Quantification of myocardial perfusion in clinical trials

Abstract

In the current era of comparative effectiveness and outcomes research, 1 it is mandatory to have robust estimators of disease, also useful for risk stratification and healthy decision-making.2 Myocardial perfusion imaging with electrocardiographic gated single-photon emission computed tomography (SPECT) is widely used for diagnostic purpose and for risk stratification of patients with suspected or known coronary artery disease.3 However, improving nuclear cardiology practice is required to maximize its role in the presence of multiple concurrent imaging modalities. REGADENOSON SPECT MYOCARDIAL PERFUSION IMAGINGThe United States Food and Drug Administration approved the use of regadenoson, a selective adenosine A2A receptor agonist, on April 10, 2008 for SPECT myocardial perfusion imaging as vasodilator stress agent. 4 In patients undergoing SPECT myocardial perfusion imaging, regadenoson induces an increase in coronary blood flow similar to adenosine. Advantages of regadenoson over adenosine and dipyridamole include its rapid onset of maximal hyperemia (\1 minute), short duration of action, and fixed-dose bolus administration. 5In clinical settings, these advantages translate to a shorter stress protocol and more rapid patient throughput. In addition, regadenoson may be used safely in patients with asthma, chronic obstructive pulmonary disease, and end-stage kidney, and liver disease. Cerqueira et al 7 combined data from two identical double-blind, randomized, active comparator, double dummy, multicenter phase three trials, the ADVANCE MPI (ADenoscan Versus regAdenosoN Comparative Evaluation for Myocardial Perfusion Imaging) 1 and 2 designed to show the strength of agreement between sequential adenosine-regadenoson images. Using visual assessment of serial SPECT images for detection of ischemia relative to adenosine, non-inferiority of regadenoson was demonstrated for all patients and detection of ischemia was also comparable in specific subgroups. However, the average agreement rate between adenosineadenosine and adenosine-regadenoson were 0.62 ± 0.03 and 0.63 ± 0.02 (P = NS). Agreement was less for both agents in women vs men with moderate and large areas of ischemia. This is not surprising based on the significantly greater variability associated with visual as compared to quantitative analysis of SPECT images. 8 In a subsequent study, 9 the same group of investigators used quantitative SPECT analysis to determine the total left ventricular (LV) perfusion defect size and extent of ischemia in patients enrolled in the ADVANCE MPI 2 study randomized in a 2:1 ratio to either regadenoson (n = 495) or a second adenosine SPECT (n = 260) after a standard gated SPECT myocardial perfusion imaging. A single observer who was blinded to randomization and image sequence performed quantification. In this analysis, applying quantitative analysis, regadenoson induced virtually identical scintigraphic results as adenosine regarding the size and severity of LV perfusion defects and the extent of scintigraphic ischemia. In this...