Definition: Takotsubo cardiomyopathy is a disease of the left ventricle (LV) that mimics myocardial infarction in the absence of an acute occlusion of the coronary arteries.
The syndrome is characterized by a transient systolic dysfunction of apical or mid-ventricular segments of the LV which leads to an apical ballooning of the LV. In this typical condition the shape of the LV is comparable with the shape of a Japanese octopus trap (“takotsubo”) which gave this syndrome its name. First described in Japan, the disease occurs also in Europe or in the United States. Most commonly postmenopausal women are affected (approximately 80-100 %). A prevalence of 1.2 percent was reported for takotsubo cardiomyopathy from a large registry of patients with troponin-positive acute coronary syndrome.
In some cases also the systolic function of mid-ventricular or right-ventricular segments might be depressed (“atypical forms”).
Takotsubo cardiomyopathy is often triggered by physical or emotional stress (“Stress-induced cardiomyopathy”, “Broken Heart Syndrome”).
There might be the possibility of a genetic predisposition of affected individuals, however genetic analyses have not identified a mutation or polymorphism yet. Chronic anxiety disorders seem to be more common in patients with takotsubo cardiomyopathy.
Until now the exact pathogenesis of the disease is unclear. Presumably catecholamine excess, coronary artery spams and microvascular dysfunction are underlying causes. On the other hand dynamic mid-cavity or left ventricular outflow tract obstruction could contribute to the apical dysfunction.
Some studies demonstrated that stress conditions may cause catecholamine-induced microvascular spasms leading to myocardial stunning or catecholamine-associated myocardial toxicity. Further studies reported about higher plasma catecholamine levels in patients with takotsubo cardiomyopathy than in patients with myocardial infarction, however other studies reported about normal catecholamine levels. The catecholamine theory is supported by observations in patients with takotsubo cardiomyopathy who demonstrated multifocal coronary artery vasospasms and transient myocardial perfusion abnormalities. Further endomyocardial biopsy data demonstrated histologic signs of catecholamine toxicity.
The most common symptoms of patients with takotsubo cardiomyopathy are comparable to that of an acute myocardial infarction characterized by dyspnea, syncope, shock, or electrocardiographic abnormalities. Complications include heart failure, tachyarrhythmias, bradyarrhythmias, mitral regurgitation, cardiogenic shock, apical thrombus formation and stroke.Due to basal LV hyperkinesis also LV outflow tract obstruction (LVOTO) might be induced contributing to the development of a cardiogenic shock.
Specific diagnostic findings are:
- ECG: Electrocardiographic abnormalities are common. ST segment elevation is most common in the anterior precordial leads. Further deep T wave inversion with QT interval prolongation, abnormal Q waves and non-specific abnormalities can be found. However, sometimes the ECG is normal at presentation.
- Cardiac biomarkers: In most studies cardiac troponins and creatine kinase MB elevations could be observed in patients with takotsubo cardiomyopathy. However, elevations are typically only mild.
- Echocardiography / Left ventriculography: Most patients demonstrate the typical apical ballooning with akinesis or hypokinesis of the LV apex. Commonly LV ejection fraction (EF) is reduced with an LV-EF between 20 to 49 %. Sometimes LVOT obstruction and a systolic anterior movement of the anterior mitral leaflet can be observed. Echocardiography can be used to detect a thrombus of the left or right ventricle.
- Cardiac magnetic resonance imaging (CMRI): CMRI demonstrates typically wall motion abnormalities of mid and apical LV walls without late gadolinium enhancement (LGE). Therefore LGE is helpful in differentiating takotsubo cardiomyopathy from myocarditis, which often shows patchy LGE. However, patients regularly show focal myocardial edema on CMRI corresponding to the areas of wall motion abnormality.
- Coronary angiography: Patients with takotsubo cardiomyopathy have regularly no or only a mild to moderate coronary artery disease. Some studies suggest the concept of a transient occlusion of a coronary artery in takotsubo cardiomyopathy which should lead to an apical stunning and after thrombus lysis to an improvement during follow-up. However, other studies reported about a low prevalence of such transient occlusions in patients with takotsubo cardiomyopathy.
- Differential diagnosis: Some other conditions like cardiac syndrome X, variant (Prinzmetal's) angina, myocarditis, or cocaine abuse can be associated with changes in ECG patterns without coronary artery disease. Also in patients with pheochromocytoma or acute brain injury global or focal myocardial dysfunction can be observed.
- Involvement of the right ventricle: Sometimes also a right ventricular involvement can be observed in patients with takotsubo cardiomyopathy. In one study with 34 patients 9 individuals had an affection of the right ventricle, which disappeared in 8 patients during the next year.
Due to the fact that takotsubo cardiomyopathy is a transient disorder conservative treatment - including physical and emotional stress avoidance – is the therapy of choice.
Although there are no controlled data regarding the optimal medical treatment, patients should be treated with standard regimes for LV systolic dysfunction including the use of ACE inhibitors, beta blockers and diuretics for treatment of volume overload. Aspirin should be given in case of a coexisting coronary atherosclerosis. There are only some weak recommendations for the duration of treatment. Most commonly treatment should be continued until LV function recovers. Some experts recommend continuing an adrenergic blockade with beta-blockers in order to avoid disease recurrence. In patients with cardiogenic shock LVOT obstruction should be excluded by echocardiography.
Hypotensive patients can be treated by inotropes like dobutamine or dopamine, however the influence of sympathomimetics remains unclear, particularly because the condition is presumably caused by a catecholamine excess. Patients with LVOT obstruction should not be treated by inotropic agents because outflow tract obstruction can be worsened. Here are beta blockers the therapy of choice. Alpha agonists may be added to treat LVOT obstruction. Patients with severe hypotension or shock can be treated by intra-aortic balloon counterpulsation (IABP).
Echocardiography or alternatively CMRI should be used to screen for an intraventricular thombus. Data regarding anticoagulation therapy in order to prevent thromboembolism are sparse. Regularly anticoagulation therapy is recommended for approximately three months if an intraventricular thrombus is detected or for patients with severe left ventricular dysfunction. If LV function has recovered anticoagulation therapy can be stopped earlier.
The mortality rate of takotsubo cardiomyopathy lies between 0 to 8 percent. LV function recovers approximately within one to four weeks [18, 35]. In a follow-up study with 100 individuals 10 patients had recurrence of takotsubo cardiomyopathy within a mean follow-up of approximately four years.
Takotsubo cardiomyopathy is a disease characterized by transient LV dysfunction without an underlying relevant coronary artery disease.
Takotsubo cardiomyopathy is typically triggered by emotional or physical stress. However, a triggering event is not always present.
Pathogenic mechanisms include catecholamine excess, coronary artery spasm, and microvascular dysfunction.
Clinical presentation includes oftentimes ECG abnormalities and elevated cardiac biomarkers. Typical symptoms are chest pain and dyspnea.
Diagnosis is based on transient regional wall motion abnormalities without an underlying relevant coronary artery disease or an acute plaque rupture, presence of new ECG abnormalities or modest troponin elevation. A pheochromocytoma or myocarditis should be excluded.
Complications of takotsubo cardiomyopathy are acute heart failure, tachyarrhythmias, bradyarrhythmias, cardiogenic shock, and transient LVOT obstruction.
The mortality rate is approximately 0-8 percent. LV function recovers typically within one to four weeks.
The basic therapy of takotsubo cardiomyopathy is largely supportive. The short-term use of standard medications for heart failure due to systolic dysfunction is recommended by experts.
- ↑ Kurowski V, Kaiser A, von Hof K, et al. Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest 2007; 132:809.
- ↑ Pison L, De Vusser P, Mullens W. Apical ballooning in relatives. Heart 2004; 90:e67.
- ↑ Kumar G, Holmes DR Jr, Prasad A. "Familial" apical ballooning syndrome (Takotsubo cardiomyopathy). Int J Cardiol 2010; 144:444.
- ↑ Handy AD, Prasad A, Olson TM. Investigating genetic variation of adrenergic receptors in familial stress cardiomyopathy (apical ballooning syndrome). J Cardiol 2009; 54:516.
- ↑ Sharkey SW, Maron BJ, Nelson P, et al. Adrenergic receptor polymorphisms in patients with stress (tako-tsubo) cardiomyopathy. J Cardiol 2009; 53:53.
- ↑ Summers MR, Lennon RJ, Prasad A. Pre-morbid psychiatric and cardiovascular diseases in apical ballooning syndrome (tako-tsubo/stress-induced cardiomyopathy): potential pre-disposing factors? J Am Coll Cardiol 2010; 55:700.
- ↑ Gianni M, Dentali F, Grandi AM, et al. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J 2006; 27:1523.
- ↑ Nef HM, Möllmann H, Kostin S, et al. Tako-Tsubo cardiomyopathy: intraindividual structural analysis in the acute phase and after functional recovery. Eur Heart J 2007; 28:2456.
- ↑ Madhavan M, Borlaug BA, Lerman A, et al. Stress hormone and circulating biomarker profile of apical ballooning syndrome (Takotsubo cardiomyopathy): insights into the clinical significance of B-type natriuretic peptide and troponin levels. Heart 2009; 95:1436.
- ↑ Tsuchihashi K, Ueshima K, Uchida T, et al. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan. J Am Coll Cardiol 2001; 38:11.
- ↑ Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 2005; 111:472.
- ↑ Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 2002; 143:448.
- ↑ Ito K, Sugihara H, Katoh S, et al. Assessment of Takotsubo (ampulla) cardiomyopathy using 99mTc-tetrofosmin myocardial SPECT--comparison with acute coronary syndrome. Ann Nucl Med 2003; 17:115.
- ↑ Abe Y, Kondo M, Matsuoka R, et al. Assessment of clinical features in transient left ventricular apical ballooning. J Am Coll Cardiol 2003; 41:737.
- ↑ Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352:539.
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- ↑ Fineschi V, Silver MD, Karch SB, et al. Myocardial disarray: an architectural disorganization linked with adrenergic stress? Int J Cardiol 2005; 99:277.
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- ↑ 19.0 19.1 Desmet WJ, Adriaenssens BF, Dens JA. Apical ballooning of the left ventricle: first series in white patients. Heart 2003; 89:1027.
- ↑ 20.0 20.1 Sharkey SW, Windenburg DC, Lesser JR, et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol 2010; 55:333.
- ↑ 21.0 21.1 Barrera-Ramirez CF, Jimenez-Mazuecos JM, Alfonso F. Apical thrombus associated with left ventricular apical ballooning. Heart 2003; 89:927.
- ↑ 22.0 22.1 22.2 Villareal RP, Achari A, Wilansky S, Wilson JM. Anteroapical stunning and left ventricular outflow tract obstruction. Mayo Clin Proc 2001; 76:79.
- ↑ 23.0 23.1 Sharkey SW, Lesser JR, Menon M, et al. Spectrum and significance of electrocardiographic patterns, troponin levels, and thrombolysis in myocardial infarction frame count in patients with stress (tako-tsubo) cardiomyopathy and comparison to those in patients with ST-elevation anterior wall myocardial infarction. Am J Cardiol 2008; 101:1723.
- ↑ Dib C, Asirvatham S, Elesber A, et al. Clinical correlates and prognostic significance of electrocardiographic abnormalities in apical ballooning syndrome (Takotsubo/stress-induced cardiomyopathy). Am Heart J 2009; 157:933.
- ↑ Ogura R, Hiasa Y, Takahashi T, et al. Specific findings of the standard 12-lead ECG in patients with 'Takotsubo' cardiomyopathy: comparison with the findings of acute anterior myocardial infarction. Circ J 2003; 67:687.
- ↑ Eitel I, Behrendt F, Schindler K, et al. Differential diagnosis of suspected apical ballooning syndrome using contrast-enhanced magnetic resonance imaging. Eur Heart J 2008; 29:2651.
- ↑ Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 2011; 306:277.
- ↑ Ibanez B, Navarro F, Cordoba M, et al. Tako-tsubo transient left ventricular apical ballooning: is intravascular ultrasound the key to resolve the enigma? Heart 2005; 91:102.
- ↑ Hoyt J, Lerman A, Lennon RJ, et al. Left anterior descending artery length and coronary atherosclerosis in apical ballooning syndrome (Takotsubo/stress induced cardiomyopathy). Int J Cardiol 2010; 145:112.
- ↑ Kassim TA, Clarke DD, Mai VQ, et al. Catecholamine-induced cardiomyopathy. Endocr Pract 2008; 14:1137.
- ↑ Ako J, Sudhir K, Farouque HM, et al. Transient left ventricular dysfunction under severe stress: brain-heart relationship revisited. Am J Med 2006; 119:10.
- ↑ Elesber AA, Prasad A, Bybee KA, et al. Transient cardiac apical ballooning syndrome: prevalence and clinical implications of right ventricular involvement. J Am Coll Cardiol 2006; 47:1082.
- ↑ 33.0 33.1 Haghi D, Athanasiadis A, Papavassiliu T, et al. Right ventricular involvement in Takotsubo cardiomyopathy. Eur Heart J 2006; 27:2433.
- ↑ Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 2008; 155:408.
- ↑ Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation 2008; 118:2754.
- ↑ Elesber AA, Prasad A, Lennon RJ, et al. Four-year recurrence rate and prognosis of the apical ballooning syndrome. J Am Coll Cardiol 2007; 50:448.