Takotsubo cardiomyopathy, also known as transient left ventricular apical ballooning syndrome (TLVABS), is an entity described as stress-induced cardiomyopathy with characteristic left ventricular (LV) apical and mid-wall dysfunction and ballooning mimicking acute myocardial infarction (MI).1,2 Herein, we present a case of TLVABS, possibly induced by preoperative emotional stress.
A 63-year-old woman was scheduled to undergo tympanoplasty and mastoidectomy for chronic otitis media. Her medical history was significant for anxiety, tobacco use (40 pack-years), and asthma. Her medications included buspirone and inhaled fluticasone. The patient had no history or symptoms of coronary artery disease (CAD), but she underwent a nuclear stress test 10 mo before, which showed no perfusion defects, and transthoracic echocardiography (TTE) was normal with an ejection fraction (EF) of 60%. An electrocardiogram (ECG) was obtained 11 days before surgery and was normal (Fig. 1).
On the day of surgery, the patient stated that she was anxious about surgery and under great stress from work. The patient was given 1 mg of midazolam in the operating room. Her arterial blood pressure was 130/82, heart rate 91 bpm, and T-wave inversions were noted in leads II and V5. She was otherwise asymptomatic and denied chest pain. A 12-lead ECG showed diffuse deep T-wave inversions and a prolonged QT interval (QTc 519) (Fig. 1).
Surgery was cancelled and a TTE was performed, showing a mildly dilated LV, with akinesis of the entire apex of the heart extending circumferentially into the mid-wall cavity with basal sparing, and an EF of 35%-40% (Fig. 2). The findings were consistent with Takotsubo cardiomyopathy, but acute ischemia could not be excluded. Therefore, the patient underwent cardiac catheterization.
Coronary angiography revealed diffuse noncritical CAD. The left ventriculogram demonstrated anteroapical akinesis with hyperkinesis of the base (Fig. 3). She was admitted to the intensive care unit and was treated with aspirin, metoprolol, enalapril, atorvastatin, and a heparin infusion. Over the course of hospitalization, the patient remained asymptomatic and serial troponin and creatine kinase measurements were all within normal limits. Repeat TTE 2 days later still showed depressed ventricular function, but there was improvement in apical contractile function with less ballooning. She was discharged 2 days later receiving metoprolol, aspirin, atorvastatin, and alprazolam. TTE performed 15 wk after the initial event showed complete normalization of ventricular function, and an ECG was also normal. About 17 months after this event, the patient had the planned surgery without recurrence of TLVABS or complications.
Takotsubo Cardiomyopathy or TLVABS was first recognized in Japanese patients and reported in 1990.3 The findings of circumferential LV apical and mid-wall dysfunction with ballooning and basal sparing led to its name, because the heart resembled a round-bottomed, narrow-necked Japanese fishing pot used to catch octopus (tako = octopus, tsubo = pot). The syndrome is typically preceded by an episode of emotional or physiologic stress leading to the use of other names such as “broken heart syndrome” or “stress cardiomyopathy.” In 2008, Bybee and Prasad2 proposed modified Mayo Clinic Criteria for the diagnosis of TLVABS (Table 1). The criteria included the finding of transient LV wall motion abnormalities involving the apical and/or midventricular segments with wall motion abnormalities extending beyond a single epicardial coronary distribution, the absence of obstructive CAD or plaque rupture, and new ECG abnormalities (ST segment elevation or T-wave inversion) or troponin elevation.
Systematic reviews regarding TLVABS have been published, and the majority of cases have been described in postmenopausal women.1,2 The most frequent presenting symptom was chest pain, followed by dyspnea and syncope. The most common ECG findings at presentation were ST-elevations in the precordium and diffuse T-wave inversions; bundle-branch blocks and QT-interval prolongation were also reported. There were small cardiac enzyme elevations in the majority of patients, which peaked very early as opposed to the delayed peak elevations seen in typical atherosclerotic MIs. No patient studied had a coronary stenosis more than 50%.
In a 19-patient case series of stress-induced cardiomyopathy by Wittstein et al.,4 about half the patients presented after receiving news of an unexpected death. Within 48 h of presentation, all patients had marked QT interval prolongation and 18 patients had deep symmetrical T-wave inversions. Seven had pathological Q-waves across the precordium, which resolved by the time of hospital discharge. The median initial EF was 20%, which improved to 45% by Day 4, and completely normalized on 3-wk follow-up. Thirteen patients underwent extensive neurohumoral evaluations and had their results compared with patients who presented with typical acute MIs. During the first few days after hospital admission, epinephrine, norepinephrine, and dopamine levels were found to be up to 34 times more than normal values and 2-3 times the levels of patients with acute MI.
Reported complications associated with TLVABS include left heart failure, dynamic intraventricular cavitary obstruction from basal hyperkinesia, systolic anterior motion of the mitral valve leading to mitral regurgitation and LV outflow obstruction, ventricular arrhythmias, LV mural thrombus, LV free-wall rupture, and death. In meta-analysis of Bybee et al.,1 common complications were heart failure (3%-44%) and intraventricular cavitary obstruction (13%-18%). The in-hospital mortality was 0%-8% with the largest series finding a mortality of 1%. One recent retrospective review by Bonello et al.5 found a higher mortality rate of 21% due to malignant ventricular arrhythmias. However, regional wall motion abnormalities and LV function returned to normal within days to weeks in most patients with TLVABS. Recurrence was low, with an incidence of 0%-8%.
The precise mechanism of TLVABS has yet to be elucidated. Enhanced sympathetic activity originating from the central nervous system is believed to be vital to its etiology. Sympathetic hyperactivity is common during the perioperative period, and cases of TLVABS have been reported in this period. There are three commonly proposed mechanisms for the myocardial dysfunction seen with TLVABS. High levels of norepinephrine released directly into the heart from cardiac sympathetic nerve terminals or high levels of circulating catecholamines can lead to direct myocyte injury, presumably associated with calcium overload and free-radical production.4,6 In histological studies, catecholamine-associated myocardial stunning may produce contraction band necrosis and interstitial mononuclear inflammatory patterns unlike the polymorphonuclear inflammation seen with MI.
Catecholamine induced microvascular endothelial dysfunction is an alternative mechanism for TLVABS.6,7 In a study of 16 patients with TLVABS who underwent cardiac catheterization, all patients had abnormal thrombolysis in MI flow grades.6 The thrombolysis in MI flow grade counts the number of cineframes for intracoronary injected contrast to reach distal landmarks. Abnormalities were present in all three coronary distributions in most patients despite the absence of obstructive coronary disease suggesting the presence of a generalized increase in microvascular resistance.
Finally, coronary vasospasm can be induced by high levels of catecholamines. Provocable multivessel epicardial coronary spasm was found in up to 43% of patients presenting with TLVABS in the Bybee et al.1 meta-analysis. Given the rapid recovery of the regional wall motion abnormalities seen in TLVABS and the lack of significant troponin elevations, we postulate that epicardial vasospasm is a less likely culprit for myocardial stunning.
It is unclear why the apex of the heart is predominantly affected. Although there is a greater density of sympathetic nerves in the base compared with the apex,8 there is evidence to suggest that the apex is more responsive to catecholamine excess9 and that there is a base to apex perfusion gradient in which the base receives more blood flow in the setting of catecholamine-mediated vasoconstriction.4,10 In some patients, the right ventricular apex is affected and cases of apical-sparing TLVABS have been reported.11 Given the low incidence (1.5%-2.2% of all coronary events), it is possible that there is a genetic predisposition. The relationship between the enhanced central nervous system sympathetic release from emotional or physiological stress leading to TLVABS and that of subarachnoid hemorrhage leading to ST-elevations, myocardial dysfunction, or cardiac enzyme release remains unclear. Lee et al.12 have described the occurrence of TLVABS in a small subset of patients after aneurysmal subarachnoid hemorrhage.
Management of TLVABS is mainly supportive. Because the symptoms are the result of left-sided congestive heart failure, typical therapies include diuretics and after-load reduction with angiotensin converting enzyme inhibitors. β-Blockers are used for the prevention of arrhythmia. Some patients require inotropic support; however, Wittstein et al.4 have advised caution in the use of inotropes given the already excessively high levels of circulating catecholamines and instead suggest mechanical circulatory support. Short-term anticoagulation is recommended to prevent apical mural thrombus. The role of nitrates or nondihydropyridine calcium channel blockers in those with vasospasm is less clear.
The presence of dynamic LV outflow obstruction should be evaluated by echocardiography, especially in those who are refractory to therapy or who become acutely hypotensive. Because inotropes may worsen dynamic obstruction, management involves the use of β-blockers for improved diastolic filling time and negative inotropy, as well as intravascular volume expansion and therapies to increase LV afterload.
Our patient was treated with a β-blocker, metoprolol, for the prevention of arrhythmia and an angiotensin converting enzyme inhibitor, enalapril, for afterload reduction. She initially received systemic anticoagulation with heparin but as the wall motion abnormalities resolved quickly, warfarin therapy was not instituted. Because this patient had some degree of underlying CAD, it is likely she would benefit from the long-term use of both β-blockers and aspirin for secondary prevention.13
The optimal time period for delay of elective surgery after an occurrence of TLVABS is unclear. In patients with nonischemic MIs, such as vasospasm or TLVABS, there are no issues related to atherosclerotic plaque stabilization. It is reasonable to delay elective surgery until regional wall motion abnormalities and ventricular function return to normal. There are reports of patients with presumed vasospasm undergoing uneventful elective surgery within a week of suffering MI.14,15
Finally, what should be done to prevent a recurrence when the patient returns to the operating room? There is no evidence to support any specific management strategy or drug therapy for the prevention of recurrence, however, providing a deeper level of anxiolysis before the operating room might be beneficial. Some have recommended achieving deep levels of anesthesia before intense stimulation, such as laryngoscopy,16 although there is not enough information to suggest that this strategy is useful. Studies on an animal model of TLVABS suggest that α- and β-blockade could normalize stress-induced ECG changes,17,18 so it might be rational to consider these drugs for prophylaxis.
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