Takotsubo Cardiomyopathy

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Diagnosis and reasoning

This elderly lady has presented with acute chest discomfort and dyspnea following a stressful event; this should be considered an acute coronary syndrome (ACS) until proven otherwise. Her ECG shows ST-segment elevations in the left and anterior leads, suggesting at an anterior ST-segment elevation myocardial infarction (STEMI); the positive cardiac troponins are further supportive in this regard. As she has presented relatively early, the next step should be urgent angiography (possibly as a preclude to revascularization and stenting); a bedside echocardiogram may also be considered while facilities are being prepared. The echocardiogram shows regional systolic dysfunction of the left ventricle (LV), predominantly affecting the apex and middle segments; while not typical for a STEMI, this is still compatible with the clinical diagnosis. However, angiography reveals an unexpected finding: coronary arteries which are virtually pristine. This is not an ACS! Furthermore, ventriculography reveals apical ballooning with hyperkinesis of the basal segments and hypokinesis of the apical segments. This is almost pathognomonic of Takotsubo cardiomyopathy (also known as transient apical ballooning syndrome or stress induced cardiomyopathy), one of the few reversible cardiomyopathies. Thus, her management should mainly be supportive in nature. Angiotensin-converting enzyme (ACE)-inhibitor and beta-blocker therapy will aid with the LV systolic dysfunction. Note that intropes are not currently indicated, as she is hemodynamically stable. Thrombolytic administration is not only useless, but potentially harmful.


Discussion

Takotsubo cardiomyopathy is a reversible cardiomyopathy triggered by profound psychological or physical stress; it is named after the pots Japanese fishermen use to trap octopuses (i.e. a narrow neck and broad base with a globular form), as the LV assumes a similar shape during ventricular systole. The condition shows a marked female preponderance; the vast majority of these patients are postmenopausal. Note however, that it can occur in younger women, as well as in men. Importantly, it has been estimated that between 1.5% to 2.2% of patients diagnosed with acute myocardial infarction may actually have had Takotsubo cardiomyopathy. An acute emotional stressor (such as an accident, quarrel, or death) or a physiological stressor (such as acute medical conditions or surgery) is present in most of these patients, with a clear temporal relationship between the stressor and the onset of symptoms. However, in upto 20% of individuals, no such trigger can be identified - hence, its absence does not exclude the diagnosis. While the exact pathophysiology of Takotsubo cardiomyopathy is still unclear, several theories have been suggested. The most popular of these postulates that myocardial stunning occurs due to an excess of catecholamines. Other theories include microvascular vasospasm and/or dysfunction; and multiple epicardial coronary artery vasospasms with resulting ischemia. The clinical presentation mimics that of an ACS, with chest pain/discomfort and dyspnea being the two most common presenting symptoms. Most patients have an abnormal ECG; the most common pattern is ST-segment elevation in the precordial leads, followed by diffuse T-wave inversions. Cardiac biomarkers (i.e. troponins and creatine kinase) are usually only minimally elevated (i.e. considerably less than those observed in a ST-segment myocardial infarction), and are disproportionately low when compared to the extensive acute regional wall motion abnormalities. Biomarker levels are maximal at the time of presentation, and usually do not follow the slow rise and fall kinetics observed in an ACS. Angiography typically reveals normal coronary arteries or occasional mild irregularities inconsistent with the observed wall motion abnormality; contrast enhanced left ventriculography shows apical and mid-ventricular akinesis or dyskinesis with a normal or hypercontractile base. Echocardiography confirms the dysfunctional contractile pattern, with the initial ejection fraction typically ranging from 20% to 40%; over a period of days to weeks the ventricular dysfunction rapidly reverses, and the ejection fraction normalizes to between 60% to 75% in most patients. Note that atypical forms of Takotsubo syndrome have been identified. Right-ventricular involvement occurs in approximately 25% of patients, while other forms include transient midventricular ballooning with basal and apical hypercontraction, and basal and midventricular akinesia with or without apical hyperkinesia. The clinical features of the atypical forms are the same as that of the classical disease; however, right ventricular and biventricular involvement is associated with worse myocardial dysfunction. Several sets of criteria have been proposed for diagnosis of the condition, including the Mayo criteria, Abe and Kondo criteria, Segovia Cubero criteria, and Kawai criteria. Of these, the Mayo criteria is the most widely used; key elements include: 1. Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid segments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always present. 2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture. 3. New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin. 4. Absence of pheochromocytoma and myocarditis. As Takotsubo cardiomyopathy is a transient disorder, the treatment is mainly supportive and should be tailored to the patient's overall clinical and hemodynamic status. If patients are hemodynamically stable, it is reasonable to treat them on the lines of left ventricular systolic dysfunction with beta-blockers, ACE inhibitors, and if pulmonary edema develops, diuretics. Patients who present with shock, and do not have left ventricular outflow tract obstruction can be treated with cautious use of inotropic agents such as dobutamine and dopamine; those with left ventricular outlet obstruction can be given a trial of beta-blockers in an attempt to increase LV end-diastolic volume by increasing duration of diastolic ventricular filling time and by reducing overall contractility. Those who cannot tolerate beta-blockers or do not respond may benefit from administration of phenylephrine, a pure alpha-adrenergic agonist which may reduce the transient intraventricular gradient by increasing afterload, thereby improving overall hemodynamics. If unresponsive to any of the above treatments, an intra-aortic balloon pump to maintain circulatory dynamics should be considered. Note that there is no current data on the duration of therapy; the general consensus is that it may be stopped once systolic function has recovered, unless there are comorbidities. The short term and long term prognosis of these patients is extremely favorable; with proper medical and supportive therapy in-hospital mortality rates range <1%; death is more common in the setting of outflow obstruction. However, despite this relatively benign prognosis, more serious complications (cardiogenic shock and ventricular fibrillation) have been reported in as many as 4.2% and 1.5% of patients respectively. Recurrence is uncommon; the 4-year recurrence rate has been reported as 11.4%, although there was no significant difference in survival compared to an age and gender matched population over the same duration,


Take home messages

  1. Takotsubo cardiomyopathy is one of the few reversible cardiomyopathies.
  2. In the vast majority of patients, an acute stressor can be identified.
  3. A high index of suspicion is essential for the diagnosis; while angiography is confirmatory, the diagnosis can be suspected upon echocardiography.
  4. Management is mainly supportive; with proper care, patients have an excellent prognosis.

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