Incidence and time course of atrial fibrillation following patent foramen ovale closure.

OBJECTIVES: Determine the true incidence and time course of atrial fibrillation (AF) after patent foramen ovale closure (PFOc) using implantable loop recorders (ILR) placed during cryptogenic stroke evaluation. BACKGROUND: Published trials report a 2%-6.6% incidence of postimplant atrial fibrillation (PIAF) after PFOc, which is probably a gross underestimation, as only patients presenting in AF were captured. Episodes of paroxysmal and silent AF would have been missed. METHODS: Of 761 patients who underwent PFOc at a single center between January 2016 and December 2020, 35 patients had an ILR implanted before PFOc, without documentation of AF, and had ≥1 month of monitoring post-PFOc. The incidence, onset, and conclusion of AF episodes were determined from a review of patient records. RESULTS: The mean duration of ILR monitoring was 54.6 ± 39.4 weeks after PFOc. AF occurred in 13/35 (37%) patients. PFOc patients who developed PIAF were older than those who did not (62 ± 11 vs. 52 ± 14 years, p = 0.03). In 12/13, the initial PIAF event occurred within 4 weeks of PFOc, with the greatest frequency around 2 weeks and conclusion by 12 weeks in all. No recurrent strokes occurred during ILR monitoring. CONCLUSION: The actual incidence of PIAF was far greater than previously reported and was significantly associated with older age at PFOc. The timing of PIAF onset and termination were consistent with a postimplant inflammatory mechanism. The higher actual PIAF incidence underscores its low stroke potential in this population. A larger prospective trial is required to validate these preliminary results.

Hypomorphic Smo mutant with inefficient ciliary enrichment disrupts the highest level of vertebrate Hedgehog response.

Smoothened (Smo) is the essential transducer of Sonic hedgehog (Shh) signaling, which regulates cell fate and proliferation during embryogenesis. We identified a novel mouse mutant, cabbie (cbb), and found that its cause is a missense mutation in Smo. We showed the Smocbb mutation is insensitive to the Shh agonist SAG, perhaps due to the disruption of SAG binding. We characterized Smocbb for defects in craniofacial and skeletal development, as well as neural tube patterning, and revealed Smocbb affected processes that require the highest levels of Shh activity. Smo is normally enriched in cilia upon Shh stimulation; however, we detected inefficient enrichment of Smo in Smocbb mutants whether we stimulated with Shh or SAG. Taken together, our data suggest that the highest levels of vertebrate Hedgehog signaling activity require efficient Smo ciliary enrichment.