We thank Dr. Letić very much for his interest in our report. Dr. Letić observes that it would have been helpful in our report (1) to include some comment about pharmacologic therapy in the control group and not only in the 2 groups of patients with microvascular angina and with “silent” coronary microvascular dysfunction (CMVD), (2) to report the results of coronary angiography in control subjects, and (3) to compare Thrombolysis In Myocardial Infarction (TIMI) frame count (TFC) and exercise stress testing (EST) results in the 3 groups.

As far as the first point is concerned, we would like to stress that in our study, coronary microvascular function was assessed after appropriate withdrawal of medications; accordingly, drugs did not exert any influence on the assessment of CMVD. The reason we underscored in the report that there were no differences in drug therapy between patients with microvascular angina and those with silent CMVD was merely to highlight that the different symptomatic states of these 2 groups could not be related to differences in pharmacologic treatment.

With regard to the second point, control subjects did not undergo coronary angiography. Indeed, they were all asymptomatic and had normal results on maximal EST; thus, there was no clinical indication for and it would have been unethical to perform invasive investigations. According to clinical features, however, controls had a very low probability of obstructive coronary artery disease.

Finally, we agree with Dr. Letić that presenting data on TFC and EST results might have been of some interest. TFC might have provided some clues regarding the possible involvement of microvascular constriction in the mechanisms of CMVD. However, none of our patients had evidence of slow coronary flow on angiography, and basal coronary blood flow velocity in the left anterior descending coronary artery was comparable in the 2 groups of patients with CMVD and in controls, thus suggesting that TFC would have been unlikely to show relevant abnormal findings in these 2 groups of patients.

With regard to EST, patients enrolled in our study had, as an inclusion criterion, consistently positive results on EST, and new EST to correlate the results with coronary microvascular function was not specifically planned for the study. The assessment of ischemic threshold on EST might have provided some evidence of the severity of CMVD in our patients. However, our data clearly already showed that the degree of impairment of coronary microvascular dilation in response to an endothelium-dependent and to an endothelium-independent stimulus was similar in the 2 groups of patients with CMVD.

In summary, we think that assessment of TFC and EST results would not significantly change the main conclusions of our study, which can be summarized as follows: (1) asymptomatic patients with reproducible EST-induced ST-segment depression and angiographically normal coronary arteries may present an impairment of coronary microvascular dilation similar to that found in patients with microvascular angina, and (2) the occurrence or not of symptoms in patients with EST-induced ischemic ST-segment depression related to CMVD can in some way be influenced by differences in the central elaboration of myocardial ischemic signals.