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An increased lung to heart ratio(LHR) on thallium-201(Tl- 201) stress myocardial perfusion imaging(MPI) is a predictor of adverse cardiac events and identifies people with extensive coronary artery disease(CAD). The implications of increased LHR in patients undergoing stress technetium- 99m(tc- 99m) sestamibi are developing. Our aim is to evaluate the relationship between increased LHR and extent of CAD in patients undergoing tc- 99m sestamibi MPI. Methods: We reviewed the records and images of 530 consecutive subjects who underwent exercise or adenosine tc- 99 m sestamibi MPI. One hundred thirty-two had transient or partially reversible myocardial perfusion defects and 79(exercise=34, adenosine=45, male=43, female=36, mean age=61 years) of these underwent coronary angiography(study population). The average LHR of these 79 subjects was compared to 79 patients(control population) with normal scans(exercise=50, adenosine=29, male=34, female=45, mean age=60 years). Results: The mean LHR(± SE) in subjects with normal scans was 0.30± 0.01. The mean LHR for those with abnormal scans and single vessel CAD who underwent exercise was 0.32± 0.01 and pharmacological stress was 0.31± 0.01. There was no statistically significant difference between the LHR of those with a normal scan and those with single vessel disease and an abnormal scan. However, there was a statistically significant association between the elevated LHR and multi-vessel CAD. The mean LHR for subjects with multi-vessel CAD with exercise was 0.39± 0.01(p=0.000) and for adenosine was 0.39± 0.02(p=0.000). Conclusion: An elevated LHR in patients undergoing exercise or pharmacological tc- 99m MPI correlates with multi-vessel CAD.