Takotsubo cardiomyopathy

Takotsubo cardiomyopathy, also known as transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, Gebrochenes-Herz-Syndrom, and stress cardiomyopathy is a type of non-ischaemic cardiomyopathy in which there is a sudden temporary weakening of the myocardium (the muscle of the heart). Because this weakening can be triggered by emotional stress, such as the death of a loved one, a break-up, or constant anxiety, it is also known as broken heart syndrome. Stress cardiomyopathy is a well-recognized cause of acute heart failure, lethal ventricular arrhythmias, and ventricular rupture.

Presentation
The typical presentation of someone with takotsubo cardiomyopathy is a sudden onset of congestive heart failure associated with ECG changes suggestive of 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 its name "tako tsubo", or octopus pot in Japan, where it was first described.

Evaluation of individuals with takotsubo cardiomyopathy typically includes a coronary angiogram, which will not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within 2 months. Takotsubo cardiomyopathy is more commonly seen in post-menopausal women. Often there is a history of a recent severe emotional or physical stress.

Etiology
The etiology of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed.
 * 1) Wraparound LAD: The left anterior descending artery (LAD) supplies the anterior wall of the left ventricle in the majority of patients. If this artery also wraps around the apex of the heart, it may be responsible for blood supply to the apex and the inferior wall of the heart. Some researchers have noted a correlation between takotsubo and this type of LAD. Other researchers have shown that this anatomical variant is not common enough to explain takotsubo cardiomyopathy. This theory would also not explain documented variants where the midventricular walls or base of the heart does not contract (akinesis).
 * 2) Transient Vasospasm: Some of the original researchers of takotsubo suggested that multiple simultaneous spasms of coronary arteries could cause enough loss of blood flow to cause transient stunning of the myocardium. Other researchers have shown that vasospasm is much less common than initially thought.   It has also been noted that when there are vasospasms, even in multiple arteries, that they do not correlate with the areas of myocardium that are not contracting.
 * 3) Microvascular Dysfunction: The theory gaining the most traction is that there is dysfunction of the coronary arteries at the level where they are no longer visible by coronary angiography. This could include microvascular vasospasm, however it may well also have some similarities to the diseases such as diabetes mellitus. In such disease conditions the microvascular arteries fail to provide adequate oxygen to the myocardium.
 * 4) Mid-ventricular obstruction, apical stunning It has also been suggested that a mid-ventricular wall thickening with outflow obstruction is important in the pathophysiology

It is likely that there are multiple factors at play which could include some amount of vasospasm, failure of the microvasculature, and an abnormal response to catecholamines (such as epinephrine and norepinephrine, released in response to stress).

Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after an emotional stress, while others have a preceding clinical stressor (such as an asthma attack or sudden illness). Roughly one third of patients have no preceding stressful event. A recent large case series from Europe found that takotsubo was slightly more frequent during the winter season. This may be related to two different 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 season.

Diagnosis
Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7–2.2% of patients presenting with acute coronary syndrome. While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome went previously undiagnosed before it was described in detail in the Japanese literature.

The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The ECG findings are often confused with those found during an acute anterior wall myocardial infarction. 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, dyspnea, ST-segment elevation, T-wave inversion or QT-interval prolongation on ECG. Elevation of myocardial enzymes is moderate at worst and there is absence of significant coronary artery disease.

The diagnosis is made by the pathognomonic wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or dyskinetic. This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been classically described as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and rarely local ballooning of other segments.

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.

Histology
Focal myocytolysis is reported as an origin of this cardiomyopathy. No microbiological agent has been associated so far with takotsubo cardiomyopathy. Kloner et al. reported that a pathologic change in the myocardium was not demonstrated in the stunned myocardium. Infiltration of small mononuclear cells has been documented in some cases; these pathologic findings suggest that this cardiomyopathy is a kind of inflammatory heart disease, but not a coronary heart disease. There is also a report describing histologic myocardial damage without coronary heart disease.

Treatment
The treatment of takotsubo cardiomyopathy is generally supportive in nature. Although patients with takotsubo heart disease may be hypotensive, treatment with inotropes will usually exacerbate the disease. Since the disease is due to a high catecholamine state, patients should not be given inotropes. Treatment recommendations include intra-aortic balloon pump, fluids, and negative inotropes such as beta blockers or calcium channel blockers. In many individuals, left ventricular function normalizes within 2 months. Aspirin and other heart drugs also appear to help in the treatment of this disease, even in extreme cases.

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. The patients are expecting a favorable outcome once recovering from the acute stage of the syndrome, and the long-term prognosis is excellent. Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months. Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger.

The increased awareness of this syndrome led life insurers to analyse mortality rates in general. In a March 2008 study, Jaap Spreeuw and Xu Wang of the Cass Business School observed that in the year following a loved one’s death, women were more than twice as likely to die than normal, and men more than six times as likely.

Epidemiology
Most cases occur in women (80-100%), and the average ages at onset are between 61 and 76 years.

Inspiration of economic model
The broken heart syndrome also led financial analyst David X. Li to develop the Gaussian copula models for the pricing of collateralized debt obligations where at times seemingly unrelated entities become subject to sympathetic financial defaults based on common (but at times not obvious) links.