OBJECTIVES: The purpose of this study was to understand the reason for variation in the sensitivity of different methods of detecting right-to-left shunts (RLS). BACKGROUND: Patent foramen ovale (PFO) is implicated in the pathogenesis of cryptogenic stroke, decompression illness, and migraine headaches. Intravenous agitated saline injections with tomographic imaging (transthoracic, transesophageal, and intracardiac echocardiography) has been used for detecting intracardiac shunts. Some patients with a high clinical suspicion of PFO have inconclusive echocardiographic study results. Transcranial Doppler (TCD) is an alternative method for detecting RLS that is not dependent on tomographic imaging. METHODS: Thirty-eight consecutive patients who were undergoing PFO closure had simultaneous transcranial Doppler and intracardiac echocardiography performed. Agitated saline injections were performed at rest, with Valsalva maneuver, and with forced expiration into a manometer to 40 mm Hg before and after closure, as well as 3 or more months after closure. Right atrial pressures were measured in the periprocedural period, and RLS were graded according to standard methods during these maneuvers. RESULTS: Right atrial pressures were significantly higher with Valsalva maneuver compared with rest (before closure 21.6 +/- 11.9 mm Hg vs. 6.6 +/- 2.6 mm Hg, p < 0.001; after closure 28.4 +/- 13.9 mm Hg vs. 6.8 +/- 2.6 mm Hg, p < 0.001) and with manometer compared with Valsalva maneuver (before closure 38.7 +/- 6.6 mm Hg vs. 21.6 +/- 11.9 mm Hg, p < 0.001; after closure 44.0 +/- 9.5 mm Hg vs. 28.4 +/- 13.9 mm Hg, p < 0.001). Intracardiac echocardiography underestimated shunting in 34% of patients with Valsalva maneuver or manometer after closure compared with TCD. CONCLUSIONS: Transcranial Doppler with immediate feedback provided by forced expiration against a manometer to 40 mm Hg is more sensitive than echocardiographic imaging for the detection of RLS. These observations have significant implications for determining the incidence of RLS in patients with stroke or migraine.