Objectives The objective of this observational study was to compare 48-h all-cause mortality (as well as hospital stay mortality) among critically ill patients who underwent echocardiography either ...with or without an ultrasound contrast agent (UCA). Background The safety of perflutren-based UCAs has been questioned by the U.S. Food and Drug Administration (particularly when administered to critically ill patients) following rare reports of deaths or life-threatening adverse reactions that occurred in close temporal relationship to UCA administration. Methods This was a retrospective observational outcome study conducted in critically ill patients to compare all-cause 48-h and hospital stay mortality subsequent to echocardiography procedures performed either with or without a UCA. The study utilized discharge data from a database maintained by Premier, Inc. (Charlotte, North Carolina). Premier’s database is the largest U.S. hospital–based, service-level comparative database for quality and outcomes research, and provides detailed resource utilization data along with patients’ primary and secondary diagnoses and procedure billing codes. A propensity score–matching algorithm between UCA-enhanced echocardiography patients and non–contrast-enhanced echocardiography patients was utilized to reduce the potential for imbalance in covariates of selected patients in the comparison of mortality between groups. Results Patients undergoing echocardiography with a UCA had lower mortality at 48 h compared with patients undergoing non–contrast-enhanced echocardiography (1.70% vs. 2.50%), with an odds ratio = 0.66 (95% confidence interval CI: 0.54 to 0.80). Patients undergoing echocardiography with a UCA had lower hospital stay mortality compared with patients undergoing noncontrast echocardiography (14.85% vs. 15.66%), with an odds ratio = 0.89 (95% CI: 0.84 to 0.96). Conclusions In critically ill, propensity-matched hospitalized patients undergoing echocardiography, use of a UCA is associated with a 28% lower mortality at 48 h in comparison with patients undergoing non–contrast-enhanced echocardiography. These results are reassuring, given previous reports suggesting an association between UCAs and increased mortality in critically ill patients.
Definity (perflutren lipid microsphere) is an ultrasound contrast agent approved for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the ...delineation of the left ventricular endocardial border. This prospective, open-label, nonrandomized, multicenter, phase 4 surveillance registry study was conducted at 15 clinical sites in the United States and was designed to assess the risk for adverse cardiopulmonary events occurring during or within the initial 30 min after Definity administration in routine clinical practice.
Patients with suboptimal baseline images were consecutively approached regarding study participation. Safety monitoring including vital sign measurements, continuous electrocardiographic monitoring, and continuous oxygen saturation was initiated at baseline before Definity administration and then at regular intervals for 30 min after Definity injection. Patients were assessed for adverse events at 30 min after Definity administration and then contacted by telephone at 24 ± 4 hours to record any subsequent adverse events.
A total of 1,060 patients were enrolled at 15 clinical sites. Of these, 1,053 (99.3%) received at least one dose of Definity and completed the study. No deaths, serious adverse events, or other significant adverse events occurred during this study. The overall adverse event rate was 10.8% (4.5% in patients undergoing rest echocardiography, 13% in patients undergoing rest and exercise stress echocardiography, and 27.7% in patients undergoing rest and pharmacologic stress echocardiography). The overall drug-related adverse event rate (patients with at least one adverse event reported by the principal investigator as related to Definity) was only 3.5%, and most of these (110 of 114 96.5%) were reported by the investigator as mild or moderate in intensity.
Definity is well tolerated in routine clinical practice in patients with a high prevalence of cardiopulmonary disease.
Objectives This was a phase II trial to assess flurpiridaz F 18 for safety and compare its diagnostic performance for positron emission tomography (PET) myocardial perfusion imaging (MPI) with Tc-99m ...single-photon emission computed tomography (SPECT) MPI with regard to image quality, interpretative certainty, defect magnitude, and detection of coronary artery disease (CAD) (≥50% stenosis) on invasive coronary angiography (ICA). Background In pre-clinical and phase I studies, flurpiridaz F 18 has shown characteristics of an essentially ideal MPI tracer. Methods One hundred forty-three patients from 21 centers underwent rest-stress PET and Tc-99m SPECT MPI. Eighty-six patients underwent ICA, and 39 had low-likelihood of CAD. Images were scored by 3 independent, blinded readers. Results A higher percentage of images were rated as excellent/good on PET versus SPECT on stress (99.2% vs. 88.5%, p < 0.01) and rest (96.9% vs. 66.4, p < 0.01) images. Diagnostic certainty of interpretation (percentage of cases with definitely abnormal/normal interpretation) was higher for PET versus SPECT (90.8% vs. 70.9%, p < 0.01). In 86 patients who underwent ICA, sensitivity of PET was higher than SPECT (78.8% vs. 61.5%, respectively, p = 0.02). Specificity was not significantly different (PET: 76.5% vs. SPECT: 73.5%). Receiver-operating characteristic curve area was 0.82 ± 0.05 for PET and 0.70 ± 0.06 for SPECT (p = 0.04). Normalcy rate was 89.7% with PET and 97.4% with SPECT (p = NS). In patients with CAD on ICA, the magnitude of reversible defects was greater with PET than SPECT (p = 0.008). Extensive safety assessment revealed that flurpiridaz F 18 was safe in this cohort. Conclusions In this phase 2 trial, PET MPI with flurpiridaz F 18 was safe and superior to SPECT MPI for image quality, interpretative certainty, and overall CAD diagnosis.
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