274
Letters to the Editor
Diagnostic criteria for takotsubo syndrome: A call for consensus Björn Redfors a,b,⁎, Yangzhen Shao b, Alexander R. Lyon c, Elmir Omerovic a,b a b c
Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Molecular and Clinical Medicine/C, Sahlgrenska Academy, Gothenburg University, Sweden NIHR, Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK
a r t i c l e
i n f o
Article history: Received 6 May 2014 Accepted 29 June 2014 Available online 8 July 2014 Keywords: Takotsubo Stress-induced cardiomyopathy Diagnostic criteria
Letter to the Editor: Takotsubo syndrome (TS), also known as stress-induced cardiomyopathy, is an acute cardiac syndrome associated with significant mortality and morbidity. It is found in approximately 2–5% of patients presenting with acute coronary syndromes (ACS). TS patients typically receive ACS therapy, the consequences of which are largely unknown but may lead to unnecessary complications. It is therefore important to develop diagnostic criteria for TS that can reliably identify these patients. Since the first Mayo criteria were published in 2004, several groups have suggested their own diagnostic criteria, some of which have subsequently been refined (Table 1) [1]. Although these various criteria are important to help clinicians identify patients with TS, there are some discrepancies between these criteria, and regional cohorts of TS patients are still too small to adequately power retrospective analyses on patient characteristics, treatment strategies and/or outcome. International consensus on diagnostic criteria particularly under the auspices of European and American cardiology societies would allow for better extrapolation of data across different studies and populations. In this letter, we briefly discuss the available TS criteria, including our own. The first Mayo criteria were published in 2004 [1–5]. These criteria were important as they increased awareness about the syndrome around the world and described TS in simple terms that could be implemented in clinical practice. Because little was known about TS at the time the criteria were published, the authors insightfully predicted that the criteria would need to be revised in the future as our knowledge increases. Unfortunately, many colleagues still adhere to the original Mayo criteria despite substantial evidence in support of the argument that these criteria are now obsolete. Most importantly, these criteria are considered too strict as they exclude patients with significant coronary artery disease (CAD), pheochromocytoma or intracranial lesions. Compelling evidence now indicates that CAD and TS coexist and TS is particularly common in patients with pheochromocytoma or intracranial lesions. In an attempt to incorporate recent observations in their criteria, the authors have published revisions of the original criteria, the most recent of which were presented in 2008 and are included in Table 1 [2]. In these revised criteria, the presence of CAD or intracranial lesions no longer excludes patients from a TS diagnosis. However, patients are still excluded from receiving a TS diagnosis if pheochromocytoma is present. Because excess catecholamine is believed to play an important role in TS, we suggest that TS should be considered a possible complication of syndromes associated with excess plasma catecholamine, including pheochromocytoma. ⁎ Corresponding author at: Bruna stråket 16, SE 413 45 Gothenburg, Sweden. Tel.: +46 31 343 7543; fax: + 46 31 823 762. E-mail address: [email protected] (B. Redfors).
The Japanese Takotsubo Cardiomyopathy Study Group published their criteria in 2007 [3]. These authors describe TS as an idiopathic syndrome. Patients with pheochromocytoma or intracranial lesions are excluded from the TS cohort. The authors instead regard these patients as suffering from “TS-like” cardiac dysfunction but contend that TS is not idiopathic in these patients and therefore exclude them from a TS diagnosis. However, a pathophysiological missing link still exists between intracranial injury and/or excess catecholamine and development of TS-like cardiac dysfunction. We believe that TS should not be viewed simply as an idiopathic syndrome, but rather a syndrome that we currently know little about but for which a pathophysiological explanation is within reach. In 2011, we published the first version of the Gothenburg criteria for TS diagnosis. In our experience, numerous patients who presented with characteristic TS-like cardiac dysfunction, and in whom no alternative plausible diagnosis could be identified, failed to adhere to the Mayo criteria and thus could not be diagnosed with TS. Therefore, we proposed a new set of diagnostic criteria in accordance with our clinical observations. Because severe somatic as well as emotional stress is thought to cause TS, most somatic conditions associated with significant stress could be potential triggers of TS. We propose that TS should not be excluded solely on the basis of the presence of another somatic condition. In fact, acute myocardial damage due to myocarditis or ischemia has been implicated as a possible trigger for TS. Based on our experimental and clinical observations that the majority of TS patients have decreased peripheral vascular resistance, near-normal cardiac output and only minimally elevated left ventricular filling pressure, in 2013 we revised the Gothenburg criteria by adding normal or near-normal left ventricular filling pressure [4]. Although some TS patients appear to present with increased filling pressure, left ventricular filling pressures appear to be remarkably low in a large subset of TS patients [6,7]. We propose that TS should be regarded as a cardio-circulatory syndrome with distinct hemodynamic characteristics that differentiate it from ACS. It is quite puzzling that the typical TS patient remains hemodynamically stable despite loss of contractile function in N60% of the left ventricle given the fact that an acute myocardial infarction of similar magnitude would be incompatible with life. We consider this as the most remarkable and counter-intuitive phenomenon of TS. Among the currently available criteria, only the Gothenburg criteria recognize this aspect of TS. We also call for intensified work on development of reliable post mortem pathohistological criteria for patients who regretfully do not survive the acute phase of TS. The Johns Hopkins criteria were published in 2012 and include both mandatory and optional criteria [5]. Although these criteria may appear to differ little from the Gothenburg criteria, they consider evidence of intracoronary plaque rupture to preclude TS. Also, these criteria do not recognize TS unless cardiac dysfunction extends beyond a single coronary artery distribution area. In this aspect, the Johns Hopkins criteria differ from both the revised Mayo criteria and the Gothenburg criteria. The Takotsubo Italian Network (TIN) is an excellent initiative that has contributed to the field with new important insights about TS. Recently these authors proposed their own criteria in which they capture many important characteristics of the syndrome [8]. The novelty is the attempt to quantify two important conditions of TS, namely time to recovery of cardiac function and degree of myocardial injury marker release. However, although clear limits for these criteria would simplify the diagnostic algorithm in TS, the limits appear to be arbitrarily set. Although it is correct to state that cardiac injury markers are only mildly increased in TS patients compared with patients with acute myocardial infarction,
Letters to the Editor Table 1 Different diagnostic criteria that have been proposed for takotsubo.
Table 1 (continued) 2004, Mayo criteria
2004, Mayo criteria
•
Transient akinesis or dyskinesis of the left apical and mid-ventricular segments with regional wall-motion abnormalities extending beyond a single epicardial vascular distribution
•
Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture
•
New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion)
•
Absence of – Recent significant head trauma
275
During the acute stage, abnormal Q-waves and changes in the QRS voltage might be observed. F. Cardiac biomarkers: In a typical case, there are only modest elevations of serum levels of cardiac enzymes and troponin. G. Myocardial radionuclear study: Abnormal findings in myocardial scintigraphy are observed in some cases. H. Prognosis: The majority of the cases rapidly recover, but some cases suffer pulmonary edema and other sequelae or death. 2008, revised Mayo criteria
– Intracranial bleeding
•
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
•
Absence of obstructive coronary disease or angiographic evidence of acute plaque**
•
New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin
•
Absence of: Pheochromocytoma, myocarditis *Rare exceptions to these criteria are recognized, such as those patients in whom the regional wall motion abnormality is limited to a single coronary territory. **The authors recognize that patients with obstructive coronary atherosclerosis may also develop takotsubo cardiomyopathy but consider these patients to be rare.
– Pheochromocytoma – Obstructive epicardial coronary artery disease – Myocarditis – Hypertrophic cardiomyopathy All four criteria must be met 2007, the Japanese Takotsubo Cardiomyopathy Study Group proposal I. Definition: Takotsubo (ampulla) cardiomyopathy is a disease exhibiting an acute left ventricular apical ballooning of unknown cause. In this disease, the left ventricle takes on the shape of a “takotsubo” (Japanese octopus trap). There is nearly complete resolution of the apical akinesis in the majority of the patients within a month. The contraction abnormality occurs mainly in the left ventricle, but involvement of the right ventricle is observed in some cases. A dynamic obstruction of the left ventricular outflow tract (pressure gradient difference, acceleration of blood flow, or systolic cardiac murmurs) is also observed. Note: There are patients, such as cerebrovascular patients, who have an apical systolic ballooning similar to that in takotsubo cardiomyopathy, but with a known cause. Such patients are diagnosed as “cerebrovascular disease with takotsubo-like myocardial dysfunction” and are differentiated from idiopathic cases. II. Exclusion criteria: The following lesions and abnormalities from other diseases must be excluded in the diagnosis of takotsubo (ampulla) cardiomyopathy. A. Significant organic stenosis or spasm of a coronary artery. In particular, acute myocardial infarction due to a lesion of the anterior descending branch of the left coronary artery, which perfuses an extensive territory including the left ventricular apex (an urgent coronary angiogram is desirable for imaging during the acute stage, but coronary angiography is also necessary during the chronic stage to confirm the presence or absence of a significant stenotic lesion or a lesion involved in the abnormal pattern of ventricular contraction). B. Cerebrovascular disease C. Pheochromocytoma D. Viral or idiopathic myocarditis Note: For the exclusion of coronary artery lesions, coronary angiography is required. Takotsubo-like myocardial dysfunction could occur with diseases such as cerebrovascular disease and pheochromocytoma. III. References for diagnosis: A. Symptoms: Chest pain and dyspnea similar to those in acute coronary syndrome. Takotsubo cardiomyopathy can occur without symptoms. B. Triggers: Emotional or physical stress may trigger takotsubo cardiomyopathy, but it can also occur without any apparent trigger. C. Age and gender difference: Known tendency to increase in the elderly, particularly females. D. Ventricular morphology: Apical ballooning and its rapid improvement in the ventriculogram and echocardiogram. E. Electrocardiogram: ST segment elevations might be observed immediately after the onset. Thereafter, in a typical case, the T-wave becomes progressively more negative in multiple leads, and the QT interval prolongs. These changes improve gradually, but a negative T-wave may continue for several months.
2011, Gothenburg criteria
•
Transient hypokinesis, akinesis, or dyskinesis in the left ventricular segments and frequently, but not always, a stressful trigger (psychical or physical)
•
The absence of other pathological conditions (e.g. ischemia, myocarditis, toxic damage, and tachycardia) that may more credibly explain the regional dysfunction
•
No elevation or modest elevation in cardiac troponin (i.e. disparity between the troponin level and the amount of dysfunctional myocardium)
2012, Johns Hopkins criteria Helpful, but not mandatory, criteria
• •
•
An acute identifiable trigger (either emotional or physical) Characteristic ECG changes that may include some or all of the following: – ST-segment elevation at time of admission (often ≤2 mm in magnitude, and usually not associated with reciprocal ST-segment depression)
–
Diffuse deep T-wave inversion (may be present on admission or may evolve during the first several hospital days)
–
QT interval prolongation (usually maximal by 24–48 h)
Mildly elevated cardiac troponin (often appears disproportionately low given the degree of wall motion abnormality)
Mandatory criteria
•
Absence of coronary thrombosis or angiographic evidence of acute plaque rupture
•
Regional ventricular wall motion abnormalities that extend beyond a single epicardial vascular distribution
•
Complete recovery of reginal wall motion abnormalities (usually within days to weeks)
2013, revised Gothenburg criteria
•
Transient hypokinesis, akinesis, or dyskinesis in the left ventricular segments and frequently, but not always, a stressful trigger (psychical or physical)
•
The absence of other pathological conditions (e.g. ischemia, myocarditis, toxic damage, and tachycardia) that more credibly explain the regional dysfunction
•
No elevation or modest elevation in cardiac troponin (i.e. disparity between the troponin level and the amount of dysfunctional myocardium) (continued on next page)
(continued on next page)
276
Letters to the Editor
Table 1 (continued) 2004, Mayo criteria
•
Normal, or near normal left ventricular filling pressure
2014, Takotsubo Italian Network proposal
•
Typical transient LV wall motion abnormalities extending beyond a single epicardial vascular distribution with complete functional normalization within 6 weeks
•
Absence of potentially culprit coronary stenosis, or angiographic evidence of acute plaque rupture, dissection, thrombosis or spasm*
•
New and dynamic ST-segment abnormalities or T-wave inversion as well as new onset of transient or permanent left bundle branch block
•
Mild increase in myocardial injury markers (creatine kinase-MB value b 50 U/L)
• • •
Clinical and/or instrumental exclusion of myocarditis
the levels of myocardial injury markers are related to the amount of affected myocardium. If a large part of the left ventricle is affected, myocardial injury markers may rise to levels well above the limit proposed by the authors. It is probably more accurate to relate the increase in serum myocardial injury markers to the extent of left ventricular involvement rather than stipulate a maximum absolute value. They also introduce two optional criteria, reflecting the epidemiology, namely postmenopausal women and stressful precipitant. These are useful additions, and are most relevant in ‘gray’ or ‘borderline’ cases, and may help guide the clinician towards a diagnosis of TS. In conclusion, each set of proposed criteria contributes significantly to increase awareness about this important syndrome and provides objective support for everyday clinical decision-making. Although differences between the criteria may appear to be small, they are clinically important. International consensus on diagnostic criteria for TS is urgently needed as it would increase patient safety and allow for better extrapolation of data across different studies and populations.
Post-menopausal women (optional)** Antecedent stressful event (optional)** *Coronary angiography should be performed as soon as possible (ideally within 48 h from admission) **Optional diagnostic criteria are not mandatory, but when positive they increase the likelihood of takotsubo syndrome diagnosis
2014, proposed new Gothenburg criteria
•
Transient hypokinesis, akinesis, or dyskinesis in the left ventricular segments and frequently, but not always, a stressful trigger (psychical or physical)
•
The absence of other pathological conditions (e.g. ischemia, myocarditis, toxic damage, tachycardia, etc.) that more credibly explain the regional dysfunction
•
No elevation or modest elevation in cardiac troponin (i.e. disparity between the troponin level and the amount of dysfunctional myocardium)
• •
Normal, or near normal left ventricular filling pressure* Low, or near normal peripheral vascular resistance and normal or near-normal cardiac output* *Optional diagnostic criteria that are not mandatory, but when positive they increase the likelihood of takotsubo syndrome diagnosis
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2014.06.094
References [1] Bybee KA, Kara T, Prasad A, 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. [2] 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. [3] Kawai S, Kitabatake A, Tomoike H, Takotsubo Cardiomyopathy G. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Circ J 2007;71:990–2. [4] Redfors B, Shao Y, Omerovic E. Stress-induced cardiomyopathy (Takotsubo)—broken heart and mind? Vasc Health Risk Manag 2013;9:149–54. [5] Wittstein IS. Stress cardiomyopathy: a syndrome of catecholamine-mediated myocardial stunning? Cell Mol Neurobiol 2012;32:847–57. [6] Chong CR, Neil CJ, Nguyen TH, et al. Dissociation between severity of takotsubo cardiomyopathy and presentation with shock or hypotension. Clin Cardiol 2013;36:401–6. [7] Medeiros K, O'Connor MJ, Baicu CF, et al. Systolic and diastolic mechanics in stress cardiomyopathy. Circulation 2014;129:1659–67. [8] Parodi G, Citro R, Bellandi B, et al. Revised clinical diagnostic criteria for Tako-tsubo syndrome: the Tako-tsubo Italian Network proposal. Int J Cardiol 2014 Mar 1;172:282–3.
Letters to the Editor
Diagnostic criteria for takotsubo syndrome: A call for consensus Björn Redfors a,b,⁎, Yangzhen Shao b, Alexander R. Lyon c, Elmir Omerovic a,b a b c
Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Molecular and Clinical Medicine/C, Sahlgrenska Academy, Gothenburg University, Sweden NIHR, Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK
a r t i c l e
i n f o
Article history: Received 6 May 2014 Accepted 29 June 2014 Available online 8 July 2014 Keywords: Takotsubo Stress-induced cardiomyopathy Diagnostic criteria
Letter to the Editor: Takotsubo syndrome (TS), also known as stress-induced cardiomyopathy, is an acute cardiac syndrome associated with significant mortality and morbidity. It is found in approximately 2–5% of patients presenting with acute coronary syndromes (ACS). TS patients typically receive ACS therapy, the consequences of which are largely unknown but may lead to unnecessary complications. It is therefore important to develop diagnostic criteria for TS that can reliably identify these patients. Since the first Mayo criteria were published in 2004, several groups have suggested their own diagnostic criteria, some of which have subsequently been refined (Table 1) [1]. Although these various criteria are important to help clinicians identify patients with TS, there are some discrepancies between these criteria, and regional cohorts of TS patients are still too small to adequately power retrospective analyses on patient characteristics, treatment strategies and/or outcome. International consensus on diagnostic criteria particularly under the auspices of European and American cardiology societies would allow for better extrapolation of data across different studies and populations. In this letter, we briefly discuss the available TS criteria, including our own. The first Mayo criteria were published in 2004 [1–5]. These criteria were important as they increased awareness about the syndrome around the world and described TS in simple terms that could be implemented in clinical practice. Because little was known about TS at the time the criteria were published, the authors insightfully predicted that the criteria would need to be revised in the future as our knowledge increases. Unfortunately, many colleagues still adhere to the original Mayo criteria despite substantial evidence in support of the argument that these criteria are now obsolete. Most importantly, these criteria are considered too strict as they exclude patients with significant coronary artery disease (CAD), pheochromocytoma or intracranial lesions. Compelling evidence now indicates that CAD and TS coexist and TS is particularly common in patients with pheochromocytoma or intracranial lesions. In an attempt to incorporate recent observations in their criteria, the authors have published revisions of the original criteria, the most recent of which were presented in 2008 and are included in Table 1 [2]. In these revised criteria, the presence of CAD or intracranial lesions no longer excludes patients from a TS diagnosis. However, patients are still excluded from receiving a TS diagnosis if pheochromocytoma is present. Because excess catecholamine is believed to play an important role in TS, we suggest that TS should be considered a possible complication of syndromes associated with excess plasma catecholamine, including pheochromocytoma. ⁎ Corresponding author at: Bruna stråket 16, SE 413 45 Gothenburg, Sweden. Tel.: +46 31 343 7543; fax: + 46 31 823 762. E-mail address: [email protected] (B. Redfors).
The Japanese Takotsubo Cardiomyopathy Study Group published their criteria in 2007 [3]. These authors describe TS as an idiopathic syndrome. Patients with pheochromocytoma or intracranial lesions are excluded from the TS cohort. The authors instead regard these patients as suffering from “TS-like” cardiac dysfunction but contend that TS is not idiopathic in these patients and therefore exclude them from a TS diagnosis. However, a pathophysiological missing link still exists between intracranial injury and/or excess catecholamine and development of TS-like cardiac dysfunction. We believe that TS should not be viewed simply as an idiopathic syndrome, but rather a syndrome that we currently know little about but for which a pathophysiological explanation is within reach. In 2011, we published the first version of the Gothenburg criteria for TS diagnosis. In our experience, numerous patients who presented with characteristic TS-like cardiac dysfunction, and in whom no alternative plausible diagnosis could be identified, failed to adhere to the Mayo criteria and thus could not be diagnosed with TS. Therefore, we proposed a new set of diagnostic criteria in accordance with our clinical observations. Because severe somatic as well as emotional stress is thought to cause TS, most somatic conditions associated with significant stress could be potential triggers of TS. We propose that TS should not be excluded solely on the basis of the presence of another somatic condition. In fact, acute myocardial damage due to myocarditis or ischemia has been implicated as a possible trigger for TS. Based on our experimental and clinical observations that the majority of TS patients have decreased peripheral vascular resistance, near-normal cardiac output and only minimally elevated left ventricular filling pressure, in 2013 we revised the Gothenburg criteria by adding normal or near-normal left ventricular filling pressure [4]. Although some TS patients appear to present with increased filling pressure, left ventricular filling pressures appear to be remarkably low in a large subset of TS patients [6,7]. We propose that TS should be regarded as a cardio-circulatory syndrome with distinct hemodynamic characteristics that differentiate it from ACS. It is quite puzzling that the typical TS patient remains hemodynamically stable despite loss of contractile function in N60% of the left ventricle given the fact that an acute myocardial infarction of similar magnitude would be incompatible with life. We consider this as the most remarkable and counter-intuitive phenomenon of TS. Among the currently available criteria, only the Gothenburg criteria recognize this aspect of TS. We also call for intensified work on development of reliable post mortem pathohistological criteria for patients who regretfully do not survive the acute phase of TS. The Johns Hopkins criteria were published in 2012 and include both mandatory and optional criteria [5]. Although these criteria may appear to differ little from the Gothenburg criteria, they consider evidence of intracoronary plaque rupture to preclude TS. Also, these criteria do not recognize TS unless cardiac dysfunction extends beyond a single coronary artery distribution area. In this aspect, the Johns Hopkins criteria differ from both the revised Mayo criteria and the Gothenburg criteria. The Takotsubo Italian Network (TIN) is an excellent initiative that has contributed to the field with new important insights about TS. Recently these authors proposed their own criteria in which they capture many important characteristics of the syndrome [8]. The novelty is the attempt to quantify two important conditions of TS, namely time to recovery of cardiac function and degree of myocardial injury marker release. However, although clear limits for these criteria would simplify the diagnostic algorithm in TS, the limits appear to be arbitrarily set. Although it is correct to state that cardiac injury markers are only mildly increased in TS patients compared with patients with acute myocardial infarction,
Letters to the Editor Table 1 Different diagnostic criteria that have been proposed for takotsubo.
Table 1 (continued) 2004, Mayo criteria
2004, Mayo criteria
•
Transient akinesis or dyskinesis of the left apical and mid-ventricular segments with regional wall-motion abnormalities extending beyond a single epicardial vascular distribution
•
Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture
•
New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion)
•
Absence of – Recent significant head trauma
275
During the acute stage, abnormal Q-waves and changes in the QRS voltage might be observed. F. Cardiac biomarkers: In a typical case, there are only modest elevations of serum levels of cardiac enzymes and troponin. G. Myocardial radionuclear study: Abnormal findings in myocardial scintigraphy are observed in some cases. H. Prognosis: The majority of the cases rapidly recover, but some cases suffer pulmonary edema and other sequelae or death. 2008, revised Mayo criteria
– Intracranial bleeding
•
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
•
Absence of obstructive coronary disease or angiographic evidence of acute plaque**
•
New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin
•
Absence of: Pheochromocytoma, myocarditis *Rare exceptions to these criteria are recognized, such as those patients in whom the regional wall motion abnormality is limited to a single coronary territory. **The authors recognize that patients with obstructive coronary atherosclerosis may also develop takotsubo cardiomyopathy but consider these patients to be rare.
– Pheochromocytoma – Obstructive epicardial coronary artery disease – Myocarditis – Hypertrophic cardiomyopathy All four criteria must be met 2007, the Japanese Takotsubo Cardiomyopathy Study Group proposal I. Definition: Takotsubo (ampulla) cardiomyopathy is a disease exhibiting an acute left ventricular apical ballooning of unknown cause. In this disease, the left ventricle takes on the shape of a “takotsubo” (Japanese octopus trap). There is nearly complete resolution of the apical akinesis in the majority of the patients within a month. The contraction abnormality occurs mainly in the left ventricle, but involvement of the right ventricle is observed in some cases. A dynamic obstruction of the left ventricular outflow tract (pressure gradient difference, acceleration of blood flow, or systolic cardiac murmurs) is also observed. Note: There are patients, such as cerebrovascular patients, who have an apical systolic ballooning similar to that in takotsubo cardiomyopathy, but with a known cause. Such patients are diagnosed as “cerebrovascular disease with takotsubo-like myocardial dysfunction” and are differentiated from idiopathic cases. II. Exclusion criteria: The following lesions and abnormalities from other diseases must be excluded in the diagnosis of takotsubo (ampulla) cardiomyopathy. A. Significant organic stenosis or spasm of a coronary artery. In particular, acute myocardial infarction due to a lesion of the anterior descending branch of the left coronary artery, which perfuses an extensive territory including the left ventricular apex (an urgent coronary angiogram is desirable for imaging during the acute stage, but coronary angiography is also necessary during the chronic stage to confirm the presence or absence of a significant stenotic lesion or a lesion involved in the abnormal pattern of ventricular contraction). B. Cerebrovascular disease C. Pheochromocytoma D. Viral or idiopathic myocarditis Note: For the exclusion of coronary artery lesions, coronary angiography is required. Takotsubo-like myocardial dysfunction could occur with diseases such as cerebrovascular disease and pheochromocytoma. III. References for diagnosis: A. Symptoms: Chest pain and dyspnea similar to those in acute coronary syndrome. Takotsubo cardiomyopathy can occur without symptoms. B. Triggers: Emotional or physical stress may trigger takotsubo cardiomyopathy, but it can also occur without any apparent trigger. C. Age and gender difference: Known tendency to increase in the elderly, particularly females. D. Ventricular morphology: Apical ballooning and its rapid improvement in the ventriculogram and echocardiogram. E. Electrocardiogram: ST segment elevations might be observed immediately after the onset. Thereafter, in a typical case, the T-wave becomes progressively more negative in multiple leads, and the QT interval prolongs. These changes improve gradually, but a negative T-wave may continue for several months.
2011, Gothenburg criteria
•
Transient hypokinesis, akinesis, or dyskinesis in the left ventricular segments and frequently, but not always, a stressful trigger (psychical or physical)
•
The absence of other pathological conditions (e.g. ischemia, myocarditis, toxic damage, and tachycardia) that may more credibly explain the regional dysfunction
•
No elevation or modest elevation in cardiac troponin (i.e. disparity between the troponin level and the amount of dysfunctional myocardium)
2012, Johns Hopkins criteria Helpful, but not mandatory, criteria
• •
•
An acute identifiable trigger (either emotional or physical) Characteristic ECG changes that may include some or all of the following: – ST-segment elevation at time of admission (often ≤2 mm in magnitude, and usually not associated with reciprocal ST-segment depression)
–
Diffuse deep T-wave inversion (may be present on admission or may evolve during the first several hospital days)
–
QT interval prolongation (usually maximal by 24–48 h)
Mildly elevated cardiac troponin (often appears disproportionately low given the degree of wall motion abnormality)
Mandatory criteria
•
Absence of coronary thrombosis or angiographic evidence of acute plaque rupture
•
Regional ventricular wall motion abnormalities that extend beyond a single epicardial vascular distribution
•
Complete recovery of reginal wall motion abnormalities (usually within days to weeks)
2013, revised Gothenburg criteria
•
Transient hypokinesis, akinesis, or dyskinesis in the left ventricular segments and frequently, but not always, a stressful trigger (psychical or physical)
•
The absence of other pathological conditions (e.g. ischemia, myocarditis, toxic damage, and tachycardia) that more credibly explain the regional dysfunction
•
No elevation or modest elevation in cardiac troponin (i.e. disparity between the troponin level and the amount of dysfunctional myocardium) (continued on next page)
(continued on next page)
276
Letters to the Editor
Table 1 (continued) 2004, Mayo criteria
•
Normal, or near normal left ventricular filling pressure
2014, Takotsubo Italian Network proposal
•
Typical transient LV wall motion abnormalities extending beyond a single epicardial vascular distribution with complete functional normalization within 6 weeks
•
Absence of potentially culprit coronary stenosis, or angiographic evidence of acute plaque rupture, dissection, thrombosis or spasm*
•
New and dynamic ST-segment abnormalities or T-wave inversion as well as new onset of transient or permanent left bundle branch block
•
Mild increase in myocardial injury markers (creatine kinase-MB value b 50 U/L)
• • •
Clinical and/or instrumental exclusion of myocarditis
the levels of myocardial injury markers are related to the amount of affected myocardium. If a large part of the left ventricle is affected, myocardial injury markers may rise to levels well above the limit proposed by the authors. It is probably more accurate to relate the increase in serum myocardial injury markers to the extent of left ventricular involvement rather than stipulate a maximum absolute value. They also introduce two optional criteria, reflecting the epidemiology, namely postmenopausal women and stressful precipitant. These are useful additions, and are most relevant in ‘gray’ or ‘borderline’ cases, and may help guide the clinician towards a diagnosis of TS. In conclusion, each set of proposed criteria contributes significantly to increase awareness about this important syndrome and provides objective support for everyday clinical decision-making. Although differences between the criteria may appear to be small, they are clinically important. International consensus on diagnostic criteria for TS is urgently needed as it would increase patient safety and allow for better extrapolation of data across different studies and populations.
Post-menopausal women (optional)** Antecedent stressful event (optional)** *Coronary angiography should be performed as soon as possible (ideally within 48 h from admission) **Optional diagnostic criteria are not mandatory, but when positive they increase the likelihood of takotsubo syndrome diagnosis
2014, proposed new Gothenburg criteria
•
Transient hypokinesis, akinesis, or dyskinesis in the left ventricular segments and frequently, but not always, a stressful trigger (psychical or physical)
•
The absence of other pathological conditions (e.g. ischemia, myocarditis, toxic damage, tachycardia, etc.) that more credibly explain the regional dysfunction
•
No elevation or modest elevation in cardiac troponin (i.e. disparity between the troponin level and the amount of dysfunctional myocardium)
• •
Normal, or near normal left ventricular filling pressure* Low, or near normal peripheral vascular resistance and normal or near-normal cardiac output* *Optional diagnostic criteria that are not mandatory, but when positive they increase the likelihood of takotsubo syndrome diagnosis
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2014.06.094
References [1] Bybee KA, Kara T, Prasad A, 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. [2] 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. [3] Kawai S, Kitabatake A, Tomoike H, Takotsubo Cardiomyopathy G. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Circ J 2007;71:990–2. [4] Redfors B, Shao Y, Omerovic E. Stress-induced cardiomyopathy (Takotsubo)—broken heart and mind? Vasc Health Risk Manag 2013;9:149–54. [5] Wittstein IS. Stress cardiomyopathy: a syndrome of catecholamine-mediated myocardial stunning? Cell Mol Neurobiol 2012;32:847–57. [6] Chong CR, Neil CJ, Nguyen TH, et al. Dissociation between severity of takotsubo cardiomyopathy and presentation with shock or hypotension. Clin Cardiol 2013;36:401–6. [7] Medeiros K, O'Connor MJ, Baicu CF, et al. Systolic and diastolic mechanics in stress cardiomyopathy. Circulation 2014;129:1659–67. [8] Parodi G, Citro R, Bellandi B, et al. Revised clinical diagnostic criteria for Tako-tsubo syndrome: the Tako-tsubo Italian Network proposal. Int J Cardiol 2014 Mar 1;172:282–3.
