Cardiomyopathy, Takotsubo Syndrome (Transient Apical Ballooning, Stress-Induced Cardiomyopathy, Gebrochenes-Herz Syndrome)

Article Author:
Daniel Brito
Article Editor:
Michael Ibrahim
Updated:
10/27/2018 12:31:27 PM
PubMed Link:
Cardiomyopathy, Takotsubo Syndrome (Transient Apical Ballooning, Stress-Induced Cardiomyopathy, Gebrochenes-Herz Syndrome)

Introduction

Takotsubo cardiomyopathy is also known as Gebrochenes-Herz syndrome, transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, stress cardiomyopathy, and broken-heart syndrome. This is a form of nonischemic cardiomyopathy.

Takotsubo cardiomyopathy is a syndrome characterized by transient regional systolic dysfunction of the left ventricle mimicking acute myocardial infarction but has a minimal release of cardiac enzymes. There is an absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture. In most cases of Takotsubo cardiomyopathy, the regional wall motion abnormality extends beyond the territory perfused by a single epicardial coronary artery.

The term Takotsubo is a Japanese name for an octopus trap. It has a shape that is similar to the systolic apical ballooning appearance of the left ventricle.

Etiology

The cause of Takotsubo cardiomyopathy is not fully understood. There are several mechanisms hypothesized as possible etiologies of Takotsubo cardiomyopathy.

Epidemiology

The real incidence of Takotsubo cardiomyopathy is uncertain.

In the United States, several studies have estimated that it may account for approximately 1% to 2% of patients presenting with increased troponin with concern for acute coronary syndrome. A similar prevalence was found in a German and French study.

One registry of 3265 patients with troponin positive acute coronary syndrome, reported the prevalence of 1.2% of Takotsubo cardiomyopathy. Also in a systemic review of suspected acute coronary syndrome or ST-elevation myocardial infarction, Takotsubo was reported in 1.7 to 2.2 percent of cases.

A strong predilection for female gender and postmenopausal women has been one of the hallmarks. There are some exceptions, and there is a higher proportion of premenopausal females with an apical sparing variant of Takotsubo cardiomyopathy. Mean age range is 58 to 75 years. The disease occurs in all races.

Pathophysiology

Takotsubo cardiomyopathy pathogenesis is not well understood. Postulated mechanisms of Takotsubo cardiomyopathy includes catecholamine excess, coronary artery spasm, and microvascular dysfunction.

The role of catecholamines is suggested because the disorder is frequently associated with physical or emotional stress. This disorder may be caused by diffuse catecholamine-induced microvascular spasm or dysfunction, resulting in myocardial stunning, or by direct catecholamine-associated myocardial toxicity. Plasma catecholamines levels are significantly higher in patients with stress cardiomyopathy as compared to those with myocardial infarction. However, elevation of blood catecholamine levels is not uniformly present in all studies.

The role of coronary artery disease or dysfunction is also a potential mechanism of Takotsubo cardiomyopathy. Takotsubo cardiomyopathy presentation is similar to an acute myocardial infarction; however, coronary artery angiography usually shows no obstructive disease. In some patients, there is coronary artery spasm with acetylcholine provocation. 

History and Physical

Takotsubo cardiomyopathy presentation is similar to an acute coronary syndrome (ST-elevation myocardial infarction, non-ST elevation myocardial infarction, or unstable angina).

This disorder is frequently triggered by intense emotional or physical stress, for example, the unexpected death of family member, domestic abuse, significant confrontation, medical diagnosis, natural disaster, and/or financial loss.

In the International Takotsubo Registry study, most common symptoms are chest pain, dyspnea, and syncope. Some patients may present with symptoms and signs of heart failure, tachyarrhythmias, bradyarrhythmias, sudden cardiac arrest, or severe mitral regurgitation.

On auscultation, there may be a late-peaking systolic murmur due to left ventricular outflow tract obstruction.

There also may be symptoms and signs of transient ischemic attack or stroke like presentation due to embolization from apical thrombus.

Approximately, 10% of patients with stress cardiomyopathy develop cardiogenic shock.

Evaluation

The diagnosis of stress cardiomyopathy should be suspected in adults (particularly postmenopausal women) who present with a suspected acute coronary particularly when the clinical manifestations and electrocardiographic abnormalities are out of proportion to the degree of elevation in cardiac biomarkers. It is important to emphasize that because of the indistinguishable features with the acute coronary disease, Takotsubo cardiomyopathy is a diagnosis of exclusion which can only be made after coronary angiography.

The following are Mayo Clinic diagnostic criteria for identification to stress cardiomyopathy. All are required for the diagnosis:

  1. Transient hypokinesis, akinesis, or dyskinesis in the left ventricular mid segments with or without apical involvement; regional wall motion abnormalities that extend beyond.
  2. A single epicardial vascular distribution; and frequently, but not always, a stressful trigger.
  3. The absence of obstructive coronary disease or angiographic evidence of acute plaque rupture.
  4. New ECG abnormalities (ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin.
  5. The absence of pheochromocytoma and myocarditis.

Electrocardiographic findings usually are ST-segment elevation (more common) or depression or repolarization abnormalities. A couple of days after presentation, ST-segment abnormalities revert and T wave inversion might be seen with giant and symmetrical T waves, generally in the precordial leads. In the Takotsubo Registry study, ST elevation is present in 43.7% of patients. Most commonly, there is ST elevation in the anterior precordial leads similar to acute ST-elevation myocardial infarction. ST-segment depression is present in 7.7% of patients. Other findings include QT interval prolongation, T wave inversion, abnormal Q waves, and non-specific ST abnormalities.

Cardiac biomarkers as troponins and CK-MB show mild elevation. According to the International, Takotsubo Registry study, the median initial troponin 7.7 times the upper limit of normal.

Levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP are elevated in most patients with stress cardiomyopathy and exceeded those seen in matched cohort of patients with acute coronary syndrome (median 5.89 versus 2.91 times the upper limit of normal).

Transthoracic echocardiography demonstrates the wall motion abnormalities classified as:

  • Apical type (typical): there is a systolic apical ballooning of the left ventricle, with depressed mid and apical segments, and also hyperkinesis of the basal walls. Found in around 80% of patient in the International Takotsubo Registry study.
  • Atypical variants: Mid-ventricular type hypokinesis (14.6%), basal type hypokinesis (2.2%), focal type hypokinesis (most commonly the anterolateral segment) (1.5%) and global hypokinesis.

Most patients with stress cardiomyopathy have reduced overall left ventricular systolic function, and right ventricular dysfunction has been reported too.

Cardiovascular magnetic resonance may be helpful in the diagnosis and evaluation of stress cardiomyopathy, particularly when the echocardiogram is suboptimal, or there is coexistent coronary artery disease. Cardiovascular magnetic resonance may assist in the differential diagnosis, delineate the full extent of ventricular abnormalities, and identify associated complications.

Radionuclide myocardial perfusion imaging is not indicated in most patients presenting with Takotsubo cardiomyopathy since most the common presentation is acute coronary syndrome requiring cardiac catheterization. In a low to intermediate risk non-ST elevation acute coronary syndrome, radionuclide myocardial perfusion imaging may be helpful.

Cardiac catheterization is an invasive procedure of choice when Takotsubo cardiomyopathy present as ST- elevation acute coronary syndrome or troponin positive acute coronary syndrome. Coronary angiography will show normal coronary anatomy or mild to moderate coronary atherosclerosis.

Treatment / Management

Since initial presentation of Takotsubo cardiomyopathy is similar to acute coronary syndrome, initial treatment involves aspirin, beta blocker, ACE inhibitor, a lipid-lowering agent, and coronary angiography to rule out obstructive coronary artery disease. 

Takotsubo cardiomyopathy is a temporary condition, and hence the goals of treatment are usually conservative and supportive care. The therapy is guided by the patient’s clinical presentation and hemodynamic status.

In stable patients, treatment modalities include cardioselective beta-blockers and ACE inhibitor for a short period around 3-6 months, with serial imaging studies to determine wall motion abnormalities and ventricular ejection fraction to determine progression or improvement.

Anticoagulation is usually reserved for those with documented ventricular thrombus or evidence of embolic events; that occur in 5% of patient with Takotsubo cardiomyopathy.

In a patient with more unstable hemodynamics, or those who present in cardiogenic shock, and in the absence of left ventricular outflow obstruction, should be treated with inotropes. Alternatively, patients may derive further benefit from mechanical hemodynamic support with intra-aortic balloon pump or rarely, left ventricular assist devices. If left ventricular outflow obstruction is present with cardiogenic shock, inotropes should be avoided, and phenylephrine is the pressor agent of choice often combined with beta-blocker agents.

Pearls and Other Issues

Takotsubo cardiomyopathy has an excellent prognosis, with full and early recovery in almost all patients with proper recognition and management. The majority of patients have normalization of left ventricular ejection fraction within a week and all patients by four to eight weeks. The reported in-hospital mortality is low around 0% to 8%. Recurrence is unusual. Long-term survival is similar to the general population.