Regadenoson induces comparable left ventricular perfusion defects as adenosine: a quantitative analysis from the ADVANCE MPI 2 trial.

OBJECTIVES: This study sought to determine whether regadenoson induces left ventricular perfusion defects of similar size and severity as seen with adenosine stress. BACKGROUND: Total and ischemic left ventricular perfusion defect size predict patient outcome. Therefore, it is important to show that newer stressor agents induce similar perfusion abnormalities as observed with currently available ones. METHODS: The ADVANCE MPI 2 (Adenosine versus Regadenoson Comparative Evaluation for Myocardial Perfusion Imaging) study was a prospective, double-blind, randomized trial comparing image results in patients undergoing standard gated adenosine single-photon emission computed tomography (SPECT) myocardial perfusion imaging who were then randomized in a 2:1 ratio to either regadenoson (N = 495) or a second adenosine SPECT (N = 260). Quantitative SPECT analysis was used to determine total left ventricular perfusion defect size and the extent of ischemia. Quantification was performed by a single observer who was blinded to randomization and image sequence. RESULTS: Baseline gated perfusion results were similar in patients randomized to adenosine or regadenoson. No significant differences in total (11.5 +/- 15.7 vs. 11.4 +/- 15.8, p = 0.88) or ischemic (4.8 +/- 9.2 vs. 4.6 +/- 8.9, p = 0.43) perfusion defect sizes were observed between the regadenoson and adenosine groups, respectively. Linear regression showed a close correlation between adenosine and regadenoson for total (r = 0.97, p < 0.001) and ischemic (r = 0.95, p < 0.001) left ventricular perfusion defects. Serial differences in total (-0.03 +/- 3.89 vs. -0.13 +/- 4.16, p = 0.73) and ischemic (0.15 +/- 4.08 vs. 0.25 +/- 3.81, p = 0.74) perfusion defect size and left ventricular ejection fraction (0.12 +/- 0.32 vs. 0.15 +/- 0.35, p = 0.27) from study 1 to study 2 were virtually identical in patients randomized to regadenoson versus adenosine, respectively. The good correlation between serial adenosine and regadenoson studies regarding total (0.41 +/- 5.43 vs. 0.21 +/- 5.23, p = 0.76) and ischemic (0.17 +/- 5.31 vs. 0.23 +/- 6.08, p = 0.94) perfusion defects persisted in the subgroup of 308 patients with an abnormal baseline SPECT. CONCLUSIONS: Applying quantitative analysis, regadenoson induces virtually identical scintigraphic results as adenosine regarding the size and severity of left ventricular perfusion defects and the extent of scintigraphic ischemia.

Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans.

BACKGROUND: Regadenoson is a selective A2A adenosine receptor agonist and vasodilator used to increase the heterogeneity of distribution of coronary blood flow during myocardial perfusion imaging. This study characterized the dose dependence of regadenoson-induced coronary hyperemia. METHODS AND RESULTS: An open-label, dose-escalation study of regadenoson (10-500 microg, rapid intravenous bolus) was performed in 34 subjects; in 4 additional subjects, the effect of aminophylline to reverse the response to regadenoson was determined. Intracoronary peak blood flow velocity in either the left anterior descending or left circumflex artery was measured by continuous Doppler signal recording, heart rate, central aortic blood pressure, and adverse effects were recorded. Regadenoson increased peak blood flow velocity by up to 3.4-fold in a dose-dependent manner. The mean duration of the increase in flow velocity of 2.5-fold or greater caused by 400 to 500 microg of regadenoson was 2.3 to 2.4 minutes. Regadenoson (400-500 microg) increased heart rate by up to 21 +/- 6 beats/min and decreased systolic blood pressure (-5 +/- 8 mm Hg to -24 +/- 16 mm Hg) and diastolic blood pressure (-8 +/- 4 mm Hg to -15 +/- 14 mm Hg). Aminophylline (100 mg) attenuated the increase in peak flow velocity but not tachycardia caused by 400 microg of regadenoson. CONCLUSION: The results of this study demonstrate the utility of regadenoson as a coronary vasodilator for myocardial perfusion imaging.

Probability models and the applicability of statistical procedures in the identification of chromosomal fragile sites.

Böhm et al. (1995, Human Genetics 95, 249-256) introduced a statistical model (named FSM--fragile site model) specifically designed for the identification of fragile sites from chromosomal breakage data. In response to claims to the contrary (Hou et al., 1999, Human Genetics 104, 350-355; Hou et al., 2001, Biometrics 57, 435-440), we show how the FSM model is correctly modified for application under the assumption that the probability of random breakage is proportional to chromosomal band length and how the purportedly alternative procedures proposed by Hou, Chang, and Tai (1999, 2001) are variations of the correctly modified FSM algorithm. With the exception of the test statistic employed, the procedure described by Hou et al. (1999) is shown to be functionally identical to the correctly modified FSM and the application of an incorrectly modified FSM is shown to invalidate all of the comparisons of FSM to the alternatives proposed by Hou et al. (1999, 2001). Last, we discuss the statistical implications of the methodological variations proposed by Hou et al. (2001) and emphasize the logical and statistical necessity for fragile site identifications to be based on data from single individuals.