A theoretical construct explaining increased right to left shunting instigated by OSA episodes is outlined in Fig. 14.2 with the upper airway obstruction during the initiation of OSA (or Mueller maneuver) leading to a negative intrathoracic pressure which is transmitted to the thin walled atria. Because the right atrium receives venous blood from structures outside of the thorax (inferior and superior vena cava), a strong initial “suction” gradient is created, which leads to increased blood return to the right atrium. The left atrium, however, is supplied by venous return from pulmonary veins which along with their tributaries are located entirely within the thorax and subject to the same negative intrathoracic pressure. Therefore, the left atrium does not receive additional blood return due to the lack of any effective pressure gradient (no “suction” from the pulmonary veins). During the onset of the OSA episode (or Mueller maneuver) when the blood return to the right atrium is greater than that to the left atrium, there would be a resultant abrupt increase in the potential pressure gradient between right and left atrium. In patients with a PFO, this increased gradient would allow for right to left shunting at the atrial level. Of note, the blood return to the right atrium is limited, and is rather quickly depleted due to the collapse of the soft walled great systemic veins (similarly to a collapse of a soft straw on which one sucks too hard, as previously postulated by Condos et al. in 1987 [18]).

Echocardiographic investigation of OSA is limited by the difficulty of obtaining continuous high quality images and measurements during times of sudden intrathoracic pressure changes. This is particularly true with regards to the sudden drop of intrathoracic pressure at the initiation of OSA or Mueller maneuver, which is nearly impossible to image using trans-thoracic echocardiography due to the rapid changes in motion and juxtapositioning of cardiac chambers and intrathoracic structures. Even robust studies conducted in the past using invasive multisensory manometry which aimed at describing the hemodynamic changes typical for the Mueller maneuver (particularly the well conducted study by Condos et al. in 1987 [18]) did not focus on the initial intrathoracic pressure drop but rather reported recordings from the steady state interval following the sudden intrathoracic pressure decline. Therefore, a hemodynamic study, which would precisely measure pressure changes in both atria during the complete Mueller and Valsalva maneuvers was conducted, the results of which showed that the onset of Mueller maneuver increased right-to-left pressure gradient across the atrial septum, and that the pressure gradient across the PFO achieved during Mueller maneuver was greater than that observed during Valsalva maneuver. These findings delineated the possible hemodynamic substrate for right-to-left shunting during OSA.

In light of the common coexistence of PFO and OSA which has been reported in several studies [19–21], it may be reasonable to consider thorough screening for OSA in all patients with PFO and history of thromboembolism or suspected paradoxical embolism. Intervention for these patients with proven OSA would be appropriate, given the other benefits and the benign side effect profile of OSA treatment. However, large prospective trials would be necessary to identify any potential benefit of such approach on the incidence of stroke. Studies evaluating the efficacy of PFO closure for primary or secondary prevention of stroke should consider including OSA as one of the important variables, based on the plausible hypothesis that OSA patients with PFO could potentially benefit from closure more than those without OSA.