Detection of coronary artery disease with perfusion stress echocardiography using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radionuclide perfusion imaging.
OBJECTIVE
To determine if perfusion stress echocardiography (PSE) with Imagify (perflubutane polymer microspheres) is comparable to stress perfusion imaging using (99m)Tc single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD.


RESULTS
Chronic, stable, chest pain patients (n=662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha=0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66-71%, P<or=0.004). Four demonstrated non-inferior sensitivity (68-77%, P<or=0.002), three demonstrated non-inferior specificity (72-88%, P<or=0.013). Three PSE readers (RAMP-2) were superior for sensitivity. Two PSE readers (RAMP-1) were superior for specificity. Area under the multi-reader receiver operating characteristics curve (0.72) was equal for both modalities. Majority of adverse events followed dipyridamole dosing, and were mild, transient, and required no treatment.


CONCLUSIONS
Imagify PSE was well-tolerated. Its diagnostic performance in chest pain patients is comparable with SPECT perfusion imaging.
Senior
Roxy
R
Department of Cardiovascular Medicine, Northwick Park Hospital, Watford Road, Harrow, Middlesex HAI 3UJ, UK. roxysenior@cardiac-research.org
Monaghan
Mark
M
Main
Michael L
ML
Zamorano
Jose L
JL
Tiemann
Klaus
K
Agati
Luciano
L
Weissman
Neil J
NJ
Klein
Allan L
AL
Marwick
Thomas H
TH
Ahmad
Masood
M
DeMaria
Anthony N
AN
Zabalgoitia
Miguel
M
Becher
Harald
H
Kaul
Sanjiv
S
Udelson
James E
JE
Wackers
Frans J
FJ
Walovitch
Richard C
RC
Picard
Michael H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D003287:Contrast Media; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging*; D004176:Dipyridamole; D025401:Echocardiography, Stress / Q000379:methods*; D005260:Female; D005466:Fluorocarbons; D015637:Gated Blood-Pool Imaging / Q000379:methods*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D012372:ROC Curve; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055815:Young Adult
D003287:Contrast Media; D005466:Fluorocarbons; D004176:Dipyridamole; C108042:perfluorobutane