First of all the authors would like to thank Madias JE for the interest shown in our article . We consider that the questions he raises are highly interesting and deserve further analysis and debate. First, the index of microcirculatory resistance (IMR) is a quantitative and reproducible method for assessing the coronary microvascular function independent of the epicardial arteries. Although the use of high doses of intracoronary nitroglycerine could entail a certain degree of dilatation of larger caliber arterioles, its administration at doses of 100–200 μg during the assessment of coronary microvascular function with IMR is necessary to eliminate any degree of epicardial spasm that could lead to a possible decrease in coronary flow and thus, to a misinterpretation of the microvascular resistance status . Second, myocardial dysfunction in Takotsubo syndrome (TTS) is a consequence of both the effects of the catecholaminergic surge and the coronary microvascular dysfunction present in TTS. The catecholaminergic surge causes a switch from Gs coupling to Gi coupling at the cardiomyocyte β2-adrenergic receptor to limit apoptotic pathways but causing negative inotropic effects , while the inflammatory spikes and the glycocalyx shedding in the early stages of TTS produce an increase in coronary microvascular resistance that enhances myocardial dysfunction . Non-obstructive CAD has also been associated with the presence of endothelial dysfunction and coronary microvascular dysfunction , thus more advanced atherosclerotic disease could lead to more impaired MR in these patients and, in turn, with a higher degree of stunned myocardium and myocardial dysfunction. Therefore, based on the results of our study, we believe that the role of non-obstructive CAD in the development of HF in TTS patients could be a “contributor” rather than just a “red herring”. We hope this adds some clarification to the comments by Madias JE.