Dobutamine Stress Cardiac Positron Emission Tomography: Coronary Flow Reserve and Physiologic Targets

Background: Cardiac stress testing with positron emission tomography (PET) is primarily performed with vasodilatory agents such as regadenoson or dipyridamole, however provocative testing with exercise or dobutamine remains a viable alternative. In provocative testing protocols, the stimulus (exercise or dobutamine) is typically given until the patient achieves a percentage (often 85%) of their maximum predicted heart rate (MPHR). This target is based on historical studies of prognosis in traditional exercise stress testing, and not necessarily applicable to myocardial imaging where the goal is augmentation of coronary blood flow to identify flow limiting stenosis. With cardiac PET and absolute myocardial blood flow analysis we are able to quantify the change in myocardial blood flow as the result of stress. We can use these values to explore the relationship between change in heart rate and myocardial blood flow to determine the conditions necessary to identify peak hyperemia and thereby identify flow limiting stenoses. Coronary flow reserve (CFR) is the ratio of stress flow over rest flow, and a marker of the degree of hyperemia obtained as the result of a particular stress agent.

Methods: We evaluated patients who underwent cardiac PET stress testing with dobutamine and measurement of absolute quantitative myocardial blood flow. For each test we recorded the peak heart rate, heart rate as the percentage of maximum predicted heart rate, peak heart rate/rest ratio, stress flow, and coronary flow reserve. Absolute myocardial blood flow was measured in cc/min/gm.

Results: There were 108 patients who underwent cardiac PET stress testing between 2010 and 2018 with dobutamine. Of these patients, 73 (68%) achieved the traditional goal of 85% of their MPHR. CFR was higher in those who achieved 85% MPHR than those who did not (2.97 vs. 2.40 cc/min/gm, p<0.01). Patients were also evaluated by the ratio of their heart rate increase with stress, and 73 patients (68%) achieved a heart rate at stress at least 1.75x their heart rate at rest. When CFR was evaluated in this population, there was a larger difference (3.15 vs. 2.06, cc/min/gm, p<0.000004). Accordingly, the correlation coefficient of CFR/peak-rest heart rate ratio was greater than for CFR/percentage MPHR (R²=0.28 vs. R²=0.0007). Discussion: In this study we demonstrate differences in absolute quantitative myocardial blood flow and CFR as the result of provocative testing. We showed that an increase in myocardial blood flow in stress (CFR) correlated more closely with ratio of heart rate increase in comparison with whether one obtained 85% of their MPHR. This study brings into question whether traditional heart rate goals should be used in provocative stress testing with myocardial imaging, or whether other metrics such as the ratio of heart rate increase which align more closely with the increase in myocardial blood flow should be used.