The very interesting and timely study by Sy et al, published on May 16, 2013 online ahead of print in The American Journal of Cardiology , is an example of the underdiagnosis of Takotsubo syndrome (TTS), resulting from adherence to the currently prevailing Mayo Clinic diagnostic TTS criteria. The revised version of these criteria requires that obstructive coronary artery disease, based on coronary arteriography and pheochromocytoma, be ruled out before making the diagnosis of TTS. The investigators set out to evaluate prospectively the frequency of TTS in peri-, and postmenopausal women (age ≥45 years old) in a consecutive series of 1,297 patients with an increase in cardiac troponin I. Of which, 323 (24.9%) satisfied the criteria for acute myocardial infarction according to the universal definition of myocardial infarction and 19 (5.9%) met the criteria for TTS. Three more patients who also had TTS were separately mentioned because they had TTS in conjunction with a neurologic primary diagnosis. However, the investigators presented them separately hesitating implicitly to include them in the group of 19 with TTS, presumably because the original Mayo Clinic diagnostic criteria for TTS excluded such a diagnosis in the presence of neurologic illnesses, and the current revised criteria still include diagnosis of pheochromocytoma as a reason to exclude a diagnosis of TTS. The investigators concluded that TTS may be more common (5.7%) than previously reported (1% to 2.2%) in postmenopausal women presenting with a clinical picture of an acute coronary syndrome (ACS), although their patient study population denominator (SPD) included patients with an acute myocardial infarction, and not ACS. The study has some limitations, which the investigators recognize, particularly the lack of a repeat imaging evaluation proving the improvement or restoration to normal of the initially impaired left ventricular function, which is a sine qua nonelement in the diagnosis of TTS in published works ( http://www.ncbi.nlm.nih.gov/pubmed/?term=takotsubo ). The investigators could not do better considering the current prevailing diagnostic constrains, considering that they had to start by using the diagnostic TTS model employing the “filter” of an SPD with suspected ACS on the basis of clinical presentation of chest pain, dyspnea, electrocardiographic changes, and elevated troponin I levels. Of course this is not what should be the case, and ideally all the patients who presented with chest pain or dyspnea or palpitations, including those who died or were discharged, should be the right denominator from whom the case of TTS should have been drawn. Because this is impractical, one should go to the next best SPD, which is the cohort of patients who presented with chest pain or dyspnea or palpitations, irrespective of the results of the troponin I test. Probably, such a study population will not be more revealing, and the authors anticipated this and commented that such patients would be expected to have a very low frequency of TTS. Because patients with eventually proved TTS may present without troponin I increase, and even with a normal or “near normal” electrocardiogram, one wonders whether the appropriate SPD should be patients with suggestive symptomatology, with an expeditiously performed echocardiography in the emergency department showing cardiac wall motion abnormalities with depressed left ventricular function. Such SPD should be reevaluated before hospital discharge and at the outpatient follow-up with repeat echocardiography, and diagnosis of TTS should be based on the proof that cardiac wall motion abnormalities have been markedly ameliorated or disappeared and that left ventricular function has improved or restored to normal. Thus, this notion forwards the thesis that TTS diagnosis should be based on serial echocardiography and not on the negative results of a coronary arteriogram, which is the current model according to Mayo Clinic TTS diagnostic criteria. Indeed, we should start entertaining the notion that TTS can overlap with obstructive coronary artery disease or even ACS because the authors commented that “any illness has the potential to trigger TTS and the diagnosis should be considered in all hospitalized patients with medical or surgical conditions who develop unexplained heart failure or left ventricular (LV) dysfunction.”