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Literature Review

Multiple Unfavorable Echocardiographic Findings in Takotsubo Cardiomyopathy Are Associated with Increased In-Hospital Events and Mortality

Kagiyama N, Okura H, Matsue Y, et al. J Am Soc Echocardiogr. 2016;29(12):1179-1187.

Reviewers:Alan Hoang, MD1; Antonio Hernandez Conte, MD MBA2

  1. University of California–Irvine, Orange, CA
  2. Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA

Takotsubo cardiomyopathy, also known as “broken heart syndrome,” is a transient cardiac condition associated with physical or emotional stressors. Evaluation reveals left ventricular (LV) wall motion abnormalities that resemble a “tako tsubo”—a Japanese octopus trap. This condition is usually temporary and generally carries a very favorable prognosis. However, significant complications resulting in adverse outcomes have recently been associated with takotsubo cardiomyopathy, including acute heart failure, cardiogenic shock, ventricular tachyarrhythmia, and cardiac rupture. Additionally, poor prognosis has been associated with individual unfavorable echocardiographic findings, including right ventricular (RV) involvement, mitral regurgitation (MR), left ventricular outflow tract (LVOT) obstruction, LV thrombus, and apical ballooning. The purpose of this study is to explore the association between adverse outcomes and multiple unfavorable echocardiographic findings in individual patients with takotsubo cardiomyopathy.


This study was a retrospective review of all patients diagnosed with takotsubo cardiomyopathy at a single medical center over a period of almost 14 years. Patients were excluded if there were insufficient echocardiographic images or they did not meet the Mayo Clinic’s criteria for takotsubo cardiomyopathy:

Based on the number of unfavorable echocardiographic findings, patients were stratified into three groups: low risk (zero to one findings), intermediate risk (two findings), and high risk (three or more findings). Following this classification, characteristics and outcomes were compared among the groups, especially with regard to in-hospital clinical events, defined as acute heart failure with Killip class ≥3, cardiogenic shock, cardiac rupture, sustained ventricular tachyarrhythmia, and in-hospital death of any cause.

Demographic, medical history, laboratory, and echocardiographic parameter data were compared between the three risk-stratified groups. Categorical variables were compared using a chi-squared test. A univariate logistic regression model was used to evaluate the association between multiple unfavorable echocardiographic findings and in-hospital clinical events. Receiver operating characteristic curve analysis using area under the curve (AUC) and continuous net reclassification improvement (NRI) of the logistic regression models was used to compare known clinical factors associated with adverse outcomes (age, gender, ST-segment elevation, physical trigger, and LV ejection fraction) to known clinical factors combined with risk-stratification group.


A total of 113 patients were included in the study. With regard to unfavorable echocardiographic findings, patients had an average of 1.24 ± 0.89 findings. The most common finding was apical ballooning (81.4%), followed by RV involvement (18.6%), significant MR (15%), LVOT obstruction (9.7%), and LV thrombus (2.7%). Risk-stratification classified 68.1% as low risk, 22.1% as intermediate risk, and 9.7% as high risk.

The incidence of both in-hospital critical events and in-hospital deaths was significantly different among the three groups, with intermediate risk greater than low risk, and high risk greater than intermediate risk. Univariate logistic regression model revealed that the intermediate- and high-risk groups were associated with increased in-hospital events, and the high-risk group was associated with increased in-hospital death.

Receiver operating characteristic curve analysis showed increased AUC with risk-stratification based on unfavorable echocardiographic findings with known clinical factors over solely clinical factors, but this increase was not significant (P>.05). However, NRI did reach significance with the addition of the risk stratification.


Although takotsubo cardiomyopathy generally is considered a transient and benign condition, there have been increasing reports of major complications and even death. Past studies have associated unfavorable echocardiographic findings with these complications and poor prognosis, but this study establishes an association between increased number of unfavorable echocardiographic findings and adverse outcomes.

Of note, researchers concluded that apical ballooning itself can be considered an independent unfavorable echocardiographic finding, based on findings from Mansencal et al. that absence of apical ballooning was associated with superior LV ejection fraction and decreased acute complications. In this study, apical ballooning is present in all high- and intermediate-risk patients and comprises the vast majority of the patients in the low-risk group. As such, without analyzing patients with apical ballooning separately, it is difficult to draw the conclusion from this study that it can be considered an independent finding that is associated with adverse outcome. Since apical ballooning is so prevalent, it might have been useful to further stratify patients. For example, low-risk patients could be divided into three other groups, including no findings, apical ballooning only, and one finding excluding apical ballooning.

As this study was retrospective in nature, echocardiographic images were meticulously examined with five specific unfavorable findings in mind. Consequently, it may be difficult to accurately risk-stratify patients prospectively based on the presence of these findings if the ordering clinician, echocardiographer, or interpreting physician does not suspect takotsubo cardiomyopathy or if the echo study is limited. However, with suspicion that in-hospital mortality is underestimated and recent findings that up to one-fifth of patients may experience major in-hospital complications, identifying at-risk patients to provide appropriate care is increasingly pertinent.2,3

  1. 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(3): 408-17.
  2. Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation. 2008;118(25):2754-62.
  3. Templin C, Ghadri JR, Diekmann J, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med. 2015;373(10):929-38.