The work by Norcliffe-Kaufmann et al published in a recent issue of the American Journal of Cardiology is commendable. The investigators noted excessive pressor responses to cognitive stress, emotional arousal, and hemodynamic stimuli in patients with takotsubo cardiomyopathy (TC), whereas indexes of parasympathetic modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly blunted in TC women compared with controls.

Another striking finding of their study which deserves a clear mention is the low prevalence of diabetes mellitus (DM) in patients with TC. DM prevalence in the study population was only 20% which was much lower compared with the prevalence of other standard cardiac risk factors, namely hypertension (50%) and hyperlipidemia (60%). This finding deserves special attention because the main focus of the study was autonomic function in TC. Similar trends of risk factors in TC have been observed in previous recent small observational studies and also in a large metanalysis. It is hypothesized that the patients with DM may have blunted attenuated sympathetic response because of autonomic neuropathy and blunted catecholamine secretions offering protection to diabetics against the development of TC. Although these data are lacking, one may however speculate that the patients with diabetes who eventually develop TC would be expected to have milder form of DM, or have a serious co-morbidity or overwhelming stress response, outpowering the protective effect of DM. Similarly, long-standing DM, or DM complicated by peripheral or autonomic neuropathy, would offer a setting for an attenuated autonomic response and attenuated sequential injurious influence on the cardiomyocytes.

Similarly, it is plausible that the microvascular damage quantitated by serum cardiac biomarkers in TC would be expected to be somewhat lower in diabetics. The data provided by present study also favor this hypothesis (mean troponin level = 0.92 vs 3.9 ng/ml in diabetics and nondiabetics, respectively). Although it was a small study, it would be interesting to know if the investigators observed any particular differences between the autonomic (sympathetic and parasympathetic) responses in patients with diabetic and nondiabetic TC. The data from future large randomized studies and national and international data registries containing more data about DM in patients with TC would further strengthen our understanding on this subject.