Transient Ischemic Attack Caused by Contrast Echocardiography in a Patient with Platypnea-Orthodeoxia.
Paul A. Grayburn, M.D.
Main, M. L., S. B. Feinstein, L. M. Feinstein, P. A. Grayburn and S. R. Wilson (2016). “Transient Ischemic Attack Caused by Contrast Echocardiography in a Patient with Platypnea-Orthodeoxia.” Echocardiography 33(1): 165-166.
We read with interest the recent report by Loncar et al. The authors report a case of transient right hemiparesis temporally associated with the intravenous injection of agitated saline microbubbles. The study reportedly revealed “massive passage” of the agitated saline into the left heart in the setting of a large atrial septal aneurysm and two separate atrial septal defects. As the authors note, agitated saline studies have been associated with transient ischemic attacks (TIA), although this is the first report in a patient with platypnea-orthodeoxia. Although the authors reach a broad conclusion regarding risk associated with “contrast echocardiography” in general, they fail to distinguish the known differences between ultrasound contrast agents (UCAs) comprised of agitated saline microbubbles, used in their study, and UCAs that are commercially prepared and FDA-approved. Agitated saline studies utilize significant quantities (~10 mL) of large, unstable, air-filled microbubbles that have no shell and typically are injected with concomitant provocative maneuvers such as Valsalva or cough, aimed at actively potentiating atrial septal passage. In contrast, commercially prepared UCAs consist of very small microspheres (3–4 µm mean diameter) with a narrow size distribution and an encapsulating, biocompatible shell. Commercial UCAs have been approved by regulatory agencies worldwide and act as true intravascular flow tracers. The authors note that commercially available UCAs are contraindicated in patients with right to left shunts, based on theoretical concern for similar neurologic events following administration of these agents. However, the FDA has been asked to rescind the contraindication because it is not based on sound scientific data. In fact, there have been no published reports of ischemic neurologic events attributed to injection of commercial UCAs despite use in millions of patients worldwide, and empiric and experimental observations directly refute the contention that there is any neurologic risk with commercial UCAs. In a recent single-center study of 39 020 patients who were administered commercial UCAs, no TIAs or strokes were found in a subset of 418 patients with known PFOs. Additionally, large registries have reported no neurologic safety signals, despite the fact that based on population statistics, up to ~25% of these patients likely had PFOs. Further, as we have previously noted, FDA guidance regarding UCAs in patients with PFOs is contradicted by FDA’s own labeling for macroaggregated albumin (MAA), which is routinely used in ventilation–perfusion scans of the lungs. MAA has a particle size of 10–90 µm and is potentially capable of occluding arterioles, yet carries only a “warning” for use in patients with PFOs. Recent data indicate that judicious use of commercial UCAs in critically ill patients with baseline technically difficult echocardiograms is associated with lower mortality,[6] perhaps due to earlier and more accurate diagnosis. Withholding UCAs based on discredited theoretical risks is not evidence-based medicine or patient-centered care. The authors should use more specificity when describing “contrast echocardiography” to avoid confusion between agitated saline studies and commercially prepared UCAs that have decidedly different physio-chemical attributes and safety profiles.
