Safety and positive predictive value of high-dose dipyridamole stress-echocardiography with or without contrast flash-replenishment perfusion imaging in patients with suspected or known coronary artery disease

Abstract

⁎ Corresponding author at: Parma University Hospital, Cardiology Department, Via Gramsci, 14-43100 PARMA, Italy. E-mail address: ngaibazzi@gmail.com (N. Gaibazzi). A growing body of literature has demonstrated the safety of ultrasound contrast agents in conjunction with low mechanical-index imaging during echocardiography, although most studies reported on contrast use during rest echocardiography for left ventricle opacification and rarely on its use during stress-echo (SE) with flash-replenishment myocardial perfusion imaging (MPI). Flash-replenishment sequences, bymeans of high-mechanical index pulses, represent a specificmodel of interaction among ultrasound, microbubbles and myocardial tissue, which could theoretically portend specific safety concerns. We retrospectivelyanalyzedour prospectively collected SEdatabase to evaluate the safetyof a contrast agent (SonoVue©Bracco Imaging Italia srl, Milan, Italy) routinely administered for flash-replenishment high-dose (0.84 mg/kg) dipyridamole echocardiography (cDipSE) and compared this cDipSE groupwith a reference cohortwho underwent standard highdose dipyridamole echocardiography without contrast administration (sDipSE) in the same time frame. According to CTCAE v3.0 standardized terminology (1), moderate (grade 2), severe (grade 3), life-threatening (grade 4) or deadly (grade 5) adverse events (AEs) were recorded during and after SE directly by the physicianperforming the test and after 24 hby contacting the patient. True and false positive figures for coronary artery disease (CAD) detectionwere also calculated in the selected patients who underwent coronary angiography. The database includes 1953 patients who presented between January 2008 and June 2011 and underwent DipSE with (n=1342) or without contrast, (n=611) for suspected or known CAD. Standard DipSE exclusion criteria were used, while pregnancy, knownallergy to sulfonamides or previous anaphylactoid reactions were considered contraindications to contrast administration (cDipSE). The decision to proceed to coronary angiography after DipSE was left to the referring physician, based on clinical judgment and hence influenced by DipSE results. The primary endpoint of the studywas the short-term safety of DipSE (any AENgrade 1 taking place b24 h after the test) and secondarily of sDipSE compared with cDipSE. ContrastDipSE:PatientswhounderwentDipSEwith contrast andflashreplenishment perfusion imaging were 1342; 771 underwent bolus contrast administration,while 571underwent continuous infusion of contrast using a dedicated rotating pump; repeated 0.5 ml boluses (4 to 5 boluses for each test) or infusion at 0.8–1 ml/minute of SonoVue© was used. Myocardial perfusion was studied activating low-MI power-modulation imaging and acquiring flash-replenishment cine-loops in the apical four, three and two-chamber views. Baseline characteristics of the entire DipSE group and of the 2 subgroups based on the use of contrast administration for flash-replenishment perfusion imaging are shown in Table 1. The demographic data and the prevalence of CAD risk factors did not differ significantly between the 2 subgroups, but there were significantly (pb0.001) more abnormal cDipSE than sDipSE—371/ 1342 (28%) vs 55/611 (9%), which was largely expected due to cDipSE taking advantage of wall motion+perfusion imaging analysis. Table 2 reports AEs in the study groups. No fatalities (AEs grade 5) were recorded during the SE study or in the next 24 h. Three lifeTable 1 Baseline clinical characteristics, stress-echocardiography results and coronary angiography data. DipSE = high-dose dipyridamole echocardiography, sDipSE = standard high-dose dipyridamole echocardiography, cDipSE = contrast flash-replenishment dipyridamole echocardiography, CAD = coronary artery disease, MI = myocardial infarction.