Rationale and design of BROKEN-SWEDEHEART: a registry-based, randomized, parallel, open-label multicenter trial to test pharmacological treatments for broken heart (takotsubo) syndrome.

BACKGROUND: Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial. STUDY DESIGN AND OBJECTIVES: BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1,000 patients. Study 1 (adenosine hypothesis) will evaluate 2 coprimary end points: (1) wall motion score index at 48 to 96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48 to 96 hours (evaluated in 1,000 patients). The primary end point in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48 to 96 hours. CONCLUSIONS: BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as 2 parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS. CLINICAL TRIALS IDENTIFIER: The trial has been approved by the Swedish Medicinal Product Agency and the Swedish Ethical Board and is registered at ClinicalTrials.gov (NCT04666454).

Successful treatment of a severe Takotsubo syndrome case complicated by liver abscess.

The main manifestations of Takotsubo syndrome (TTS) are a spherical expansion of the left ventricle or near the apex and decreased systolic function. TTS is mostly thought to be induced by emotional stress, and the induction of TTS by severe infection is not often reported. A 72-year-old female patient with liver abscess reported herein was admitted due to repeated fever with a history of hypertension and impaired glucose tolerance. Her severe infection caused TTS, and her blood pressure dropped to 80/40 mmHg. IABP treatment was performed immediately and continued for 10 days, and comprehensive medication was administered. Based on her disease course and her smooth recovery, general insights and learnings may be: Adding to mental and other pathological stress reaction, serious infections from pathogenic microorganism could be of great important causation of stress reaction leading to TTS, while basic diseases such as coronary heart disease, hypertension, and diabetes were be of promoting factors; In addition to effective drug therapies for TTS, the importance of the timely using of IABP should be emphasized.

Prognostic impact of antiplatelet therapy in Takotsubo syndrome: a systematic review and meta-analysis of the literature.

While the most recent evidence suggests a lack of benefit, antithrombotic therapy is still extensively prescribed in patients with Takotsubo syndrome (TTS). The objective of this study was to determine whether patients with TTS benefit from anti-aggregation, in terms of either short-term or long-term outcomes. A systematic review and meta-analysis was conducted. A comprehensive search of the literature included MEDLINE, Cochrane Library, Clinicaltrials.gov, EU Clinical Trial Register, References, and contact with the authors. Methodological quality assessment and data extraction were systematically performed. The review adhered to the PRISMA framework guidelines. A total of 86 citations were identified, six being eligible for inclusion, for a total of 1997 patients. One of them considered both short-term and long-term outcomes. One reported outcomes during the index event, while the remaining four focused on potential long-term benefits. They were all retrospective cohort studies.Based on our data, the long-term use of antiplatelet therapy (AT) led to a significantly higher incidence of the composite outcome (OR: 1.54; 95% CI 1.09-2.17; p = 0.014) and overall mortality (OR 1.72; 95% CI 1.07-2.77; p = 0.027). The analysis did not show a statistically significant difference in TTS recurrences, stroke/TIA, and MI or CAD worsening with AT compared with no anti-aggregation. The AT in this settings did not show any clear benefit in improving the long-term outcomes, and it may be even detrimental and it may be detrimental. These results warrant further future research and the design of adequately powered randomized controlled trials focusing on the impact of aspirin on the outcomes in patients presenting with TTS.

Takotsubo Cardiomyopathy and ß-Blocker Poisoning: A Case Report.

ß-blocker poisoning is frequently observed because of its primary use for the treatment of cardiovascular diseases. The management of ß-blocker toxicity is dependent on the cardiovascular response and the severity of presentation. The present study describes the case of a patient with combined drug intoxication, ß-blocker, digoxin, benzodiazepines, acetaminophen and opiates in a suicidal attempt. A 63-year-old female was found somnolent and in a confused state at her residence following intentional poly-drug ingestion. Upon presentation, she was found to be hemodynamically unstable and was thus treated with vasopressors. The toxicological screening performed upon presentation was positive for polydrug ingestion. On day 3, the patient developed chest pain and ST-segment elevation in anterior leads, while transthoracic echocardiographic assessment disclosed a non-dilated left ventricle with moderate dysfunction and akinesia of the apex. Coronary angiogram revealed normal coronary arteries and, subsequently, the diagnosis of Takotsubo cardiomyopathy (TTC) was suspected. Supportive treatment was initiated with favorable evolution and left ventricular ejection fraction normalization. The management of hemodynamic instability with vasopressors should be judiciously administered in the treatment of ß-blocker poisoning, in view of the adverse effects on cardiac functions, including stress cardiomyopathy.

The effects of beta-blockers in patients with stress cardiomyopathy.

Beta-blockers are often used in the treatment of patients with stress cardiomyopathy without firm evidence of benefit. We conducted a retrospective case note review investigating the effects of beta-blockers on QT interval and heart rate in patients with stress cardiomyopathy over 3 days of hospital admission. We found no evidence of effects on QT interval from beta-blocker treatment in this condition.

Left Ventricular Thrombi and Embolic Events in Takotsubo Syndrome despite Therapeutic Anticoagulation.

INTRODUCTION: Takotsubo syndrome (TTS) may be complicated by left-ventricular (LV) thrombus formation in 1.3-5.3% of patients. Risk factors for thrombi comprise apical TTS, elevated levels of C-reactive protein and troponine, thrombocytosis, persisting ST segment elevation and right-ventricular involvement. Embolic risk appears high, and anticoagulation is recommended. CASE PRESENTATION: We present 3 females, aged 60-82 years, with TTS-associated LV thrombi and cerebral embolism despite therapeutic anticoagulation. Two patients showed apical and 1 patient midventricular ballooning. In 2 patients LV thrombi had not been present at the first echocardiographic examination. LV thrombi were multiple and highly mobile in 2 patients; 1 patient had a single immobile thrombus associated with spontaneous echocardiographic contrast (SEC). In each case, 3 of the described risk factors for LV thrombus formation were identified. The embolic stroke occurred 41-120 h after TTS symptom onset and 21-93 h after the initiation of therapeutic anticoagulation. Two patients were discharged with a neurological deficit, and 1 of them eventually died as a consequence of the stroke. LV thrombectomy to prevent embolism, which has been reported in a small number of cases, had not been considered in our patients. CONCLUSION: At present, the management of patients with TTS-related thrombi is still unclear, and further studies are urgently needed to assess the best methods for imaging and anticoagulation and to determine the role of thrombolysis and cardiac surgery. Until these studies are available, we suggest the following approach: patients with a TTS-related thrombus should be monitored by echocardiography while receiving anticoagulation. In case of highly mobile LV thrombi, the heart team may consider cardiac surgery to prevent systemic embolism. The role of SEC in TTS remains to be determined.

Takotsubo cardiomyopathy and pituitary apoplexy: a case report.

BACKGROUND: Takotsubo cardiomyopathy (TTC) has been widely recognized in recent decades and is triggered by either physical or psychological stressors. CASE PRESENTATION: A 70-year-old woman presented to the Emergency Department due to confusion, hypotension, fever, chills, and cough. She had a one-year history of diabetes insipidus. Pituitary function examination at admission revealed decreased thyroid, sex and adrenal hormones. Pituitary MRI displayed findings suggestive of nonhemorrhagic pituitary apoplexy. Electrocardiogram (ECG) revealed T-wave inversion and extended QT interval. Transthoracic echocardiogram (TTE) showed left ventricular apical dysplasia and ballooning, accompanied by reduced left ventricular ejection fraction. Coronary angiography (CAG) revealed no obvious coronary arterial stenosis. The left ventriculogram demonstrated an octopus clathrate appearance. Most ECG and TTE changes recovered 10 days later. CONCLUSIONS: To the best of our knowledge, this is the first report of newly diagnosed TTC associated with pituitary apoplexy.

Work-Related Stress Induced Takotsubo Cardiomyopathy.

Aim To report a case of Takotsubo cardiomyopathy secondary to a verbal altercation in an employee who presented with chest pain. Methods The clinical history was obtained from the patient's occupational health record and correspondence from her treating cardiologist. Results The patient was diagnosed with Takotsubo cardiomyopathy following investigations for chest pain. Her echocardiogram was diagnostic. She was treated with beta blockers and advised to have complete rest; she remained out of work for six months. Conclusion There are few published cases of work related Takotsubo cardiomyopathy; it poses a challenge to physicians to be cognisant of this condition in a case of chest pain following emotional turmoil.

Takotsubo cardiomyopathy: Review of broken heart syndrome.

Takotsubo cardiomyopathy, also known as broken heart syndrome, apical ballooning syndrome, or stress cardiomyopathy, occurs when a stressful emotional or physical event causes the left ventricle of the heart to dilate, leading to acute heart failure. The syndrome was first described in Japan in 1990. Signs and symptoms of Takotsubo cardiomyopathy are similar to acute myocardial infarction. The syndrome presents with similar ECG and biomarker indications, so it often goes undiagnosed until coronary angiography is performed and reveals no blockage. Treatment is largely supportive. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) may reduce the likelihood of recurrent episodes. Overall, the prognosis is very good, with about 95% of patients making a full recovery.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Multiple sclerosis broke my heart.

We report 5 cases of acute heart failure (AHF) related to multiple sclerosis (MS) relapses. AHF was inaugural in 3 patients, always preceded or accompanied by signs of brainstem dysfunction; it was severe, requiring intensive care management. Echocardiography showed left ventricular hypokinesis. No other cause of AHF has been found. All patients showed a new medullary lesion on brain magnetic resonance imaging. All had rapid and complete recovery of ventricular function after intravenous corticosteroids. We concluded that the cases represent a takotsubo phenomenon. Physicians should be aware of rare cases of takotsubo cardiomyopathy in MS relapses. Ann Neurol 2017;81:754-758.

Takotsubo syndrome with pulmonary embolism: a case report and literature review.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiac condition with reversible heart failure which is often triggered by psychological and physical stressful events. Although pulmonary embolism (PE) was reported as a trigger for TTS, the concurrence of TTS and PE has been rarely reported, let alone that triggered by PE. Here we describe a case of a postmenopausal female presenting with symptoms similar to myocardial ischemia, which may be caused by PE, and review the available literature that may help clinicians with their practice to similar situations since no published guidelines are available. CASE PRESENTATION: An 86-year-old female was referred to the emergency department for unrelieved chest tightness, shortness of breath and back pain. Cardiac biomarkers were mildly elevated and electrocardiogram displayed pathologic Q-waves, ST-segment elevation and inverted T-waves. Unexpectedly, coronary angiography was in absence of obstructed coronary atherosclerosis or acute plaque rupture. Chest computed tomography illustrated multiple pulmonary emboli in bilateral pulmonary arteries. She had suffered from long-term right lower extremity pain and experienced a long railway journey with less activity. Both echocardiogram and cardiac magnetic resonance demonstrated regional hypokinesia of left ventricle. She received anticoagulant and diuretic therapies, three-month follow up after discharge revealed uneventful recovery without any pulmonary emboli or regional motion abnormalities, thus she was retrospectively diagnosed with TTS caused by PE. CONCLUSION: TTS and PE are scarcely concurrent and PE can exert as a potential trigger for TTS. TTS is easily misdiagnosed, actively seeking possible risk factors of TTS is in favor of early diagnosis and timely intervention. TTS with PE is reversible, timely and effective treatments ensure the best possible outcome.

Clinical outcomes associated with catecholamine use in patients diagnosed with Takotsubo cardiomyopathy.

BACKGROUND: Recent hypotheses have suggested the pathophysiological role of catecholamines in the evolution of the Takotsubo syndrome (TTS). The extent of cardiac and circulatory compromise dictates the use of some form of supportive therapy. This study was designed to investigate the clinical outcomes associated with catecholamine use in TTS patients. METHODS: Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The study-patients were subsequently classified into two groups based on the need for catecholamine support during hospital stay (catecholamine group n = 93; 81%, non-catecholamine group = 21; 19%). The primary end-point of our study was all-cause mortality. RESULTS: Patients receiving catecholamine support showed higher grades of circulatory and cardiac compromise (left ventricular ejection fraction (LVEF) 39.6% vs. 32.7%, p-value < 0.01) and the course of disease was often complicated by the occurrence of different TTS-associated complications. The in-hospital mortality (3.2% vs. 28.5%, p < 0.01), 30-day mortality (17.2% vs. 51.4%, p < 0.01) as well as long-term mortality (38.7% vs. 80.9%, p < 0.01) was significantly higher in the group of patients receiving catecholamine support. A multivariate Cox regression analysis attributed EF ≤ 35% (HR 3.6, 95% CI 1.6-8.1; p < 0.01) and use of positive inotropic agents (HR 2.2, 95% CI 1.0-4.8; p 0.04) as independent predictors of the adverse outcome. CONCLUSION: Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTS patients receiving catecholamine support as compared to the other study-patients. These results need further evaluation in pre-clinical and clinical trials to determine if external catecholamines contribute to an adverse clinical outcome already compromised by the initial insult.

Temporarily increased stroke rate after Takotsubo syndrome: need for an anticoagulation?

BACKGROUND: Previous studies have reported slightly higher stroke rates in Takotsubo Syndrome compared to acute myocardial infarction. Our goal was to evaluate the temporal course of stroke rates and left ventricular recovery in patients with Takotsubo Syndrome. METHODS: We retrospectively examined the clinical and imaging data of 72 patients with Takotsubo Syndrome. The data collected came from January 2005 to March 2017. Left ventricular performance was evaluated by cardiovascular magnetic resonance imaging (MRI) in all patients during the acute phase of Takotsubo Syndrome and in a follow-up scan 2 months later. Acute stroke and major adverse clinical events, such as myocardial infarction or recurrence of Takotsubo Syndrome and death, were also determined for each patient at 30 days and 12 months after initial presentation. RESULTS: The MRI scans performed during the acute phase of Takotsubo Syndrome demonstrated apical ballooning with anterior wall motion dysfunction in 65 (90%) patients. Imaging performed 2 months later demonstrated resolution of this in 97% of those patients. Median left ventricular ejection fraction also significantly increased between both scans (49.5% vs. 64.0%, P < 0.001). We observed 9 (12%) events in the study population within 12 months of the initial diagnosis of Takotsubo Syndrome. Stroke had an event rate of 2.8% after 30 days and 4.2% after 12 months. CONCLUSIONS: Apical ballooning was found in the majority of our Takotsubo Syndrome patients on the MRI scans performed at presentation. This finding was subsequently associated with higher than expected stroke rates within 30 days of diagnosis and with rapid recovery of left ventricular function within 2 months of diagnosis. This suggests that rapid improvement in left ventricular morphology and function may facilitate the formation of cardiac emboli and consequently increase stroke rates in Takotsubo Syndrome. Although no guidelines currently exist for the treatment of Takotsubo Syndrome, these results may point to a potential role for temporary oral anticoagulation in high-risk patients. Future studies should examine if stroke rates after Takotsubo Syndrome have been underestimated.

Neutrophil-Initiated Myocardial Inflammation and Its Modulation by B-Type Natriuretic Peptide: A Potential Therapeutic Target.

Activation of neutrophils is a critically important component of the innate immune response to bacterial and chemical stimuli, and culminates in the "neutrophil burst", which facilitates neutrophil phagocytosis via the release of superoxide anion radical (O2-) from NADPH oxidase. Excessive and/or prolonged neutrophil activation results in substantial tissue injury and increases in vascular permeability-resulting in sustained tissue infiltration with neutrophils and monocytes, and persistent vasomotor dysfunction. Cardiovascular examples of such changes include acute and chronic systolic and diastolic heart failure ("heart failure with preserved ejection fraction"), and the catecholamine-induced inflammatory disorder takotsubo syndrome. We have recently demonstrated that B-type natriuretic peptide (BNP), acting via inhibition of activation of neutrophil NADPH oxidase, is an important negative modulator of the "neutrophil burst", though its effectiveness in limiting tissue injury is partially lost in acute heart failure. The potential therapeutic implications of these findings, regarding the development of new means of treating both acute and chronic cardiac injury states, are discussed.

Hydrogen sulfide attenuates cardiac injury in takotsubo cardiomyopathy by alleviating oxidative stress.

Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricular apical ballooning with the absence of coronary occlusion, which is an acute cardiac syndrome with substantial morbidity and mortality. It was reported that reduced endogenous hydrogen sulfide (H2S) levels may be related to various heart diseases. The present study investigated the mechanism by which H2S administration modulates and protects cardiac function in TCM rats. In order to establish a TCM model, Sprague Dawley (SD) rats were injected with a single dose of ß-adrenergic agonist isoprenaline (ISO). We found that ISO induced cardiac dysfunction, which was characterized by a significant decrease in left ventricular systolic pressure (LVSP), maximum contraction velocity (+dp/dtmax), maximum relaxation velocity (-dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP). Accordingly, we found that plasma and heart tissue H2S levels in TCM rats decreased significantly, and cardiac cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) expression were lower. Moreover, cardiac dysfunction in TCM was associated with oxidative stress response and reactive oxygen species (ROS) formation. NADPH Oxidase 4 (NOX4) and p67 protein expressions significantly increased in TCM cardiac tissues. In addition, Sodium hydrosulfide (NaHS) ameliorated ISO-induced cardiac dysfunction and reversed ISO-induced oxidative stress. This study revealed that H2S exerted cardioprotective effects by reducing NADPH oxidase, which reduced ROS formation and prevented oxidative stress. Our study provided novel evidence that H2S is protective in myocardial dysfunction in TCM rats and could be a therapeutic target for alleviating ß-adrenergic system overstimulation-induced cardiovascular dysfunction.

Evaluation of therapy management and outcome in Takotsubo syndrome.

BACKGROUND: To date there is no validated evidence for standardized treatment of patients with Takotsubo syndrome (TTS). Medication therapy after final TTS diagnosis remains unclear. Previous data on patient outcome is ambivalent. Aim of this study was to evaluate medication therapy in TTS and to analyze patient outcome. METHODS: Within an observational retrospective cohort study we analyzed our medical records and included 72 patients with TTS that underwent cardiovascular magnetic resonance imaging (CMR) after a median of 2 days interquartile range (IQR 1-3.5). We investigated medication therapy at discharge. Medication implementation and major adverse clinical events (MACE) were prospectively evaluated after a median follow-up of 24 months (IQR 6-43). Left ventricular function, myocardial oedema and late gadolinium enhancement were analyzed in a CMR follow-up if available. RESULTS: Antithrombotic therapy was recommended in 69 (96%) patients including different combinations. Antiplatelet monotherapy was prescribed in 28 (39%) patients. Dual antiplatelet therapy was recommended in 29 (40%) patients. Length of therapy duration varied from one to twelve months. Only in one case oral anticoagulation was prescribed due to apical ballooning with a left ventricular ejection fraction <30%. In all other cases oral anticoagulation was recommended due to other indications. ß-adrenoceptor antagonists and ACE inhibitors were recommended in 63 (88%), mineralocorticoid receptor antagonists were prescribed in 31 (43%) patients. After a median of 2 months (IQR 1.3-2.9) left ventricular function significantly recovered (49.1% ± 10.1 vs. 64.1% ± 5.7, P < 0.001) and myocardial oedema significantly decreased (13.5 ± 11.3 vs. 0.6% ± 2.4, P = <0.001) in the CMR follow-up. The 30-day mortality was 1%. MACE rate after 24 months was 12%. CONCLUSION: Although therapy guidelines for TTS currently do not exist, we found that the majority of patients were treated with antithrombotic and heart failure therapy for up to twelve months. Left ventricular function and myocardial oedema recovered rapidly within the first two months. Outcome analysis showed a low bleeding rate and a high short-term survival. Therefore, TTS patients might benefit from antithrombotic and heart failure therapy at least for the first two months.

Takotsubo cardiomyopathy complicated with apical thrombus formation on first day of the illness: a case report and literature review.

BACKGROUND: Takotsubo cardiomyopathy is characterized by transient systolic dysfunction of the apical and mid segments of the left ventricle in the absence of obstructive coronary artery disease. Intraventricular thrombus formation is a rare complication of Takotsubo cardiomyopathy and current data almost exclusively consists of isolated case reports and a few case series. Here we describe a case of Takotsubo cardiomyopathy with formation of an apical thrombus within 24 h of symptom onset, which has been reported in the literature only once previously, to the best of our knowledge. We have reviewed the available literature that may aid clinicians in their approach to the condition, since no published guidelines are available. CASE PRESENTATION: A 68-year-old Sri Lankan female presented to a local hospital with chest pain. Electrocardiogram (ECG) showed ST elevation, and antiplatelets, intravenous streptokinase and a high dose statin were administered. Despite this ST elevation persisted; however the coronary angiogram was negative for obstructive coronary artery disease. Echocardiogram revealed hypokinesia of the mid and apical segments of the left ventricle with typical apical ballooning and a sizable apical thrombus. She had recently had a viral infection and was also emotionally distressed as her sister was recently diagnosed with a terminal cancer. A diagnosis of Takotsubo cardiomyopathy was made and anticoagulation was started with heparin and warfarin. The follow up echocardiogram performed 1 week later revealed a small persistent thrombus, which had completely resolved at 3 weeks. CONCLUSION: Though severe systolic dysfunction is observed in almost all the patients with Takotsubo cardiomyopathy, intraventricular thrombus formation on the first day of the illness is rare. The possibility of underdiagnosis of thrombus can be prevented by early echocardiogram in Takotsubo cardiomyopathy. The majority of reports found in the literature review were of cases that had formed an intraventriclar thrombus within the first 2 weeks, emphasizing the importance of follow up echocardiography at least 2 weeks later. The management of a left ventricular thrombus in Takotsubo cardiomyopathy is controversial and in most cases warfarin and heparin were used for a short duration.