|Year : 2017 | Volume
| Issue : 2 | Page : 119-125
Takotsubo cardiomyopathy: Lessons learned
Ritesh Vishwakarma, Shantanu Sengupta
Department of Cardiology, Sengupta Hospital and Research Institute, Nagpur, Maharashtra, India
|Date of Web Publication||28-Aug-2017|
Sengupta Hospital and Research Institute, Ravinagar Square, Nagpur, Maharashtra
Source of Support: None, Conflict of Interest: None
Takotsubo cardiomyopathy presents as acute heart failure and mimics acute coronary syndrome. It is characterized by transient left ventricular dysfunction in the absence of occlusive coronary disease. Prognosis is generally good with complete recovery of the left ventricle in several weeks. The etiology is unknown and therapy just symptomatic. Death has been described but is rare. This present review gives insights of this important clinical entity.
Keywords: Apical ballooning syndrome, broken heart syndrome, echocardiography, stress-induced cardiomyopathy, takotsubo cardiomyopathy
|How to cite this article:|
Vishwakarma R, Sengupta S. Takotsubo cardiomyopathy: Lessons learned. J Indian Acad Echocardiogr Cardiovasc Imaging 2017;1:119-25
|How to cite this URL:|
Vishwakarma R, Sengupta S. Takotsubo cardiomyopathy: Lessons learned. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2017 [cited 2023 Jun 10];1:119-25. Available from: https://jiaecho.org/text.asp?2017/1/2/119/213679
| Introduction|| |
The name of the syndrome was sealed up on the basis of similarities between left ventricular (LV) systolic appearance (apical ballooning with narrow neck and wide base) in most common and typical form of this disorder and the shape of a Japanese octopus trap.
Takotsubo cardiomyopathy (TCM) (also called apical ballooning syndrome, broken heart syndrome, and stress-induced cardiomyopathy) is a syndrome characterized by transient regional systolic dysfunction of the LV, mimicking myocardial infarction (MI), but in the absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture.,,,,,,,,,,,,,,, In most cases of TCM, the regional wall motion abnormality extends beyond the area perfused by a single epicardial coronary artery.
| Epidemiology|| |
TCM was first described in 1990 in Japan.,,,,,,, It has been reported in approximately 1%–2% of patients presenting with troponin-positive suspected acute coronary syndrome (ACS) or suspected ST-elevation MI.,, The prevalence of 1.2% was reported from a registry of 3265 patients with troponin-positive ACS. Similarly, TCM accounted for 1.7–2.2 of cases presenting with suspected ACS or ST-elevation infarction in a systematic review.
TCM may appear in the patients with the age range extends from the first to the ninth decade, and 90% of patients are usually female and most commonly postmenopausal with the median age 67 ± 13 years,,,,,, whereas men account for <10% of cases. TCM's incidence is unknown among individuals exposed to physical or emotional stress. A prospective study of 92 patients admitted to a medical intensive care unit with a noncardiac diagnosis and no prior history of cardiac disease found that 26 patients (28%) had LV apical ballooning consistent with TCM. LV function normalized in twenty of these patients at a mean of 7 days. As per the data, the incidence of TCM is consistently increasing in last years [Figure 1].
|Figure 1: MEDLINE search showing rise in incidence of SCM with different names in last years|
Click here to view
| Pathophysiology|| |
The actual pathophysiology of this disorder is not well understood. Why this disorder affects postmenopausal women disproportionately or why the LV mid-cavity and apex are predominantly affected is not known. Studies comparing LV systolic and diastolic function in patients with TCM with function in patients with acute MI have reached differing conclusions., Initial systolic function may be similar or worse with TCM compared with acute MI, whereas diastolic function may be similar or better with TCM. Postulated mechanisms include catecholamine excess,, coronary artery spasm, and microvascular dysfunction. Alternatively, there may be dynamic mid-cavity or LV outflow tract obstruction that may contribute to apical dysfunction.
A number of features of TCM, including its association with physical or emotional stress,,,,,,,,, suggesting that the disorder may be caused by diffuse catecholamine-induced microvascular spasm or dysfunction, which results in myocardial stunning, or by direct catecholamine-associated myocardial toxicity. In some patients with TCM, the only apparent stressor is exposure to catecholamine or beta-agonist drugs in routine clinical doses. Some studies support the possible pathogenic role for catecholamines where plasma catecholamines were measured at the time of presentation., Combined results revealed that plasma norepinephrine levels were elevated 74% of patients. The magnitude of catecholamine excess associated with this disorder was explained in a report that measured plasma catecholamine levels in 13 patients with TCM and seven patients with a Killip class III MI. Plasma catecholamines were significantly higher in the patients with TCM in comparison with those with MI: epinephrine (1264 vs. 376 pg/mL) and norepinephrine (2284 vs. 1100 pg/mL)., Further support for the catecholamine hypothesis was provided by a study where patients were exposed to catecholamine or beta-agonist drug for a therapeutic purpose and observed that patients had TCM., Additional support got from the studies where similar reversible cardiomyopathy of LV with global or focal dysfunction in patients with pheochromocytoma, and in patients with acute brain injury where there is catecholamine excess in blood.
Coronary artery disease or dysfunction
Although the clinical presentation mimics an acute MI, coronary angiography typically shows no obstructive lesions,, and only a minority of patients show stimulated coronary spasm with acetylcholine.,, The occasional finding of multifocal coronary vasospasm on coronary angiography,, and transient myocardial perfusion abnormalities that resolve with improvement in the myopathy,, and the presence of abnormal thrombolysis in myocardial infarction frame counts on angiography supports the hypothesis of coronary vascular dysfunction, which may be catecholamine-induced. A potential role for plaque rupture and thrombosis with spontaneous thrombolysis has not been established and the results of intravascular ultrasound studies are mixed.,,
There are some limited reports of familial cases which raise the possibility of a genetic predisposition.,,, Small studies of patients with TCM have found genetic heterogenecity and suggest a possible polygenic basis.,,, Patients with psychiatric or neurologic disorders may be predisposed to develop TCM.,,,,,,,,,, In patients with TCM, 55.8% of patients had an acute, former, or chronic psychiatric (e.g., affective or anxiety disorder) or neurologic disorder (e.g., seizure or headache disorder) in comparison with 25.7% of patients with ACS in the International Takotsubo Registry study.,,,,,,
Other less common factors include cocaine use, opiate withdrawal, dobutamine stress testing,, lightning strike, ergonovine injection, and thyrotoxicosis.
| Symptoms, Signs, and Features|| |
The most common presenting symptom is acute substernal chest pain (70%–90%) but some patients may have less common symptoms such as dyspnea (20%) and pulmonary edema. Rarely, there may be cardiac arrest, cardiogenic shock, and serious ventricular arrhythmias.,, Very rarely, patients may present with nonspecific symptoms such as syncope, weakness, cough, and fever. An emotional, psychological, or physical stressor (or a combination) is typical, although not always present. Late-peaking systolic murmur may be heard due to LV outflow tract obstruction, induced by LV basal hypercontractility. It may contribute to the development of shock and cause severe mitral regurgitation. Symptoms and signs of transient ischemic attack or stroke may develop (likely due to embolization from apical thrombus).,
Electrocardiogram (ECG) abnormalities are common in TCM.
- ST segment elevation occurs most commonly in the anterior precordial leads often mimicking that in acute ST-elevation MI
- ST depression, QT interval prolongation, T-wave inversion, abnormal Q waves, and nonspecific abnormalities are seen less commonly.,,,
Serum cardiac troponin levels are elevated while creatine kinase levels are generally normal or mildly elevated in the patients of TCM., The normal-to-mild elevation in creatine kinase contrasts with the substantial (approximately 10%) risk of severe hemodynamic compromise.
Brain natriuretic peptide (BNP) or N-terminal pro-BNP levels are elevated in most patients (83%) of TCM., BNP levels in a matched cohort of patients with TCM exceeded those seen in matched cohort of patients with ACS (median 5.89 vs. 2.91 times the upper limit of normal).
Radionuclide myocardial perfusion imaging
Radionuclide myocardial perfusion imaging may reveal transient perfusion abnormalities in the LV apex in patients with TCM., However it is not routinely in patients with suspected TCM since most have high risk features of acute coronary syndrome and always need a coronary angiogram.
| Diagnosis|| |
Approach to diagnosis
Adults (particularly postmenopausal women) who present with a suspected ACS (chest pain or dyspnea combined with electrocardiographic changes and/or cardiac troponin elevation), possibility of TCM should be suspected in such patients, particularly when the clinical manifestations, extend of wall motion abnormalities of LV and electrocardiographic abnormalities are out of proportion to the degree of elevation in cardiac biomarkers. A physical or emotional trigger is often but not always present in such patients.
Mayo Clinic diagnostic criteria for TCM is used for diagnosis, all four of which are required for the diagnosis:,
- Transient LV systolic dysfunction (hypokinesia, akinesia, or dyskinesia). There are typical regional wall motion abnormalities extending beyond a single epicardial coronary distribution; rare exceptions are the focal (within one coronary distribution) and the global type
- Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture. If coronary disease is found, the diagnosis of TCM can still be made if the wall motion abnormalities are not in the distribution of the coronary disease. This exception is made since some patients with TCM have concurrent coronary disease (15.3% in the International Takotsubo Registry)
- New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin
- Absence of pheochromocytoma or myocarditis.
Thus, in general, coronary angiography, serial assessment of LV systolic function (initial assessment generally by ventriculography or echocardiography with subsequent assessment generally by echocardiography), an ECG, and cardiac troponin level are required to diagnose TCM. Differentiation from pheochromocytoma and myocarditis additionally required.
Typically normal coronaries or in some cases mild-to-moderate coronary atherosclerosis are demonstrated. In some cases with TCM, obstructive coronary artery disease is seen which likely reflects the prevalence of coronary artery disease in the population at risk for TCM.,
Left ventricular wall motion abnormalities
LV dysfunction is identified by echocardiography or left ventriculography, which reveals regional wall motion abnormalities (hypokinesis, akinesis, or dyskinesis) in one of the characteristic patterns.,,,,,,,
- Apical type – in the typical form of this disorder, there is systolic apical ballooning of the LV with hypercontractile basal walls [Figure 2] and [Figure 3]
- Less common (atypical) variants:
- Mid-ventricular type – In the second most common type, ventricular hypokinesis is restricted to the mid-ventricle with relative sparing of the apex,
- Basal type – Hypokinesia of the base with sparing of the mid-ventricle and apex (reverse or inverted takotsubo) [Figure 4]
- Focal type – A rare focal variant is characterized by dysfunction of an isolated segment (most commonly the anterolateral segment) of the LV
- Global type – Rarely, patients have global hypokinesis.
|Figure 2: Systolic apex balloon-like dilation on left ventriculography (a) and normal diastolic dilation (b). (a) Systole; (b) diastole|
Click here to view
|Figure 3: Apical ballooning in end-systolic frame in A4CV and ALAX views (arrows)|
Click here to view
|Figure 4: A4CV and A2CV after recovery. Note absence of apical ballooning and decrease in end-systolic size|
Click here to view
In most patients with TCM, there is reduced overall LV systolic function.,,, Although reports of TCM have focused on transient dysfunction of the LV, there is evidence that about one-third of cases involve both right and LVs.,,,
Additional tests to exclude other conditions
When the diagnosis of TCM is uncertain, additional testing is suggested such as cardiovascular magnetic resonance (CMR) showing late gadolinium enhancement assist in the differential diagnosis, delineate the full extent of ventricular abnormalities (LV and right ventricle), and identify associated complications. Positron emission tomography – identify a discrepancy between normal perfusion and reduced glucose utilization in dysfunction regions, known as an “inverse flow-metabolism mismatch.” CMR is helpful in detecting myocardial edema which is classically seen in this condition. Role of computed tomography scan is for used as an alternative to coronary angiography to confirm coronary patency. There is lot of ongoing work focusing on molecular imaging in patients with severe form of takotsubo and with chances of recurrence.
| Takotsubo in Children and Young|| |
Mostly this entity is seen in adults, but recently few cases have been reported to have its occurrence in children and younger age groups. Hernandez has reported that around 12 cases have been published worldwide in children and young adults with acute and self-resolving cardiomyopathy. In this age group, this entity is frequently interpreted as myocarditis of dilated cardiomyopathy. In younger age group, TCM is cardiomyopathy is triggered by respiratory or gastrointestinal infections, during postsurgical recovery or after neurological insult. Two cases of this syndrome have been reported in fetus after fetal stress. The ECG, biochemical, and echocardiographic parameters of this syndrome in children are similar to that in adults.
| Management|| |
Approach to management
TCM is generally a transient disorder that is managed with supportive therapy. Conservative treatment and resolution of the physical or emotional stress usually result in rapid resolution of symptoms, although some patients develop acute complications such as shock and acute heart failure that require intensive therapy. Appropriate management of shock varies depending on whether significant left ventricular outflow tract (LVOT) obstruction is present. Heart failure management during acute presentation and following stabilization is generally performed according to the standard guidelines except that particular care is taken to avoid volume depletion and vasodilator therapy in patients with LVOT obstruction. Recommendations for anticoagulation to prevent thromboembolism in patients with TCM with LV thrombus or severe LV systolic dysfunction are similar to those for patients post-MI.
Hypotension and shock
Hypotension occurs frequently and it is important to identify the cause of hypotension to determine appropriate management. Approximately 10% of patients with TCM develop cardiogenic shock. Acute pump failure may require intravenous pressor support, but given the evidence of catecholamine excess in the origin of this syndrome, mechanical support with an intra-aortic balloon pump is preferable. There are reports saying that inotropes may be detrimental in this condition. In addition, hypotension may be due to dynamic outflow tract obstruction caused by hyperkinesis of the basal LV segments and systolic anterior motion of the mitral valve.,,, to reduce outflow obstruction, short-acting β-blockers, and intravenous fluids could be used cautiously to decrease contractility and increase cavity size, respectively. Peripheral vasoconstrictors such as phenylephrine may be considered if β-blockers and fluid administration are contraindicated or ineffective.
In-hospital death occurs rarely;, if it occurs, it may be due to the underlying stressor rather than to the cardiomyopathy itself., There are some described incidences of sudden death caused by TCM before evaluation in a hospital or emergency department, but the percentage of such incidence is unknown. The recovery time for LV systolic function varies from several days to several weeks. Empirical approach has been used to treat individuals with TCM as those with other causes of cardiomyopathy (with angiotensin-converting enzyme inhibitors and β-blockers), at least until LV systolic function recovers. Appearance of LV thrombus,, and systemic thromboembolism have been reported. Anticoagulation therapy, at least until recovery of the wall motion abnormality, should be considered for those with clinically significant apical hypokinesis or akinesis that persists 2–3 days after presentation. Recurrence occurs in approximately 10% of patients., Long-term β-blockade and combined α- and β-blockade are attractive therapies given the putative association between TCM and a catecholamine surge. Such strategies have been advocated if patients have no contraindications, but few trial data show efficacy of these strategies.,
| Prognosis and Recurrence|| |
Patients with TCM usually have a good prognosis, and almost perfect recovery is observed in 96% of the cases. Recovery may also take months as demonstrated by speckle-tracking studies. Mortality rate in hospital varies at 0%–8%. TCM was formerly thought to follow a relatively benign course. However, while their long-term survival rate is the same as that in healthy individuals, patients with TCM have a greater risk of death at the time of initial onset. Patients with severe spectrum of TCM may show evidence of LV dysfunction beyond the acute event, in spite of normalization of LV ejection fraction. Recent study shows that there is also formation of myocardial fibrosis detected as early as 4 months inspire of reduction in marrow edema.
| Conclusion|| |
TCM is a recent disease entity characterized by transient LV dysfunction with rapid recovery generally induced by a stressful emotional or physical event. Because of close resemblance of its presentation and clinical course to acute MI, TCM is considered in one of the differential diagnosis for acute MI. Although the cause of this disease has not been completely understood to date, some promising hypotheses have been suggested. The occurrence of this disease is attributed to the large-scale production of catecholamines that causes myocardial hypokinesia through direct cardiomyocyte toxicity and induction of coronary microvascular dysfunction. Recently, unique phenotypes of TCM have been described focusing on its occurrence in younger age group than earlier described. The treatment of TCM still remains controversial.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sato H, Taiteishi H, Uchida T. Takotsubo-type cardiomyopathy due to multivessel spasm. In: Kodama K, Haze K, Hon M, editors. Clinical Aspect of Myocardial Injury: From Ischemia to Heart Failure. Tokyo: Kagakuhyouronsha; 1990. p. 56.
Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: A review of 5 cases. J Cardiol 1991;21:203-14.
Bybee KA, Kara T, Prasad A, Lerman A, Barsness GW, Wright RS, et al.
Systematic review: Transient left ventricular apical ballooning: A syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;141:858-65.
Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, 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;38:11-8.
Abe Y, Kondo M, Matsuoka R, Araki M, Dohyama K, Tanio H. Assessment of clinical features in transient left ventricular apical ballooning. J Am Coll Cardiol 2003;41:737-42.
Hachamovitch R, Chang JD, Kuntz RE, Papageorgiou P, Levin MS, Goldberger AL. Recurrent reversible cardiogenic shock triggered by emotional distress with no obstructive coronary disease. Am Heart J 1995;129:1026-8.
Sharkey SW, Lesser JR, Zenovich AG, Maron MS, Lindberg J, Longe TF, et al.
Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 2005;111:472-9.
Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al.
Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539-48.
Desmet WJ, Adriaenssens BF, Dens JA. Apical ballooning of the left ventricle:First series in white patients. Heart 2003;89:1027-31.
Bybee KA, Prasad A, Barsness GW, Lerman A, Jaffe AS, Murphy JG, et al.
Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am J Cardiol 2004;94:343-6.
Dec GW. Recognition of the apical ballooning syndrome in the United States. Circulation 2005;111:388-90.
Aurigemma GP, Tighe DA. Echocardiography and reversible left ventricular dysfunction. Am J Med 2006;119:18-21.
Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation 2008;118:397-409.
Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): A mimic of acute myocardial infarction. Am Heart J 2008;155:408-17.
Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: A new form of acute, reversible heart failure. Circulation 2008;118:2754-62.
Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al.
Clinical features and outcomes of takotsubo (Stress) cardiomyopathy. N Engl J Med 2015;373:929-38.
Kurowski V, Kaiser A, von Hof K, Killermann DP, Mayer B, Hartmann F, et al.
Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): Frequency, mechanisms, and prognosis. Chest 2007;132:809-16.
Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome or takotsubo cardiomyopathy: A systematic review. Eur Heart J 2006;27:1523-9.
Prasad A, Dangas G, Srinivasan M, Yu J, Gersh BJ, Mehran R, et al.
Incidence and angiographic characteristics of patients with apical ballooning syndrome (takotsubo/stress cardiomyopathy) in the HORIZONS-AMI trial: An analysis from a multicenter, international study of ST-elevation myocardial infarction. Catheter Cardiovasc Interv 2014;83:343-8.
Park JH, Kang SJ, Song JK, Kim HK, Lim CM, Kang DH, et al.
Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest 2005;128:296-302.
Medeiros K, O'Connor MJ, Baicu CF, Fitzgibbons TP, Shaw P, Tighe DA, et al.
Systolic and diastolic mechanics in stress cardiomyopathy. Circulation 2014;129:1659-67.
Park SM, Prasad A, Rihal C, Bell MR, Oh JK. Left ventricular systolic and diastolic function in patients with apical ballooning syndrome compared with patients with acute anterior ST-segment elevation myocardial infarction: A functional paradox. Mayo Clin Proc 2009;84:514-21.
Paur H, Wright PT, Sikkel MB, Tranter MH, Mansfield C, O'Gara P, et al.
High levels of circulating epinephrine trigger apical cardiodepression in a ß2-adrenergic receptor/Gi-dependent manner: A new model of Takotsubo cardiomyopathy. Circulation 2012;126:697-706.
Watanabe H, Kodama M, Okura Y, Aizawa Y, Tanabe N, Chinushi M, et al.
Impact of earthquakes on Takotsubo cardiomyopathy. JAMA 2005;294:305-7.
Nef HM, Möllmann H, Kostin S, Troidl C, Voss S, Weber M, et al.
Tako-Tsubo cardiomyopathy: Intraindividual structural analysis in the acute phase and after functional recovery. Eur Heart J 2007;28:2456-64.
Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, et al.
Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol 2010;55:333-41.
Ito K, Sugihara H, Katoh S, Azuma A, Nakagawa M. Assessment of Takotsubo (ampulla) cardiomyopathy using 99mTc-tetrofosmin myocardial SPECT – Comparison with acute coronary syndrome. Ann Nucl Med 2003;17:115-22.
Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Musha H, Sasaka K. 123I-MIBG myocardial scintigraphy in patients with “takotsubo” cardiomyopathy. J Nucl Med 2004;45:1121-7.
Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nakamura S, et al.
Time course of electrocardiographic changes in patients with tako-tsubo syndrome: Comparison with acute myocardial infarction with minimal enzymatic release. Circ J 2004;68:77-81.
Ueyama T. Emotional stress-induced Tako-tsubo cardiomyopathy: Animal model and molecular mechanism. Ann N
Y Acad Sci 2004;1018:437-44.
Madhavan M, Borlaug BA, Lerman A, Rihal CS, Prasad A. 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;95:1436-41.
Steen H, Merten C, Katus HA, Giannitsis E. Images in cardiovascular medicine. A rare form of midventricular Tako-Tsubo after emotional stress followed up with magnetic resonance imaging. Circulation 2006;114:e248.
Ako J, Sudhir K, Farouque HM, Honda Y, Fitzgerald PJ. Transient left ventricular dysfunction under severe stress: Brain-heart relationship revisited. Am J Med 2006;119:10-7.
Karch SB, Billingham ME. Myocardial contraction bands revisited. Hum Pathol 1986;17:9-13.
Fineschi V, Silver MD, Karch SB, Parolini M, Turillazzi E, Pomara C, et al.
Myocardial disarray: An architectural disorganization linked with adrenergic stress? Int J Cardiol 2005;99:277-82.
Kurisu S, Sato H, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, et al.
Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: A novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 2002;143:448-55.
Heubach JF, Ravens U, Kaumann AJ. Epinephrine activates both Gs and Gi pathways, but norepinephrine activates only the Gs pathway through human beta2-adrenoceptors overexpressed in mouse heart. Mol Pharmacol 2004;65:1313-22.
Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy – A novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5:22-9.
Ibanez B, Navarro F, Cordoba M, M-Alberca P, Farre J. Tako-tsubo transient left ventricular apical ballooning: Is intravascular ultrasound the key to resolve the enigma? Heart 2005;91:102-4.
Haghi D, Roehm S, Hamm K, Harder N, Suselbeck T, Borggrefe M, et al.
Takotsubo cardiomyopathy is not due to plaque rupture: An intravascular ultrasound study. Clin Cardiol 2010;33:307-10.
Delgado GA, Truesdell AG, Kirchner RM, Zuzek RW, Pomerantsev EV, Gordon PC, et al.
An angiographic and intravascular ultrasound study of the left anterior descending coronary artery in takotsubo cardiomyopathy. Am J Cardiol 2011;108:888-91.
Hoyt J, Lerman A, Lennon RJ, Rihal CS, Prasad A. Left anterior descending artery length and coronary atherosclerosis in apical ballooning syndrome (Takotsubo/stress induced cardiomyopathy). Int J Cardiol 2010;145:112-5.
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;144:444-5.
Ikutomi M, Yamasaki M, Matsusita M, Watari Y, Arashi H, Endo G, et al.
Takotsubo cardiomyopathy in siblings. Heart Vessels 2014;29:119-22.
Handy AD, Prasad A, Olson TM. Investigating genetic variation of adrenergic receptors in familial stress cardiomyopathy (apical ballooning syndrome). J Cardiol 2009;54:516-7.
Sharkey SW, Maron BJ, Nelson P, Parpart M, Maron MS, Bristow MR. Adrenergic receptor polymorphisms in patients with stress (tako-tsubo) cardiomyopathy. J Cardiol 2009;53:53-7.
Novo G, Giambanco S, Guglielmo M, Arvigo L, Sutera MR, Giambanco F, et al.
G-protein-coupled receptor kinase 5 polymorphism and Takotsubo cardiomyopathy. J Cardiovasc Med (Hagerstown) 2015;16:639-43.
Goodloe AH, Evans JM, Middha S, Prasad A, Olson TM. Characterizing genetic variation of adrenergic signalling pathways in Takotsubo (stress) cardiomyopathy exomes. Eur J Heart Fail 2014;16:942-9.
Kyuma M, Tsuchihashi K, Shinshi Y, Hase M, Nakata T, Ooiwa H, et al.
Effect of intravenous propranolol on left ventricular apical ballooning without coronary artery stenosis (ampulla cardiomyopathy): Three cases. Circ J 2002;66:1181-4.
Pelliccia F, Parodi G, Greco C, Antoniucci D, Brenner R, Bossone E, et al.
Comorbidities frequency in Takotsubo syndrome: An international collaborative systematic review including 1109 patients. Am J Med 2015;128:654.e11-9.
Krishnamoorthy P, Garg J, Sharma A, Palaniswamy C, Shah N, Lanier G, et al.
Gender differences and predictors of mortality in takotsubo cardiomyopathy: Analysis from the National Inpatient Sample 2009-2010 Database. Cardiology 2015;132:131-6.
Villareal RP, Achari A, Wilansky S, Wilson JM. Anteroapical stunning and left ventricular outflow tract obstruction. Mayo Clin Proc 2001;76:79-83.
Barrera-Ramirez CF, Jimenez-Mazuecos JM, Alfonso F. Apical thrombus associated with left ventricular apical ballooning. Heart 2003;89:927.
Rautaharju PM, Zhang ZM, Haisty WK Jr., Gregg RE, Warren J, Horacek MB, et al.
Race- and sex-associated differences in rate-adjusted QT, QTpeak, ST elevation and other regional measures of repolarization: The Atherosclerosis Risk in Communities (ARIC) Study. J Electrocardiol 2014;47:342-50.
Ogura R, Hiasa Y, Takahashi T, Yamaguchi K, Fujiwara K, Ohara Y, 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;67:687-90.
Neil CJ, Nguyen TH, Singh K, Raman B, Stansborough J, Dawson D, et al.
Relation of delayed recovery of myocardial function after takotsubo cardiomyopathy to subsequent quality of life. Am J Cardiol 2015;115:1085-9.
Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, Carbone I, Muellerleile K, Aldrovandi A, et al.
Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 2011;306:277-86.
Win CM, Pathak A, Guglin M. Not takotsubo: A different form of stress-induced cardiomyopathy – A case series. Congest Heart Fail 2011;17:38-41.
Haghi D, Athanasiadis A, Papavassiliu T, Suselbeck T, Fluechter S, Mahrholdt H, et al.
Right ventricular involvement in Takotsubo cardiomyopathy. Eur Heart J 2006;27:2433-9.
Elesber AA, Prasad A, Bybee KA, Valeti U, Motiei A, Lerman A, et al.
Transient cardiac apical ballooning syndrome: Prevalence and clinical implications of right ventricular involvement. J Am Coll Cardiol 2006;47:1082-3.
Singh K, Neil CJ, Nguyen TH, Stansborough J, Chong CR, Dawson D, et al.
Dissociation of early shock in takotsubo cardiomyopathy from either right or left ventricular systolic dysfunction. Heart Lung Circ 2014;23:1141-8.
Eitel I, Behrendt F, Schindler K, Kivelitz D, Gutberlet M, Schuler G, et al.
Differential diagnosis of suspected apical ballooning syndrome using contrast-enhanced magnetic resonance imaging. Eur Heart J 2008;29:2651-9.
Testa M, Feola M. Usefulness of myocardial positron emission tomography/nuclear imaging in Takotsubo cardiomyopathy. World J Radiol 2014;6:502-6.
Sengupta S, Alsi V, Mohan V, Kaur B, Mohan JC. Unique phenotypes of typical and inverted Takotsubo cardiomyopathy in young females. Indian Heart J 2010;62:348-50.
Daka MA, Khan RS, Deppert EJ. Transient left ventricular apical ballooning after a cocaine binge. J Invasive Cardiol 2007;19:E378-80.
Rivera JM, Locketz AJ, Fritz KD, Horlocker TT, Lewallen DG, Prasad A, et al.
“Broken heart syndrome” after separation (from OxyContin). Mayo Clin Proc 2006;81:825-8.
Dorfman T, Aqel R, Allred J, Woodham R, Iskandrian AE. Takotsubo cardiomyopathy induced by treadmill exercise testing: An insight into the pathophysiology of transient left ventricular apical (or midventricular) ballooning in the absence of obstructive coronary artery disease. J Am Coll Cardiol 2007;49:1223-5.
Cherian J, Kothari S, Angelis D, Atef A, Downey B, Kirkpatrick J Jr. Atypical takotsubo cardiomyopathy: Dobutamine-precipitated apical ballooning with left ventricular outflow tract obstruction. Tex Heart Inst J 2008;35:73-5.
Dundon BK, Puri R, Leong DP, Worthley MI. Takotsubo cardiomyopathy following lightning strike. Emerg Med J 2008;25:460-1.
Citro R, Pascotto M, Provenza G, Gregorio G, Bossone E. Transient left ventricular ballooning (tako-tsubo cardiomyopathy) soon after intravenous ergonovine injection following caesarean delivery. Int J Cardiol 2010;138:e31-4.
Rossor AM, Pearce SH, Adams PC. Left ventricular apical ballooning (takotsubo cardiomyopathy) in thyrotoxicosis. Thyroid 2007;17:181-2.
Citro R, Pontone G, Pace L, Zito C, Silverio A, Bossone E, et al.
Contemporary imaging in takotsubo syndrome. Heart Fail Clin 2016;12:559-75.
Hernandez LE. Takotsubo cardiomyopathy: How much do we know of this syndrome in children and young adults? Cardiol Young 2014;24:580-92.
Lee HR, Hurst RT, Vargas HE. Transient left ventricular apical ballooning syndrome (Takotsubo cardiomyopathy) following orthotopic liver transplantation. Liver Transpl 2007;13:1343-5.
Thorne KD, Kerut EK, MooreCK. Apical ballooning “Takotsubo” syndrome associated with transient left ventricular outflow tract obstruction. Echocardiography 2007;24:770-2.
Syed IS, Prasad A, Oh JK, Martinez MW, Feng D, Motiei A, et al.
Apical ballooning syndrome or aborted acute myocardial infarction? Insights from cardiovascular magnetic resonance imaging. Int J Cardiovasc Imaging 2008;24:875-82.
Yoshioka T, Hashimoto A, Tsuchihashi K, Nagao K, Kyuma M, Ooiwa H, et al.
Clinical implications of midventricular obstruction and intravenous propranolol use in transient left ventricular apical ballooning (Tako-tsubo cardiomyopathy). Am Heart J 2008;155:526.e1-7.
Raddino R, Pedrinazzi C, Zanini G, Robba D, Portera C, Bonadei I, et al.
Out-of-hospital cardiac arrest caused by transient left ventricular apical ballooning syndrome. Int J Cardiol 2008;128:e31-3.
Sasaki N, Kinugawa T, Yamawaki M, Furuse Y, Shimoyama M, Ogino K, et al.
Transient left ventricular apical ballooning in a patient with bicuspid aortic valve created a left ventricular thrombus leading to acute renal infarction. Circ J 2004;68:1081-3.
Andò G, Saporito F, Trio O, Cerrito M, Oreto G, Arrigo F. Systemic embolism in takotsubo syndrome. Int J Cardiol 2009;134:e42-3.
Elesber AA, Prasad A, Lennon RJ, Wright RS, Lerman A, Rihal CS. Four-year recurrence rate and prognosis of the apical ballooning syndrome. J Am Coll Cardiol 2007;50:448-52.
Nowak R, Fijalkowska M, Gilis-Malinowska N, Jaguszewski M, Galaska R, Rojek A, et al.
Left ventricular function after takotsubo is not fully recovered in long-term follow-up: A speckle tracking echocardiography study. Cardiol J 2017;24:57-64.
Dib C, Prasad A, Friedman PA, Ahmad E, Rihal CS, Hammill SC, et al.
Malignant arrhythmia in apical ballooning syndrome: Risk factors and outcomes. Indian Pacing Electrophysiol J 2008;8:182-92.
Schwarz K, Ahearn T, Srinivasan J, Neil CJ, Scally C, Rudd A, et al.
Alterations in cardiac deformation, timing of contraction and relaxation, and early myocardial fibrosis accompany the apparent recovery of acute stress-induced (Takotsubo) cardiomyopathy: An end to the concept of transience. J Am Soc Echocardiogr 2017. pii: S0894-731730216-X.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]