BACKGROUND: Ischemic coronary artery disease (CAD) is a major cause for morbidity and mortality resulting in a continuously increasing number of diagnostic interventions. We have validated a new hybrid imaging method using minimized radiation dose for rapid non-invasive prediction of invasive coronary angiography (CA) findings with regard to coronary lesion detection and revascularization. METHODS: Forty patients referred for elective invasive coronary angiography (CA) due to suspected CAD were prospectively enrolled to undergo a low-dose CTCA with prospective ECG-triggering and a stress-only SPECT-MPI scan administering half of the standard low-dose stress (99m)Tc-tetrofosmin activity. The latter was acquired immediately after adenosine stress (omitting the standard 30-60min waiting time). After fusing CTCA and SPECT-MPI decisions towards conservative management versus revascularization strategy based on hybrid images were compared to the decisions taken by the interventional operator in the catheterization laboratory based on CA. The latter served as standard of reference. RESULTS: Hybrid images yielded sensitivity, specificity, positive and negative predictive values and accuracy of 100%, 96.0%, 100%, 93.8% and 97.5% for predicting coronary revascularization. The estimated mean effective radiation doses were significantly lower for hybrid imaging (4.7±1.0mSv) than for invasive CA (8.7±4.2mSv; P<0.001 vs. hybrid). Total non-invasive protocol time was below 60min, comparing favourably to standard SPECT protocols. CONCLUSIONS: Rapid cardiac hybrid imaging allows accurate prediction of invasive CA findings and of treatment decision despite minimized radiation dose and protocol time.