Perflutren-based echocardiographic contrast in patients with right-to-left intracardiac shunts.

septum length, and rims and thickness with electronic caliper edgeto-edge (4). Four main features were used to analyze patients: 1) diameter of the fossa ovalis (FO); 2) presence and length of the channel; 3) presence and degree of atrial septal aneurysm (ASA), following the classification of Olivares et al. (5); and 4) rim thickness. We also analyzed the presence of Eustachian valve and Chiari’s network. We considered eventual additional fenestrations within the fossa as a functional subtype of PFO, despite that, anatomically, they should be considered as secundum atrial septal defects. Thus, combinations of interatrial septum anatomical features were classified into 4 main anatomical subgroups: type 1, small FO, no ASA, short channel, normal rims; type 2, small FO, no ASA, long channel, normal or hypertrophic rims; type 3, large FO, 4 to 5 ASA, short channel, normal or hypertrophic rims; and type 4, large FO, 3 to 5 ASA, multifenestrated, short channel, normal rims (Table 1). FO diameter #20 mm was found to be statistically correlated to the presence of a tunnelized PFO (r 1⁄4 0.91, p < 0.001), whereas FO diameter >25 mm was associated with the presence of ASA (r 1⁄4 0.88, p < 0.001) and a linear correlation between diameter of the FO and ASA severity (the larger the fossa, the more severe the ASA) (r 1⁄4 0.90, p < 0.001). Type 3 anatomical subtype (odds ratio: 4.1 [95% confidence interval: 1.5 to 8.0]; p < 0.001) and type 2 þ Eustachian valve (odds ratio: 4.3 [95% confidence interval: 1.6 to 9.0]; p < 0.001) were the strongest predictors of recurrent ischemic events before transcatheter closure. Our study suggests that the anatomy of the interatrial septum associated with R-to-L shunt is more complex than commonly thought. The combination of the varieties of such anatomical components identifying 4 main anatomic subtypes may help in better clarifying the pathophysiology of paradoxical embolism, which is unlikely to be dominated by 1 factor only, such as ASA, PFO tunnel, or fenestrations. Intriguingly, our data suggest that the FO diameter plays a role in determining the presence of both tunnelized PFO, when the oval fossa is small (<20 mm), and the presence of aneurysm, when the fossa is large ($20 mm). In conclusion, our study showed that in a “real-world” interatrial septum, anatomy greatly differs among patients with R-to-L shunt. The clinical significance of each anatomical pattern seems different: a device closure might be advisable in patients with high-risk anatomical patterns whereas a medical strategy might be adopted in the others.