Impact of Unexpected Factors on Quantitative Myocardial Perfusion and Coronary Flow Reserve in Young, Asymptomatic Volunteers

Objectives

We sought to quantify ranges of normal myocardial perfusion and flow reserve in young, asymptomatic volunteers after systematic historical and laboratory screening for unexpected factors affecting coronary flow.

Background

Noninvasive cardiac positron emission tomography (PET) quantifies absolute flow and coronary flow reserve (CFR), thereby defining physiological severity of coronary artery disease for clinical studies or management. Defining “normal” coronary flow is a necessary prerequisite to its broad clinical application.

Methods

Volunteers aged 20 to 40 years of age without cardiac disease or other conditions underwent rest–dipyridamole stress cardiac PET with absolute quantitative flow measurements using Rb-82 in paired studies at least 7 days apart for reproducibility. The presence of coronary calcium, detectable blood nicotine or caffeine, dyslipidemia, and an extended family history of early clinical atherosclerosis were objectively and systematically examined for grouping subjects as true normal or not normal.

Results

We enrolled 125 volunteers, 107 (86%) underwent 2 PET scans. Fifty-six (45%) were classified as true normal, whereas 69 (55%) were classified as not normal. True normals had higher high-density lipoprotein and less PET scan heterogeneity. Hemodynamic responses to dipyridamole stress were similar. Rest flow was the same in both groups (0.72 ± 0.17 ml/min/g vs. 0.69 ± 0.14 ml/min/g, p = 0.164). However, stress flow (2.89 ± 0.50 ml/min/g vs. 2.63 ± 0.61 ml/min/g, p = 0.005) and CFR (4.17 ± 0.80 vs. 3.91 ± 0.86, p = 0.047) were higher in true normals. Paired studies were performed a median of 22 days (interquartile range: 15 to 39) apart. Reproducibility was improved in the true normal group.

Conclusions

One-half of young, asymptomatic volunteers from the community harbor unexpected factors that mildly but systematically reduce stress flow, CFR, and reproducibility. This study establishes normal ranges and reproducibility for flow and CFR as the basis for clinical applications.