Case Report and Brief Review

Inverted Takotsubo Cardiomyopathy

Amit S. Dande, MD, Lawrence I. Fisher, MD, Mark K. Warshofsky, MD
Amit S. Dande, MD, Lawrence I. Fisher, MD, Mark K. Warshofsky, MD
ABSTRACT: Takotsubo cardiomyopathy is a transient acute left ventricular dysfunction characterized by left ventricular apical akinesis and ballooning without obstructive coronary disease described predominantly in post-menopausal women in the setting of acute emotional or physical stress. Recent reports have described isolated transient basal akinesis (inverted takotsubo cardiomyopathy) in mostly female patients with acute neurologic disorders or pheochromocytoma. We describe a rare case of a 78-year-old male with inverted takotsubo cardiomyopathy in the setting of acute abdominal pain attributed to biliary colic. A review of published literature reveals that inverted takotsubo cardiomyopathy precipitated by acute stress rather than an acute neurologic disorder appears to be an extremely rare presentation in a male patient. We discuss the relevant literature regarding incidence and reported gender distribution of inverted takotsubo cardiomyopathy.
Case Report. A 78-year-old male ex-smoker, with a history of hypertension, hypercholesterolemia, peripheral vascular disease and carotid artery stenosis, presented with the chief complaint of sharp, aching left-sided chest pain of a few hours duration. The chest pain was acute in onset, continuous and progressive, accompanied with mild shortness of breath but no diaphoresis, dyspnea or palpitations. He denied fever, chills, nausea, vomiting, diarrhea, constipation or dysuria. Over the preceding days, he had had some mild right upper quadrant abdominal pain that had resolved spontaneously. A screening nuclear stress test performed 8 months prior had shown small fixed apical and lateral wall defects. On initial examination, pulse was 120 bpm, blood pressure was 176/88 mmHg and he was afebrile. HEENT, neck, cardiovascular and lung exams were unremarkable. The abdomen was soft and non-distended, with mild tenderness in the right upper quadrant without guarding or rebound tenderness and normoactive bowel sounds. Murphy's sign was not present. Abnormal laboratory results were: white blood cells, 10,900/mm3 (reference range, 4–10,000/mm3), 13% monocytes (reference range, 4–12%), hemoglobin, 11.2 g/dl (reference range, 13.5–17 g/dl) and hematocrit, 33.5% (reference range, 37–50%). Serum bilirubin, alkaline phosphatase, transaminases, amylase and lipase were normal. An electrocardiogram (ECG) revealed sinus rhythm with diffuse ST depression and mild ST elevation in aVR and V1. The chest x-ray did not reveal an acute cardiopulmonary process and abdominal x-ray showed nonspecific bowel gas pattern. Initial troponin-I level was 0.18 ng/ml (reference range, ≤ 0.04 ng/ml) with normal CK. Serum D-dimer was 976 ng/ml (reference range, ≤ 500 ng/ml) and BNP was 803 pg/ml (reference range, ≤ 100 pg/ml). Abdominal computed tomography (CT) scan showed gallbladder wall thickening and biliary dilation with a large gallstone in the lumen of the gallbladder. Because of the new ECG abnormality suggestive of left main or proximal left anterior descending artery stenosis, abnormal troponin and multiple coronary artery disease risk factors, he was treated for acute coronary syndrome and underwent urgent cardiac catheterization that revealed nonobstructive coronary artery disease. Left ventriculography showed an akinetic base with hypercontractile apex. His anticoagulation was discontinued while he remained on an oral beta-blocker and ACE-inhibitor. Cardiac enzymes showed further rise with peak CK of 329 (reference range, 0–170 U/L), CK-MB of 7.6 (reference range, ≤ 5 ng/ml), and TnI of 1.08 ng/ml (reference range, ≤ 0.04 ng/ml). His chest pain and dyspnea gradually improved. His ECG also improved, although it remained mildly abnormal at discharge. A V/Q scan found low probability for pulmonary embolism and abdominal ultrasound confirmed the CT scan findings. His abdominal pain and leukocytosis resolved spontaneously and he was discharged home in stable condition with a diagnosis of "inverted" takotsubo cardiomyopathy in the setting of acute abdominal pain presumed to be biliary colic. At a follow-up visit at 1 month, ECG had reverted to baseline and an echocardiogram revealed complete resolution of wall motion abnormalities. Discussion. Stress cardiomyopathy or takotsubo cardiomyopathy was initially described in 1991 by Satoh et al1 as a transient cardiomyopathy precipitated by acute emotional or physical stress where angiography revealed normal coronary arteries and left ventriculography revealed apical akinesis and/or ballooning with a hypercontractile base. The overall incidence is reported to be around 1–2% of troponin-positive acute coronary syndrome patients,2 and postmenopausal women make up an overwhelming majority of cases. A variant was subsequently described with mid-ventricular akinesis and hypercontractile apex and base.3,4 Thereafter, reports5,6 of patients admitted with acute coronary syndrome and antecedent stressful events described patients with basal and midventricular akinesis. In one series, 40% of all takotsubo cases (n = 35) had mid-ventricular dysfunction,2 with only 2 male patients (1 with apical and 1 with mid-ventricular variant). This report also compared demographic, clinical, laboratory and angiographic parameters between the 2 groups, and found no significant differences. In 2005, a case series7 described a pattern of isolated left ventricular basal hypokinesis with normal apical contractility (labeled 'inverted tako-tsubo') in 4 patients with acute cerebral disorders, all of whom had normal coronary arteries or non-obstructive coronary disease. In a prospective study of cardiac wall motion abnormalities in 173 patients with subarachnoid hemorrhage,8 echocardiography revealed basal and midventricular akinesis to be more common than apical akinesis. In a review of stress-related cardiomyopathy syndromes,9 isolated left ventricular basal dysfunction was recognized as a morphologic variant of both stress-induced cardiomyopathy as well as neurogenic stress cardiomyopathy. Pathology findings10 from a case of "neurogenic" inverted cardiomyopathy in a patient with acute subarachnoid hemorrhage described sparse foci of myocyte necrosis with contraction bands in the akinetic areas of the myocardium. Contraction band necrosis is caused by massive catecholamine release and this finding is similar to autopsy findings from stress cardiomyopathy patients,11 suggesting a similar pathogenesis for the 2 presentations. Differential expression of beta-adrenergic receptors in the apex compared to the base has been postulated to explain the wall motion abnormality in stress cardiomyopathy. However, patients have been reported to develop a different morphologic variant in rare recurrences.12 In our review of recent literature, the inverted tako-tsubo pattern has been reported predominantly in women with pheochromocytoma13–21 or acute neurologic disorders, such as cerebral hemorrhage or head injury.7,22–24 Sporadic reports of non-neurogenic presentations (presumably in the absence of antecedent stress), such as during infusion of catecholamines,6,25,26 amphetamine abuse,27 alcoholic pancreatitis,28 sepsis, post-partum29 and with anagrelide infusion,30 have been published in the last few years; all patients reported were women. In a large review (n = 107) of stress cardiomyopathy,31 a 1% incidence of basal/midventricular akinesis was reported, but the gender distribution was not specified. A recently published review comparing clinical characteristics of apical and non-apical variants of non-neurogenic stress cardiomyopathy32 reported a higher rate of heart failure and complications in patients with the apical variant. Notably, in a total sample size of 38 patients, all 9 patients with the non-apical variant were females. A recently published case report described a 30-year-old male with pheochromocytoma with inverted takotsubo pattern on left ventriculography.33 The patient we describe presented with inverted takotsubo cardiomyopathy in the absence of an acute neurologic disorder or pheochromocytoma. Although neurogenic/pheochromocytoma-related stress cardiomyopathy has been reported in males (also rare), we could find only 1 prior report34 that described a 21-year-old male with acute appendicitis who developed inverted takotsubo cardiomyopathy. Thus, this appears to be an extremely rare presentation in a male patient. Interestingly, the only identifiable antecedent stressor in this patient was mild abdominal discomfort prior to presentation presumed to be biliary colic.


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From the Division of Cardiology, Danbury Hospital, Danbury, Connecticut. The authors report no conflicts of interest regarding the content herein. Manuscript submitted June 16, 2010, provisional acceptance given July 26, 2010, final version accepted August 30, 2010. Address for correspondence: Mark K. Warshofsky, MD, Danbury Hospital, 24 Hospital Ave., Danbury, CT 06810. Email: