemorrhage. Acta Cardiol. 2012;67(6):635-639.
5. Lambert G, Naredi S, Edén E, Rydenhag B, Friberg P. Sympathetic nervous activation following subarachnoid hemorrhage: influence of intravenous clonidine. Acta Anaesthesiol Scand. 2002;46(2): 160-165. 6. Mannu GS. The non-cardiac use and significance of cardiac troponins. Scott Med J. 2014;59(3):172-178. 7. Duello KM, Nagel JP, Thomas CS, Blackshear JL, Freeman WD. Relationship of troponin T and age- and sex-adjusted BNP elevation following subarachnoid hemorrhage with 30-day mortality. Neurocrit Care. 2015.
4. Wybraniec M, Mizia-Stec K, Krzych L. Stress cardiomyopathy: yet another type of neurocardiogenic injury. Cardiovasc Pathol. 2014;23 (3):113-120.
(Reprinted) JAMA Internal Medicine Published online May 4, 2015
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Thomas Jefferson University User on 05/13/2015
E3
Challenges in Clinical Electrocardiography
Intracranial Hemorrhage and Deep T-Wave Inversions Kevin K. Manocha, MD; David Snipelisky, MD; Nandan S. Anavekar, MD
A woman in her 70s with a medical history significant for atrial fibrillation and cardioembolic stroke who was receiving long-term anticoagulation therapy with warfarin (international normalized ratio, 2.3) presented to an outside facility with sudden onset of nausea and vertigo. Her mental status declined and she was unable to protect her airway, prompting intubation. Computed tomographic scan (CT) at that time was negative for any intracranial pathologic findings. On arrival to our facility, the patient remained lethargic and unresponsive; therefore, a second noncontrast head CT was performed, which showed no evidence for cerebellar hemorrhage, edema, or other acute findings. Her initial serum troponin level was unremarkable, yet she developed a peak troponin level of 0.13 ng/mL (to convert to micrograms per liter, multiply by 1.0). Her initial electrocardiogram (ECG) showed a rhythm of atrial fibrillation without ischemic changes, yet a subsequent study 6 hours later showed new T-wave abnormalities, as represented in the Figure. Question: Based on the electrocardiographic abnormalities, what clinical diagnosis should be entertained?
Interpretation The patient’s second ECG shows atrial fibrillation at 86 beats per minute, normal axis, normal QRS length, QTc increased at 632 ms, and T-wave inversions in all limb and precordial leads, which were new compared with her prior ECG.
Clinical Course Based on the patient’s clinical deterioration and new abnormalities on her ECG, magnetic resonance imaging of the head was obtained, revealing a large acute left cerebellar hemisphere infarct with moderate petechial hemorrhage. The effects of her intravenous heparin were reversed with protamine therapy and warfarin reversed with vitamin K supplementation. Subsequent head CT showed evidence of a large posterior inferior cerebellar artery distribution infarct, mild hemorrhage, and early effacement of the fourth ventricle. A transesophageal echocardiogram was performed, and sludge was noted in her atrial appendage. Following a prolonged hospital course, the patient had restarted her warfarin therapy and was admitted to a comprehensive inpatient rehabilitation facility. Her clinical status continued to improve, and she was ultimately discharged home with 24-hour home health care support.
Discussion We present a case with global deep T-wave inversions on ECG and elevated troponin levels in a patient with acute stroke and subsequent intraparenchymal hemorrhage. Given their embolic nature, strokes due to atrial fibrillation tend to affect the large distal intracranial arteries. Most commonly, the middle cerebral artery and less commonly, the posterior cerebral artery is usually affected.1 In this case, the patient’s symptoms were not consistent with a middle cejamainternalmedicine.com
rebral or posterior cerebral artery lesion. Thus, in conjunction with her therapeutic international normalized ratio and significant ECG changes, the suspicion of major intracranial bleeding was high. Global T-wave inversions on ECG are often nonspecific but can be a sign of major neurocardiogenic injury including, but not limited to, intracranial hemorrhage, myocarditis, Takotsubo cardiomyopathy, cocaine use, and pheochromocytoma.2-4 An important finding in this case suggestive of a significant neurocardiogenic injury is the symmetry and pattern of the T-wave inversions. Although conduction abnormalities can cause T-wave inversions on ECG, the pattern is often asymmetric. An example would be a right bundle branch block, in which one should see appropriate discordance of the terminal QRS and T-wave deflections. So with an rSR′ pattern, the T wave should in fact be inverted. Furthermore, this should be only on the leads on the right side. The same appropriate discordance would be seen in a left bundle branch block on the leads on the left side only. Global or symmetric T-wave inversions, however, imply a primary disorder2 because it would affect the leads on both the right and left sides. Furthermore, there would be an absence of appropriate discordance. The mechanism via which neurocardiogenic injury causes T-wave inversions, especially given the lack of known anatomic correlation, is thought to be the result of a catecholamine-mediated stunning of the myocardium, causing global repolarization abnormalities.4,5 Therefore, in patients with other neurologic dysfunction, the finding of deep symmetric T-wave inversion should key the clinician into a possible etiology of intracranial disease. In addition to the ECG changes, the accompanying troponin level elevation in this case is also interesting because the differential diagnosis for troponinemia includes not only acute coronary syndrome but also renal disease, sepsis, pulmonary embolism, congestive heart failure, myocarditis and/or pericarditis, cardiac trauma, defibrillation, direct cardiotoxic effect, and, as highlighted by this case, an acute intracranial process. Mechanisms accounting for the troponinemia include inadequate urinary troponin clearance in end-stage renal disease, myocardial oxygen supplydemand mismatch in sepsis, acute right ventricular strain in pulmonary embolism, ongoing myocyte loss and fibrosis in heart failure, myocyte inflammation in myocarditis and/or pericarditis, chest trauma leading to myocardial contusion, electrical myocyte injury after defibrillation, and direct toxic effects of medication such as certain chemotherapy agents, among others. 6 This patient’s troponinemia is likely due to neurocardiogenic injury and is actually a poor prognostic marker because a troponin level greater than 0.1 ng/mL has been associated with an increased 30-day mortality.7
Take-Home Points • T-wave inversions have a broad differential diagnosis, and clinical context is of paramount importance in explaining such changes. (Reprinted) JAMA Internal Medicine Published online May 4, 2015
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Thomas Jefferson University User on 05/13/2015
E1
Clinical Review & Education Challenges in Clinical Electrocardiography
Figure. Electrocardiogram at Baseline and After Subarachnoid Hemorrhage A
I
aaV VR V R aVR
V1 V1
V4 V4
II II
aVL aVL
V2 V2
V5 V5
III
VFF V aVF
V3 V3
V6 V6
II II
V1 V1
V5 V5
B
I
aVR aV VR V R
V1 V1
III
aaV VL aVL
V2 V2
IIII II
aVF aVF VF
V3 V3
V4 V4
V5 V5
V6 V6
II
V1 V1
V5 V5
E2
JAMA Internal Medicine Published online May 4, 2015 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Thomas Jefferson University User on 05/13/2015
jamainternalmedicine.com
Challenges in Clinical Electrocardiography Clinical Review & Education
• AsymmetricT-waveinversioninfersaconductionabnormality,whereas symmetric T-wave inversions signal a primary systemic etiology. • Neurocardiogenic injury via catecholamine surge and myocardial stunning is thought to be the underlying mechanism for global T-wave inversions.
• Troponinemia can accompany T-wave inversions without intrinsic coronary disease. • In patients with neurologic complaints and/or findings and symmetric T-wave inversions, the suspicion of intracranial disease should be entertained.
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota (Manocha); Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota (Snipelisky, Anavekar).
1. Smith WS, English JD, Johnston SC. Cerebrovascular diseases. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content .aspx?bookid=331&Sectionid=40727186. Accessed March 26, 2015.
Corresponding Author: Kevin K. Manocha, MD, Department of Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (manocha.kevin @mayo.edu). Section Editors: Jeffrey Tabas, MD; Gregory M. Marcus, MD; Nora Goldschlager, MD; Elsayed Z. Soliman, MD, MSc, MS. Published Online: May 4, 2015. doi:10.1001/jamainternmed.2015.1337. Conflict of Interest Disclosures: None reported.
jamainternalmedicine.com
2. Walder LA, Spodick DH. Global T wave inversion. J Am Coll Cardiol. 1991;17(7):1479-1485. 3. Qaqa AY, Suleiman A, Alsumrain M, Debari VA, Kirmani J, Shamoon FE. Electrocardiographic abnormalities in patients presenting with intracranial parenchymal haemorrhage. Acta Cardiol. 2012;67(6):635-639.
5. Lambert G, Naredi S, Edén E, Rydenhag B, Friberg P. Sympathetic nervous activation following subarachnoid hemorrhage: influence of intravenous clonidine. Acta Anaesthesiol Scand. 2002;46(2): 160-165. 6. Mannu GS. The non-cardiac use and significance of cardiac troponins. Scott Med J. 2014;59(3):172-178. 7. Duello KM, Nagel JP, Thomas CS, Blackshear JL, Freeman WD. Relationship of troponin T and age- and sex-adjusted BNP elevation following subarachnoid hemorrhage with 30-day mortality. Neurocrit Care. 2015.
4. Wybraniec M, Mizia-Stec K, Krzych L. Stress cardiomyopathy: yet another type of neurocardiogenic injury. Cardiovasc Pathol. 2014;23 (3):113-120.
(Reprinted) JAMA Internal Medicine Published online May 4, 2015
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Thomas Jefferson University User on 05/13/2015
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