Takotsubo cardiomyopathy

The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated electrocardiogram (ECG) changes mimicking an anterior wall myocardial infarction. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome the name takotsubo ("octopus trap") in Japan, where it was first described. Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms. Acute asthma, surgery, subarachnoid hemorrhage, chemotherapy, and stroke are examples of physical stressors. == Risk factors ==

Stress trigger Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful or emotional event. A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections – such as Parvovirus B19 – which occur more frequently during the winter. The relationship between thyroid function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary hyperthyroidism and a high set point of thyroid homeostasis (encoding type 2 allostatic load) are common phenomena. A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS. This observation was confirmed by results of the international GEIST registry, which demonstrated that thyrotoxicosis is associated with significantly increased fatality, whereas hypothyroidism indicates a better survival. ==Pathophysiology==

The cause of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed. It is well documented that elevated catecholamine levels have been implicated in the vast majority of TTS cases. Theories suggest a link between brain activation of stress-related biochemicals (including neuropeptides) and the effects these chemicals have on areas of the heart, especially neuropeptide Y. Specifically, adrenal stimulation by the sympathetic nervous system has been seen in cases ranging from physical events such as ischemic stroke, to emotional events such as depression or loss of a loved-one. How these increased levels of catecholamines act in the body to produce the changes seen with TTS is not clearly understood. Other researchers have shown that vasospasm is much less common than earlier thought. It has been observed that vasospasms, even in multiple arteries, do not correlate with the areas of myocardium that are not contracting. However, coronary artery vasospasm is still believed to contribute to the TTS disease process. The theory of vasospasm is not easily distinguished from microvascular dysfunction, and microvascular dysfunction could explain vasospasticity. A quarter of unselected patients with TTS who presented to an emergency department were found to have obstructive hypertrophic cardiomyopathy (HCM) on blinded echocardiographic analysis. These patients had septal thickening, systolic anterior motion (SAM) of the mitral valve, left ventricular outflow tract (LVOT) obstruction with mean peak outflow gradients of 71 ±40mmHg. Compared with normal controls, the patients with SAM had longer anterior mitral leaflets, thicker septum (16 ±4 mm), and anterior displacement of the mitral valve in LV cavity. Moreover, in the patients with SAM, distinctive characteristics of HCM, including the mitral valve abnormalities persisted after normalization of LV function. It had previously been hypothesized that LVOT obstruction was due to a geometric shape-change of the LV caused by ballooning. In contrast, this data and others indicate that SAM and the outflow obstruction, rather are the cause of the LV ballooning in these patients. Patients with obstructive HCM may develop acute LV ballooning that resembles TTS when latent obstruction becomes severe and unrelenting. This observation has supplemented previous reports that acute LV ballooning punctuated the course of 1% of obstructive HCM patients, occurring even in recent clinical trials of pharmacologic agents. The cause is afterload mismatch and supply-demand ischemia that frequently cause striking cardiographic abnormalities when LVOT gradients are more than 60 mmHg. Contributing to ischemia are intramural coronary narrowings in HCM due to intimal and medial hyperplasia of the arterioles. Acute LV ballooning due to SAM and LVOT obstruction can cause cardiogenic shock. The most common cause is thought to be a direct adverse effect on the cardiomyocytes and microvasculature that may be conceptualized as neurohumoral TTS. Another, occurring in a minority of TTS patients, is caused by acute LVOT obstruction with distinctive features of HCM. Both may be precipitated by acute emotional stress. • Apical stunning: This stunning is largely seen as a protective effect produced by the flood of excess catecholamines into the cardiac muscle cell. ==Diagnosis==

Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the Mayo Clinic. Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group, University of Gothenburg, Johns Hopkins University, the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the European Society of Cardiology. All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac troponin. It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by chest pain, shortness of breath, ST-segment elevation, T-wave inversion or QT-interval prolongation on ECG. Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant coronary artery disease. The ballooning patterns were classified by Shimizu et al. as takotsubo type for apical akinesia and basal hyperkinesia, reverse takotsubo for basal akinesia and apical hyperkinesia, mid-ventricular type for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and localised type for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction. File:Takotsubo ventriculography.gif|Left ventriculography during systole showing apical ballooning akinesis with basal hyperkinesis in a characteristic takotsubo ventricle File:Takotsubo left ventriculogram.jpg|Left ventriculogram during systole displaying the characteristic apical ballooning with apical motionlessness in a patient with takotsubo cardiomyopathy File:Takotsubo ultrasound.gif|(A) Echocardiogram showing dilatation of the left ventricle in the acute phase (B) Resolution of left ventricular function on repeat echocardiogram six days later File:Takotsubo ECG.JPEG|ECG showing sinus tachycardia and non-specific ST and T wave changes from a person with confirmed takotsubo cardiomyopathy File:UOTW 74 - Ultrasound of the Week 2.webm|Echocardiogram showing the effects of the disease ==Treatment==

The treatment of takotsubo cardiomyopathy is generally supportive in nature, for it is considered a transient disorder. Treatment is dependent on whether patients experience heart failure or acute hypotension and shock. In many individuals, left ventricular function normalizes within two months. Aspirin and other heart drugs also appear to help in the treatment of this disease, even in extreme cases. After the patient has been diagnosed, and myocardial infarction (heart attack) ruled out, the aspirin regimen may be discontinued, and treatment becomes that of support for the patient. While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes. It is important that the individual stay physically healthy while learning and maintaining methods to manage stress, and to cope with future difficult situations. Although the symptoms of takotsubo cardiomyopathy usually go away on their own and the condition completely resolves itself within a few weeks, some serious short and long-term complications can happen that must be treated. These most commonly include congestive heart failure and very low blood pressure, and less commonly include blood clotting in the apex of the left ventricle, irregular heart beat, and tearing of the heart wall. Therefore, early echocardiography is necessary to determine proper management. For those with obstructed LVOTs inotropic agents should not be used, but instead should be managed like patients with hypertrophic cardiomyopathy, (e.g. phenylephrine and fluid resuscitation). (MCS) with an intra-aortic balloon pump (IABP) is well-established as supportive treatment. ==Prognosis==

Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most. Stress cardiomyopathy is now a well-recognized cause of acute congestive heart failure, lethal abnormal heart rhythms, and rupture of the heart wall. ==Epidemiology==

Takotsubo syndrome represents about 2% of all patients (and 5–6% of all female patients) who are initially diagnosed with acute coronary syndrome (ACS). Recurrence rate of TTS is about 1.8% per-patient year. ==History==

, the past 30 years, specifically those with autopsies who had no internal injury, but had died of physical assault. They found that 11 of 15 had myofibrillar degeneration similar to animal stress studies. In the end, they concluded their data supported "the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart". The syndrome was first named "takotsubo" by Japanese physician Hikaru Sato, who described "tako-tsubo-like left ventricular dysfunction" in a 1990 case study. The name comes from the Japanese word takotsubo (蛸壷, "octopus trap"), because when affected by this condition, the left ventricle of the heart takes on a shape resembling the round jar used for catching lobsters and octopuses. The syndrome reached international audiences through the media in 2005 when the New England Journal of Medicine wrote about the syndrome. ==In popular culture==

• In episode 11, Season 3 ("Words and Deeds", 2007) of the TV series House, firefighter Derek suffers from this syndrome. • Appeared in episode 1 of season 1 of Astrid et Raphaëlle. • The name and title track of the 2021 album Tako Tsubo by French band L'Impératrice refers to the intense emotional stress that may provoke this syndrome. == See also ==