Takotsubo cardiomyopathy following acute liver failure
Authors: Loretta L. Jophlin, David G. Koch
Journal: Hepatology (2014)

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy or "broken-heart" syndrome, is a reversible phenomenon of systolic dysfunction of the cardiac apex that can present similar to myocardial infarction.1 The coronary vasculature, however, is normal,1 and the proposed mechanism of the myocardial dysfunction is from catecholamine release causing reversible myocardial "stunning" during physical or emotional stress.1 To our knowledge, there are no documented cases of stress-induced cardiomyopathy in the setting of acute liver failure (ALF). We report a case of Takotsubo cardiomyopathy in a patient with acetaminophen-induced ALF. A healthy 32-year-old female was transferred to us for suspected acetaminophen-induced ALF. The week prior, she consumed 9 g of acetaminophen daily for back pain. On presentation to the referring facility, she had elevated aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] greater than 5,000 IU/L), coagulopathy (international normalized ratio [INR] 2.8), and an acetaminophen level of 35.8 μg/mL. She also had asterixis and mental slowing consistent with grade 2 encephalopathy. Other pertinent data included: lactate 14.3 mmol/L, ammonia 180 μg/dL, creatinine 1.4 μg/dL, and bilirubin 4.9 μg/dL. The patient had chest pain, but an electrocardiogram (EKG) and blood troponin I level were normal. Twelve hours later, EKG revealed ST-segment elevations in leads I and aVL (Fig. 1A), concerning for myocardial infarction. The troponin I level was elevated at 38.2 ng/mL and rose to 44.5 ng/mL 10 hours later. A transthoracic echocardiogram revealed hypokinesis of the antero-apical and apical septal region of the left ventricle (Fig. 2A,B) with reduced ejection fraction of 43%, and a left heart catheterization was angiographically normal (Fig. 2C). A diagnosis of Takotsubo cardiomyopathy was made based on echocardiographic findings and normal coronary angiography. The patient's ALF was successfully managed with intravenous N-acetyl-cysteine, preventing the need for liver transplantation. An EKG performed 72 hours after presentation demonstrated resolution of the ST-segment elevations (Fig. 1B), and she was discharged home with cardiac rehabilitation. The patient's electrocardiograms demonstrated (A) ST elevations 12 hours after presentation and (B) resolution of the ST elevations 72 hours later. Two-dimensional echocardiography revealed left ventricular systolic dysfunction with septal and apical akinesis in the setting of normal coronary arteries on angiography. (A) Apical four chamber view of systole, (B) apical four chamber view of diastole, and (C) coronary angiography. Although patients with ALF may have elevated levels of troponin I, its clinical significance is unclear.2, 3 Reports have shown that nearly 75% of patients with ALF have elevated troponin I and this elevation is associated with worse clinical outcomes (i.e., greater risk of hepatic coma and death).4, 5 While troponin I is both sensitive and specific for myocardial injury,5 it has been proposed that its elevation in ALF is nonspecific and secondary to metabolic stressors.2 Additionally, ST-segment changes and cardiac wall motion abnormalities have been described in ALF patients, but neither was associated with elevated levels of troponin I, as was seen in our patient.2 Further work should be done to characterize the mechanism of troponin I elevation during ALF as well as its clinical significance. Since Takotsubo cardiomyopathy is thought to occur in the setting of excessive catecholamines,1 it is conceivable that ALF could cause such an endogenous catecholamine release,6 resulting in our patient's cardiac manifestations. Additionally, there is a report of Takotsubo cardiomyopathy occurring in a cirrhosis patient who presented in shock and received epinephrine for resuscitation.7 It is unclear if the cardiac substrate is more vulnerable to catecholamine-induced injury in the setting of chronic liver disease. In summary, ALF patients with elevated troponin I should have echocardiography and EKG, particularly if liver transplant is considered. We propose that Takotsubo cardiomyopathy may be an unappreciated phenomenon in this patient population.