Diagnostics

Electrocardiographic T-wave changes underlying acute cardiac and cerebral events

John N. Catanzaro MD?, Perwaiz M. Meraj MD, Shuyi Zheng MD, Gregory Bloom MD, Marie Roethel MD, Amgad N. Makaryus MD

North Shore University Hospital, Manhasset, NY 11030, USA

Received 22 October 2007; accepted 24 October 2007

Abstract T-wave inversions produced by myocardial infarction (MI) are classically narrow and symmetric. Electrocardiography T-wave changes including low-amplitude and abnormally inverted T waves may be the result of noncardiac path physiology. We present a series of cases that presented with different electrocardiography T-wave changes. The first case involved a 64-year-old woman who presented to the emergency department with diffuse splayed T-wave inversions and was found to have an MI in the context of an acute cerebrovascular accident. We contrasted this case with that of a 76-year- old man with hypercholesterolemia who presented with T-wave widening and a prolonged QT interval and was found to have a subarachnoid hemorrhage secondary to a basilar aneurysm and no MI. Several mechanisms have been suggested to explain the cardiac and Cerebral injury, including microvascular spasm and increased levels of circulating catecholamines. Accurate interpretation of T-wave changes can assist the clinician toward a timely therapeutic intervention and accurate diagnosis.

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Introduction

The T wave is the electrocardiographic manifestation of ventricular repolarization, or phase 3 repolarization, of the cardiac electrical cycle. With complete depolarization of the myocardium (Phase 2 repolarization), voltage across the myocyte approaches 0. The positive voltage associated with the development of the T wave results from spontaneous repolarization of the myocytes, epicardial repolarizing earlier than endocardial cells. The electrical wave opposes depolar- ization, with an electrically negative pericardium relative to the rest of the myocardium, producing a deflection of positive voltage. The normal T wave is usually in the same direction as the QRS complex except in the right precordial

* Corresponding author. Division of Cardiology, Department of Medicine, North Shore University Hospital, Manhasset, NY 11030, USA. Tel.: +1 516 562 0100; fax: +1 516 488 7059.

E-mail address: [email protected] (J.N. Catanzaro).

leads. The normal T wave is also asymmetric with the first half moving more slowly than the second half. In the normal electrocardiogram (ECG), the T wave is always upright in leads I, II, V₃ through V₆, and always inverted in Lead aVR [1]. The other leads are variable depending on the direction of the QRS and the age of the patient.

T-wave changes may be the result of many cardiac and nonCardiac conditions. The differential diagnosis of acute T- wave changes can be vast, encompassing cardiovascular as well as neurologic systems. Cardiovascular etiologies of T- wave inversions include Q-wave and non-Q-wave MI (evolving anteroseptal MI), myocardial ischemia, subacute or old pericarditis, myocarditis, myocardial contusion, idiopathic apical hypertrophy, and even right or left ventricular hypertrophy with “strain.” Neurologic causes of T-wave changes include central nervous system diseases (which can prolong the QT interval) such as subarachnoid hemorrhage, subdural hematoma, and acute Cerebrovascular accidents (CVAs). Acute myocardial infarction (MI) often

0735-6757/$ - see front matter (C) 2008 doi:10.1016/j.ajem.2007.10.017

occurs in the setting of acute stroke. However, the diagnosis of MI is complicated by the fact that clinical symptoms such as chest pain may not accompany myocardial damage in acute stroke. In addition, the stress of acute stroke may cause nonspecific elevations of the biochemical markers of myocardial damage, as well as various ECG abnormalities consistent with early repolarization and ischemic-like changes [2,3]. Infarction or ischemia may result in a delay in myocyte repolarization. In the temporal evolution of an MI, the appearance of Abnormal Q waves is followed by T- wave inversions. A subgroup of patients with unstable angina presents with abnormal T-wave inversions, either symmetrical or biphasic in the precordial leads V₂ and V₃, termed Wellen syndrome [4-6].

Case summaries

Case 1

A 64-year-old woman with a medical history of diabetes mellitus presented to the emergency department (ED) with vertigo. The vertigo began the same day and was associated with nausea and vomiting. Substernal chest pain began after administration of anticholinergics. An electrocardiogram revealed a normal sinus rhythm with deep symmetrical anterior and precordial T-wave inversions, which were widely splayed (Fig. 1). The patient was taken to cardiac catheterization, which revealed a normal left main anterior descending artery, a 80% tubular stenosis in the mid anterior descending artery, and a small filling defect consistent with a thrombus. Percutaneous coronary inter-

vention was undergone in the mid left anterior descending coronary artery. The circumflex and right coronary arteries were normal without obstruction. Cardiac enzymes had trended up initially before the intervention, with a peak troponin I of 0.52 ng/mL, a peak Creatine phosphokinase of

154 IU/mL, with a creatine kinase-MB percentage of 5.5%. A subsequent computed tomographic (CT) study for persistent vertigo revealed multiple lacunar infarcts and periventricular changes, which were age indeterminate. Thus, a magnetic resonance study was performed for further evaluation, which revealed an acute intralenticular area of ischemia (Fig. 2). Echocardiogram postcatheteriza- tion was normal with respect to the size and function of atria and ventricles. There were no wall motion abnorm- alities and the ejection fraction within normal limits. After the cardiac catheterization, the patient remained without chest pain. She remained in the coronary care unit for 4 days after which she was discharged on medication for coronary artery disease and prophylactic pharmacotherapy for an acute CVA.

Case 2

A 76-year-old man with a history of hypercholesterolemia and prostate cancer went to sleep with no complaint. In the middle of the night, his spouse noted that he was not moving and almost not breathing. She called 911 and paramedics found the patient to be breathing agonally. He was intubated in the field and brought to the ED. The spouse denied any complaints that her husband may have mentioned to her. Physical examination revealed a blood pressure of 135/98

Fig. 1 Electrocardiogram of patient 1 showing deep symmetric widely splayed T waves.

Fig. 2 Magnetic resonance image showing a left parietal infarct adjacent to the atria of the left lateral ventricle along with periventricular white matter Ischemic changes.

mm Hg and pulse of 102/min. The patient had been paralyzed with medications in the field to allow for intubation and thus a neurologic examination could not be performed upon arrival to the ED.

An ECG was performed and revealed sinus tachycardia at about 100/min with 1 to 2 mm ST-segment elevations with broad-based T waves in leads II, aVL, aVF, and V₂ through V₆ and QT prolongation (Fig. 3). Concern was raised about an acute ischemic event. Cardiac enzyme biomarkers were normal and remained normal over the course of the hospitalization ruling out a MI. computed tomographic scanning of the brain revealed diffuse subarachnoid hemorrhage with associated increased density in the basilar cisterns, sylvan fissures, intrahemispheric region, and in multiple sulci. Hypodensities were also noted in the white matter adjacent to the bilateral frontal horns and were felt to represent chronic microvascular ischemic changes. Further examination with 3-dimensional CT reconstruction revealed the presence of a 1-cm basilar tip aneurysm, which was felt to be the cause of the hemorrhage. A ventriculostomy drain was placed and the patient underwent surgery for the aneurysm with interval improvement and recovery.

Discussion

Burch et al [7] first described the association of CVA and ECG changes in 1954. Most commonly seen on the ECG were T-wave inversions, prolonged QT intervals, large U waves, and ST-segment abnormalities. Although most of the patients had hemorrhagic CVAs, these changes were seen in ischemic CVA, intracerebral tumors, and

Fig. 3 Electrocardiogram of patient 2 showing sinus tachycardia at 100/min with 1 to 2 mm ST-segment elevations with broad-based T waves in leads II, aVL, aVF, and V₂ through V₆ and QT prolongation.

trauma [8,9]. The predominant theory behind these ECG changes involve the neurohumoral systems, where surges of catecholamine and sympathetic outflow instigate not only the electrical abnormalities but can also lead to physical myocardial damage [10,11]. It has been shown that stimula- tion of certain cortical and brain stem areas can reproduce the ECG changes aforementioned.

Results of human insular cortex stimulation suggest right- sided dominance in sympathetic Cardiovascular effects and left-sided dominance in parasympathetic effects [12]. In addition, Animal experimentation using a rat model with Middle cerebral artery occlusion, which results in a consistent lesion of brain including the insular cortex, directly addresses the role of lateralization of brain hemi- sphere, the site of cerebral infarction, and the effect of age on the ECG perturbations that develop after stroke [13,14]. Therefore, the insular cortex is thought to be one of the most important sites of control of autonomic function [15]. Hemorrhage into the sylvian fissure possibly stimulates the insular cortex mechanically and chemically and induces sympathetic cardiovascular effects such as ECG changes and blood pressure elevation. Patients with right-sided hemi- spheric infarction show significantly reduced circadian Blood pressure variability and a higher frequency of nocturnal blood pressure increase compared with patients with left- sided infarction. Right-sided infarction is also associated with higher serum norepinephrine concentrations, and the ECG more frequently shows abnormalities such as QT prolongation and arrhythmia [16,17].

In general, T-wave abnormalities can provide added evidence to support clinical diagnosis. Except in hyperka- lemia, a T-wave abnormality alone is not diagnostic of any

particular condition. The T wave must be considered along with QRS and ST-segment abnormalities. T waves will usually be abnormal in ventricular hypertrophy, Left bundle-branch block, chronic pericarditis, and in electrolyte abnormality. In chronic pericarditis, T waves show wide- spread inversion, not corresponding to any coronary artery distribution. General inversion of T waves can also be due to an evolving global subendocardial infarct. Several hours after an infarct, T waves begin to invert and may persist for months. The mechanism involves a repolarization vector opposite to that of a normal individual. This nonspecific finding of a MI must be used in correlation with the rest of the ECG and clinical presentation. Also, other methods for diagnosing acute myocardial injury are necessary for a definitive diagnosis. Examples of such methods are echocardiography to detect cardiac-wall motion, laboratory tests to detect elevated levels of biochemical markers of myocardial injury, autopsy, and thallium. The patient presenting with T-wave changes should be questioned regarding past or present symptoms of myocardial ischemia including chest pain. In addition, the wide differential diagnosis surrounding T-wave inver- sion can be simplified by taking into account the interval and shape of the inversion (Fig. 4). A history of athletic training, mental obtundation, or a signs and symptoms of stroke could also explain the findings. Physical findings of a cardiomyopathy could lead one to consider a hyper- trophic cardiomyopathy (Apical hypertrophy is associated with deeply inverted T waves across the anterior precordium.) In conjunction, an accurate neurologic history and examination must be undertaken in a patient who presents with neurologic symptoms.

Fig. 4 Analysis of T-wave inversion characteristics.

Conclusion

The ischemic and hemorrhagic CVAs, respectively, seen in cases 1 and 2 illustrate an atypical Electrocardiographic presentations of suspected MIs with a concomitant cere- brovascular event. Whereas the first case demonstrated the concomitant event of an MI and CVA, the second further proves the point that atypical electrocardiographic changes occur with either ischemic or hemorrhagic CVAs. Although this has been proven many times before, the etiology of this still proves elusive. Several mechanisms have been suggested to explain the acute reversible cardiac and central nervous system injury, including microvascular spasm and increased levels of circulating catecholamines. We have described here a protocol to aid in the evaluation of atypical T-wave changes. Accurate interpretation of T-wave changes taking into account the detail of the shape and symmetry, as displayed in these cases, can assist the clinician toward a more timely therapeutic intervention and accurate diagnosis.

References

1. Kasper DL, Braunwald E, Fauci A, Hauser S, Longo D, Jameson JL, editors. Harrison’s principles of internal medicine. 16th ed. New York (NY): McGraw-Hill Professional; 2005. p. 1239-40.
2. Sharkey SW, Shear W, Hodges M, Herzog CA. Reversible myocardial contraction abnormalities in patients with an acute noncardiac illness. Chest 1998;114(1):98-105.
3. Hayden G, Brady WJ, Perron AD, Somers MP, Mattu A. Electro- cardiographic T wave inversion: differential diagnosis in the chest pain patient. Am J Emerg Med 2001;19:252-62.
4. Goldberger AL. Myocardial infarction: electrocardiographic differen- tial diagnosis. 4th ed. St. Louis: Mosby-Year Book; 1991.
5. Renkin J, Wijns W, Ladha Z, et al. Reversal of segmental hypokinesis by coronary angioplasty in patients with unstable angina, persistent T wave inversion, and left anterior descending coronary stenosis: additional evidence for Myocardial stunning in humans. Circulation 1990;82:913-9.
6. de Zwann C, Bar FW, Wellens HJJ. Characteristic electrocardiographic pattern indicating a critical stenosis high in left anterior descending coronary artery in patients admitted because of impending myocardial infarction. Am Heart J 1982;103:730-6.
7. Burch GE, Meyers R, Abildskov JA. A new electrocardiographic pattern observed in cerebrovascular accidents. Circulation 1954;9: 719-23.
8. Walder LA, Spodick DH. Global T wave inversion. J Am Coll Cardiol

1991;17:1479-85.

1. Oppenheimer SM, Cechetto DF, Hachinski VC. Cerebrogenic cardiac arrhythmias. Cerebral electrocardiographic influences and their role in sudden death Arch Neur 1990;47:513-9.
2. Tokgozoglu SL, Batur MK, Topcuoglu MA, et al. Effects of stroke localization on cardiac autonomic balance and sudden death. Stroke 1999;30:1307-11.
3. Ramani A, Shetty U, Kundaje GN. electrocardiographic abnormalities in cerebrovascular accidents. Angiology 1990;41:681-6.
4. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology 1992;42: 1727-32.
5. Cechetto DF, Wilson JX, Smith KE, Wolski D, Silver MD, Hachinski VC. Autonomic and myocardial changes in middle cerebral artery occlusion: stroke models in the rat. Brain Res 1989;502:296-305.
6. Hachinski VC, Wilson JX, Smith KE, Cechetto DF. Effect of age on autonomic and Cardiac responses in a rat stroke model. Arch Neurol 1992;49:690-6.
7. Oppenheimer SM. Neurogenic Cardiac effects of cerebrovascular disease. Curr Opin Neurol 1994;7:20-4.
8. Sander D, Klingelhofer J. Changes of circadian blood pressure patterns and cardiovascular parameters indicate lateralization of sympathetic activation following hemispheric Brain infarction. J Neurol 1995;242: 313-8.
9. Klingelhofer J, Sander D. Cardiovascular consequences of clinical stroke. Baillieres Clin Neurol 1997;6:309-35.