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Aims: A retrospective study was conducted to correlate the results of myocardial perfusion G-SPECT with clinical evaluation and coronary angiography in the assessment of isolated apical and/or peri-apical reversible perfusion defects. Methods: Coronary angiography was performed in 14 patients (eight males, six females) with isolated apical and/or peri-apical reversible perfusion defects documented on stress myocardial perfusion scintigraphy. Results: Of the eight male patients, seven had > 70% LAD stenosis and one patient had 30% LAD stenosis seen on coronary angiography. Only two of the six female patients (33.3%) had a positive angiogram. In all of the positive angiograms, including those with single, double or triple-vessel disease, the most significant lesion was seen in the LAD artery. Where in addition to the apex, the inferoapical or apicolateral segments were also affected, the culprit stenosis was seen to involve the LAD artery with either normal angiographic appearance or associated less severe stenosis of the right coronary or left circumflex arteries. There was a good correlation between the angiographic and G-SPECT determination of the left ventricular systolic function. Conclusions: Caution should be exercised in the interpretation of isolated apical and/or peri-apical mild reversible perfusion defects in women without stress-induced symptoms and ECG changes, as there is a higher incidence of false-positive MPS studies in this group of patients. In patients with reversible perfusion defects affecting the apex and/or the periapical segments, the most significant stenosis revealed on coronary angiography was found in the LAD artery, independent of the number of diseased coronary arteries.