Answers

Short answers

1. The diagnosis is tako-tsubo cardiomyopathy, also known as left ventricular apical ballooning and "broken heart syndrome."

2. It has been traditionally associated with emotional or physical upset in postmenopausal women.

3. Patients should be treated as for acute myocardial infarction. Many develop symptoms of acute left ventricular failure and should be treated as per current guidelines (nitrates, diuretics, etc).

4. Characteristic findings are:

Chest pain or dyspnoea

Electrocardiographic changes suggestive of acute myocardial infarction or elevated cardiac troponin

Triggered by emotional or physical stress

Normal coronary angiogram

Characteristic left ventricular apical "ballooning"

Tako-tsubo cardiomyopathy
Tako-tsubo cardiomyopathy is an increasingly recognised cause of chest pain and dyspnoea in postmenopausal women that often mimics acute myocardial infarction, and should be considered in its differential diagnosis. It was first described in Japan¹ but has subsequently been identified in the USA and Europe.^{2 3 4 5} The condition is sometimes triggered by an episode of emotional stress—hence the occasionally used name "broken heart syndrome." A recent meta-analysis found an emotional stressor in 27% and a physiological stressor (asthma attack, medical examination or procedure) in 38% of patients.⁶ Initially underestimated, the literature reveals consistent prevalence rates of 1.7-2.7% in patients presenting with presumed acute myocardial infarction.^{6 7} The condition is overwhelmingly seen in women, with rates of 82-100%.^{6 8} The average age at presentation has ranged from 58 to 77 years.⁶

It is the shape of the left ventricle on imaging that gave rise to the name: a "tako-tsubo" is a traditional Japanese clay octopus trap that has the same characteristic shape as the "ballooning" ventricle, caused by reduced contractility of the mid-ventricular and apical segments and hypercontractile basal walls.¹ The most widely accepted diagnostic model is the Mayo criteria (see box).⁴

Most patients present with chest pain or dyspnoea, with rates approaching 68% and 18%, respectively. Patients can have pulmonary oedema, but reported rates have varied from zero to 46%.^{6 8} The latter series also reported the need for intra-aortic balloon pump insertion in 46% of patients—in excess of the experience in other institutions.^{4 8 9} Nevertheless, haemodynamic instability and cardiogenic shock are certainly possible complications.

The confusion with acute myocardial infarction is not only limited to the symptoms. The electrocardiogram typically shows ST segment elevation, most commonly in the anterior leads (up to 83.9% of patients). T wave changes and even pathological Q waves have been frequently seen.⁶ Cardiac enzyme changes suggest myocardial injury with increases in troponin concentrations in most patients. The troponin seems to peak earlier than in acute myocardial infarction, with highest values seen at presentation. However it is often much lower than one would expect with such extensive regional wall motion abnormalities.¹⁰ Increased concentrations of B-type natriuretic peptide (BNP) have also been seen.¹¹

The pathophysiology of the condition is as yet uncertain, although there are several theories. It is thought to be a catecholamine mediated injury in the context of low circulating oestrogen, perhaps explaining the prevalence in post-menopausal women—though it is far from exclusive to this group. Catecholamine concentrations are in excess of those seen in comparable acute myocardial infarctions¹² and animal models have shown reversibility of the changes with pretreatment with -adrenoreceptor blockade.¹³ The rat model has also shown a protective effect from oestradiol treatment in stress induced cardiomyopathy.¹⁴ Coronary artery vasospasm has been postulated—but the multivessel spasm, which would be required, has been reliably shown in very few patients.⁶ More likely is an abnormality in the microcirculation: measurement of flow rates during early coronary angiography has occasionally shown a reduction.¹⁵ The clinical picture does have similarities to the catecholamine mediated cardiomyopathy found in intracerebral and subarachnoid haemorrhage, also thought to be catecholamine mediated; however in these patients the apex is spared and it is the basal segment of the left ventricle that is hypokinetic.¹⁶ Myocarditis can also produce transient regional wall motion abnormalities but viral titres have been consistently negative in these patients.

A recent UK based series has postulated that the mechanism of injury is mediated not only through a catecholamine response, but also a left ventricular outflow tract obstruction. They found localised mid-ventricular septal thickening causing a mid-ventricular gradient, in effect dividing the ventricle into two. It is proposed that this results in distal subendocardial ischaemia, producing the characteristic changes. Dobutamine stress echocardiography reproduced the gradient, and may play some part in future diagnostic models.¹⁷

It is clearly difficult to differentiate between acute myocardial infarction and tako-tsubo cardiomyopathy and the clear consensus is that patients should initially be treated as the former.¹⁸ Currently, patients fulfilling criteria for ST elevation myocardial infarction should be referred for primary percutaneous intervention (PCI) or thrombolysis according to local guidelines. Early coronary angiography and the advent of primary PCI for acute myocardial infarction allows the identification of tako-tsubo cardiomyopathy and the possible prevention of unnecessary thrombolysis.

Pulmonary oedema due to left ventricular systolic dysfunction is often present and should be treated with supportive measures, nitrates and diuretics. β blockers have shown promise in reversing the "ballooning" of the left ventricle during simulations with dobutamine stress echocardiography and should probably be utilised.¹⁹ Angiotensin converting enzyme (ACE) inhibitors have been anecdotally shown to be effective, although no randomised prospective data yet exist.²⁰

The prognosis is good with return to normal left ventricle function in almost all patients, with recovery of normal performance.^{3 5 6 8} The rate of recurrence in the longest follow-up was low, at 11.4% over 4 years. However almost a third of patients had recurrent chest pain. Mortality was no higher than for an equivalent "normal" population.²¹

Tako-tsubo cardiomyopathy is an important differential of chest pain and indeed acute myocardial infarction, of which all acute physicians should be aware. However consideration of this uncommon diagnosis should not delay prompt reperfusion therapy. While its underlying pathophysiology remains unclear, future research may help develop more accurate diagnostic criteria and specific treatments.

Cite this as: BMJ 2008;337:a107