According to the study design, we intentionally selected patients without angiographic evidence of post-PTCA LAD restenosis. Worthy of note, the incidence of coronary restenosis was very low 6 months after the procedure, in accord with previous experiences about the combined use of stenting and PTCA [
23]. Nevertheless, 11 our patients without restenosis showed dipyridamole g-SPECT LAD perfusion defects. Myocardial hypoperfusion may occur in patients without overt epicardial coronary artery stenosis having coronary microvessel damage [
24,
25] and coronary microvascular dysfunction corresponds to a reduced CFR in the absence of epicardial coronary stenosis [
26]. Accordingly, the patients of the present study with long-standing SPECT perfusion defects showed lower CFR than the control group. An abnormal CFR had been already described immediately after balloon angioplasty [
5,
27,
28], probably because of a slow recovery of autoregulation in the microvascular bed [
29]. This reduction is primarily due to an increased flow velocity at rest [
5,
27,
28], in relation to the failure of microvessel bed to vasoconstrict appropriately and/or to epicardial vasoconstriction mediated by a myogenic response and/or neural mechanism [
30]. In contrast to previous studies showing normalization of CFR after three [
31], five [
32] or six months [
5], CFR was persistently reduced in our patients with SPECT-derived perfusion defects. A suboptimal Doppler flow wire derived CFR had been observed six months after PTCA without restenosis by DEBATE investigators [
33]. In the suboptimal CFR group the reduction of CFR was mainly due to a long-standing elevation in resting peak velocities while in our patients with perfusion defects it was due to a blunted maximal vasodilator response to dypiridamole. It is conceivable that this alteration could depend on endothelial damage of coronary microcirculation [
34] preceding the procedure and persisting long time after PTCA. Coronary microcirculatory vasoconstriction induced by endothelial dysfunction has been described as effect of spontaneous myocardial ischemia [
35] as well as in conditions other than epicardial coronary artery stenosis, as diabetes mellitus [
36,
37] arterial hypertension [
26,
38] and LV hypertrophy [
39,
40], which can alter microvascular function. However, an alternative interpretation of our findings include the possibility that a residual coronary stenosis might be anatomically insignificant but hemodynamically important, thus explaining a discrepancy between the percentage of lumen reduction and the amount of regional flow reserve.