We appreciate the comments and insights from Dr. Manfredini and colleagues and Dr. Deshmukh concerning the determinants and circadian patterns associated with tako-tsubo cardiomyopathy events. Although this condition has been described for >20 years and has attracted the interest and energies of many investigators throughout the world, its pathophysiology and mechanisms at present remain largely undefined. This is substantiated by the observations of Manfredini et al, who have surveyed published takotsubo research with respect to circadian variability for the time of day, day of the week, and month (season). Certainly, for a condition as heterogenous as takotsubo cardiomyopathy, the differences reported for onset time are perhaps not unexpected, given the potential influence of emotional and physical stressors and the geographic, cultural, and community diversity of the affected patients.

In our data, we have found takotsubo events (predominantly in women) more common in the afternoon hours, but ST-segment myocardial infarction most frequent in the morning (consistent with published data on atherosclerotic coronary artery disease), different from the afternoon predilection of tako-tsubo. The 2,975 patients studied with ST-segment elevation myocardial infarction included 803 women in whom onset time was also most frequent in the morning. The 2 populations in our study were, in fact, culturally and geographically similar.

The preferential occurrence of takotsubo cardiomyopathy in the afternoon hours seems to us consistent with the time at which the typical triggering events for this condition typically occur. However, it is not at all surprising to us that the timing of takotsubo events would differ among diverse patient populations, as suggested here by Manfredini et al and Deshmukh, as well as by our group.

There is increasing awareness that a subset of women experience acute myocardial infarctions in the absence of significant obstructive coronary artery disease. It has been proposed that this phenomenon is due to an atherosclerotic event caused by angiographically unapparent plaque erosion or rupture with subsequent transient thrombosis, embolism, or vasospasm and may even include women with takotsubo cardiomyopathy. Although the basic determinants of takotsubo cardiomyopathy remain elusive, we believe the circadian patterns identified in our study represent another piece of evidence supporting mechanisms other than acute coronary plaque disruption with spontaneous lysis of thrombus, vasospasm, or embolism in the pathophysiology of this novel tako-tsubo cardiomyopathy. We agree with Dr. Deshmukh concerning the potential value of a national takotsubo cardiomyopathy registry.