Response to Letter by Tsivgoulis et al
We are thankful to Dr Tsivgoulis and his coauthors for their interest in our article. With regard to their first comment, although we cannot entirely exclude the possibility that an alternative, coincidental source of embolism was present, we consider its likelihood to be minuscule. The patient was monitored with telemetry during her entire hospitalization and at no time had a dysrhythmia, nor did she have a history of dysrhythmic symptoms before or after the index stroke. The writers also suggest that she may not have even had a right to left shunt because her transthoracic echocardiography failed to show one. This is similarly difficult to accept because it is widely acknowledged that transthoracic echocardiography is the least sensitive of all available modalities for detecting a shunt, and the transcranial Doppler (TCD) study findings strongly suggested one. Our statement that “TTE (transthoracic echocardiography) was negative for embolic source and was considered insufficient evidence of PFO (patent foramen ovale)” was intended to mean that a negative TTE was insufficient to rule out a PFO.
Tsivgoulis et al also state, “The authors do not report the results of the TCD study that may assist in elucidating the underlying mechanism of IS (ischemic stroke) in this patient.” The TCD study detected high-intensity transient signals strongly suggestive of a right-to-left shunt, but it was nonrevealing otherwise. In the Table, we described the finding as “possible PFO” because a positive TCD bubble study cannot identify the precise anatomy and location of the shunt.
Tsivgoulis et al imply that a TCD bubble study protocol described in a consensus article is in fact an accepted standard and that the use of the protocol protects against paradoxical air embolism. Although we acknowledge that variations in the technique to perform a bubble study exist between different centers, our experience raises concern about risk. We see no reason why paradoxical air embolism would be less likely to occur during TCD than TTE or transesophageal echocardiography, nor is there published “evidence” that this is the case. The absence of reported cerebral ischemic events does not mean that none are occurring, as we discussed in the article; it is the novel use of the listserve that surfaced these reports because it aggregates rare events.
The purpose of our article is to alert readers about the transient ischemic attack and stroke risk associated with echocardiography and TCD bubble studies. The 5 patients presented in the article exemplify this complication. We wish to emphasize that such a risk can only be properly assessed when these procedures are performed in accordance with a standardized protocol and data are gathered prospectively in the context of a structured study.
J.L.F. is on the speakers bureaus for Bristol Myers Squibb, EKT Pharma, Genentech, and Sanofi-Aventis. B.M.D. is the ESCAPE trial site principal investigator sponsored by St Jude Medical and the RESPECT trial site principal investigator sponsored by AGA. V.L.B. is a consultant for Boston Scientific and is on the speakers bureau for Boehringer Ingelheim. The remaining authors have no conflicts of interest to report.