Noncardiac Mechanisms of Right-to-Left Shunting on Contrast-Enhanced Transcranial Doppler: A Narrative Review

Right-to-left shunting detected by contrast-enhanced transcranial Doppler (cTCD) is commonly interpreted as evidence of an intra-cardiac communication such as a patent foramen ovale, often prompting cardiac-focused investigations and management decisions in patients with ischemic stroke or transient ischemic attack. However, cTCD positivity alone is insufficient to localize shunt origin; multiple extra-cardiac mechanisms can generate similar microbubble patterns and lead to diagnostic misclassification. To clarify these alternative pathways, we narratively reviewed the literature from 1980 to 2025 across PubMed, Embase and Scopus, identifying 26 studies in which cTCD was used to evaluate non-cardiac causes of right-to-left shunting, including hepatopulmonary syndrome, pulmonary arteriovenous malformations, physiologic intra-pulmonary shunts, intra-pulmonary arteriovenous anastomoses, extra-cardiopulmonary and extra-hepatic venous anomalies and pressure-dependent pulmonary shunting. Across these conditions, cTCD revealed reproducible physiologic signatures-such as delayed microbubble appearance, prolonged signal duration, temporal dispersion, variable bubble load, limited provocation response and distinct reproducibility patterns-that differ meaningfully from the early, Valsalva-dependent signals typical of isolated intra-cardiac shunts. These findings underscore that cTCD should be interpreted as a dynamic physiologic assessment rather than a binary screening test for cardiac defects. Recognizing the characteristic behaviors of non-cardiac shunts can improve diagnostic precision, reduce the misattribution of stroke mechanisms and support more appropriate, individualized patient management.