It Must Be Cardiac!

Background
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An 81-year-old woman presents to the emergency department (ED) with an altered mental status. The patient was in her usual state of health until she vomited several times earlier today. Her family attributed the vomiting to discontinuation of her metoclopramide therapy, which she was taking for diabetic gastroparesis. The medication was stopped because the patient's family was concerned that this medication was aggravating her facial dyskinesia. As the day progressed, the patient was noted to have difficulty communicating; she could neither understand commands nor verbalize simple phrases. In addition, she was noted to be unable to move her left upper extremity. The patient lives alone. She has no documented history of trauma but does have a history of repeated falls. She has a medical history of end-stage renal disease requiring hemodialysis, insulin-dependent diabetes mellitus, hypertension, and coronary artery disease that is poorly defined. Her medications include aspirin, insulin, sevelamer hydrochloride, simvastatin, labetalol, and enalapril.

On physical examination, the patient appears ill, with a temperature of 98.4°F (36.9°C), a blood pressure of 180/89 mm Hg, a heart rate of 72 bpm, and a respiratory rate of 14 breaths/min. Her oxygen saturation is 96% while breathing room air. The findings of the pulmonary, cardiac, and abdominal examinations are within normal limits. The neurologic examination, however, reveals a patient that is aphasic and has left hemiparesis. Her finger-stick blood glucose level is 112 mg/dL (6.2 mmol/L).

What is the most likely cause of this patient's ECG abnormalities?

Hint: Try to localize the abnormality.
a. Cerebrovascular disease–induced T-wave inversions
b. Hyperacute T-waves in acute myocardial infarction
c. Hyperkalemia
d. Digoxin toxicity

Discussion
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The patient's ECG demonstrated a sinus rhythm at a rate of 60 bpm, with a markedly prolonged QT interval of 680 msec (normal range for females, <470 msec) and deep, symmetric T-wave inversions most pronounced in the anterior precordial leads (V2-V6). Because of the patient's altered mental status and focal neurologic findings, a noncontrast computed tomography (CT) scan of the head was obtained, which demonstrated bilateral, frontal subdural hemorrhages (see Figure 2). The patient was admitted to the intensive care unit for further evaluation and treatment by the neurology and neurosurgical teams, as well as for consultation with the cardiology service.

Severe ECG changes mimicking acute myocardial infarction frequently complicate presentations of acute intracranial pathology, such as thrombotic or hemorrhagic stroke, subdural hematoma, epidural hematoma, seizures, and/or subarachnoid hemorrhage. Most commonly, ECG changes in these processes manifest as alterations in the pattern of repolarization, such as in the QT interval, ST segment, and/or T waves. A prolonged QT interval and prominent peaked or deeply inverted and symmetric T waves are commonly seen. Mayer et al described a pattern of QT prolongation and deep T-wave inversions in patients with acute subarachnoid hemorrhage.[1] The seminal description of ECG changes in acute stroke was made by Goldstein, who described the ECG changes in 150 patients and age- and sex-matched controls.[2] In this description, 92% of patients with stroke had some sort of ECG changes, with 45% of patients developing a prolonged QT interval, and 35% exhibiting ischemic-appearing T-wave inversions. The changes may occur soon after the neurologic event, or they can evolve over a few days. In addition to repolarization abnormalities on the ECG, arrhythmias such as premature ventricular contractions (PVCs), ventricular tachycardia, and bradycardia may occur as a consequence of the central nervous system (CNS) event. In Goldstein's study, 27% of patients with an acute stroke developed arrhythmias.[2]

The pathogenesis of ECG changes and cardiac arrhythmia in the setting of a CNS event involves alterations in the complex neural-cardiac pathways that are responsible for normal autonomic control of cardiac function. In the setting of acute stroke, autonomic tone is dysregulated by a predominant adrenergic surge of catecholamines (such as norepinephrine). In particular, involvement of the insular cortex by the CNS event is commonly associated with a surge in norepinephrine, and it is associated with an increased rate of arrhythmias and death.[3,4] Opinions vary as to whether left or right insular cortex involvement is most likely to lead to cardiac arrhythmias. Adrenergic overstimulation may lead to ventricular systolic dysfunction and wall motion abnormalities, with or without serum biochemical markers of myocardial necrosis. The classic description of adrenergically mediated cardiac dysfunction is termed "takotsubo cardiomyopathy"; it presents with apical wall motion abnormalities in the setting of severe emotional stress.[5] A recent report described a presentation of takotsubo-like apical ballooning in association with ischemic-like ECG changes and elevated serum cardiac biomarkers in the setting of acute subarachnoid hemorrhage.[6] Despite marked cardiac wall motion abnormalities during the acute presentation, a repeat echocardiogram 1 week after the event showed complete resolution of the cardiac regional wall motion abnormalities. The presence of regional wall motion abnormalities during acute stroke is a well-described entity. Kono et al performed coronary angiography in 12 patients with acute stroke symptoms and the presence of ischemic ECG changes and regional wall motion abnormalities. Despite the presence of focal wall motion abnormalities, none of these patients demonstrated significant coronary artery stenosis or evidence of coronary vasospasm. On follow-up echocardiographic examination, the regional wall motion abnormalities in these patients had resolved.[7]

When present in the setting of coronary artery disease, the deep, symmetric T-wave inversions similar to those seen in this patient (Figure 1) are also known by the eponym "Wellens syndrome". De Zwaan and Wellens first described these changes in 1982 in patients presenting with unstable angina.[8] Later, Haines and Wackers et al showed that these same ECG changes during unstable angina were associated with a 38% chance of an adverse cardiac event rate during the next 16 months, and that these changes had an 84% positive predictive value for >70% left anterior descending coronary artery stenosis at angiography.[9] Despite the association of this ECG pattern with significant coronary artery disease, in the setting of acute stroke this ECG pattern can be present without preexisting coronary artery disease.[1]

The determination of the causality of ECG changes seen in the patient described above requires careful attention to the neurologic and cognitive examination. Since patients who present with acute stroke also frequently have risk factors for the development of coronary artery disease, this ECG pattern can present a diagnostic dilemma. CNS-derived cardiac conditions can present with ECG changes mimicking cardiac ischemia and/or injury, focal wall motion abnormalities on echocardiography, and elevated biomarkers for cardiac injury. Therefore, these tests provide little diagnostic differentiation. Consequently, it is imperative to perform a rapid, but detailed, neurologic examination in patients who present to the ED with an ECG as described above in order to identify patients whose ECG changes may be related to an ongoing acute stroke. If the examination or clinical judgment warrants, rapid noncontrast CT scanning of the head or a magnetic resonance imaging (MRI) scan of the brain should be performed to evaluate for a CNS process.[1,2,3,4,6,10]

Once a patient has been identified as having ECG changes resulting from an acute stroke, it is reasonable for clinicians to perform echocardiography and serum biomarker analysis in order to potentially identify patients at a higher risk for cardiac adverse events. At a minimum, the presence of ECG changes during a CNS event warrants the placement of the patient on telemetry monitoring; however, given the frequency of ventricular arrhythmias (including ventricular tachycardia and fibrillation) in patients with acute stroke, placement of the patient in an intensive care unit solely for cardiac monitoring provides the highest level of safety. Treatments aimed at limiting adrenergic stimulation to the heart (beta-adrenergic receptor antagonists) can be given if the patient manifests evidence of cardiac dysfunction or injury. In cases of severe systolic dysfunction, supportive measures such as loop diuretics, supplemental oxygen, and/or endotracheal intubation may be necessary. While no randomized data support their use in stroke-mediated cardiac dysfunction, angiotensin-converting enzyme inhibitors (ACEI) and statin therapy are also reasonable options.[3,10]

Because of the overlapping risk profiles in patients with cerebrovascular and cardiovascular disease, once an acute CNS event has been treated, cardiac risk stratification with myocardial perfusion imaging may be performed. This serves to evaluate for potential underlying coronary artery disease that was "unmasked" by the stress of the CNS event. In the majority of patients with CNS-mediated ECG changes and cardiac dysfunction, however, the cause of their cardiac abnormalities is not significant coronary artery disease. Therefore, proceeding directly to coronary angiography in the absence of other compelling indicators is probably unwarranted.[10]

Despite the sometimes dramatic cardiac presentations in patients with acute stroke, the majority of these patients recover their cardiac function with supportive care. Patients should be monitored on telemetry until the ECG normalizes and the acute stroke symptoms stabilize. In patients with cardiac regional wall motion abnormalities, repeat echocardiography may be performed following normalization of the ECG to document resolution of the cardiac dysfunction.[10]

The patient in this case was admitted to the intensive care unit for cardiac monitoring, serial neurologic examinations, and further testing. An MRI of the brain confirmed a right-sided acute ischemic stroke, but the presence of the small subdural hemorrhages (likely the result of the patient's recurrent falls) prevented the use of antiplatelet therapy in this patient. The ECG changes normalized within 2 days and the cardiac enzymes remained within normal limits. An echocardiogram was performed on hospital day 2 which demonstrated moderate diastolic dysfunction, with no focal wall motion abnormalities. A repeat CT scan of the head on hospital day 4 showed no progression of the small subdural hemorrhages. The patient's neurologic exam did not change from her initial presentation and she was discharged to a skilled nursing facility on hospital day 5.

Special thanks are extended to Dr. John Vozenilek, MD, FACEP, for his contributions to the publication of this case.

Which of the following CNS conditions can cause changes in a patient's ECG?
a. Subarachnoid hemorrhage
b. Subdural hematoma
c. Thromboembolic stroke
d. All of the above
Which of the following is NOT a clinical feature of cardiac dysfunction during an acute stroke?
a. Long-term persistent cardiac regional wall motion abnormalities
b. Focal cardiac regional wall motion abnormalities
c. ST-segment depression
d. ST-segment elevation

The majority of cardiac regional wall motion abnormalities are focal during acute stroke, but resolve as the CNS event resolves. ECG changes may include either ST-segment depression or elevation.