Discussion
This is the first study to show that the LAA ostium reduces in size
after AF ablation, and that this change is markedly asymmetrical, with
the minor axis length shortening significantly more than the major axis
length. In addition, we found that AF patients with HFrEF had a
significantly greater LAA ostium areas than non-HFrEF patients. We also
shown that LAA ostium size was positively correlated with both LA and
LAA volume, and that patients with a “cauliflower” morphology of the
LAA had significantly larger LAA ostia area than patients with other
morphologies. Taking a functional perspective, the LAEF, as well as
total and passive LA strains decreased as the LAA ostium size increased.
LVEF increased significantly after ablation but changes in LVEF after
ablation did not correlation with changes in LAA ostium area after
ablation.
Of all the comorbidities analyzed, only HFrEF correlated significantly
with LAA ostium size. This can be hypothesized to be due to stretching
of the LAA ostium over time secondary to volume overload seen in heart
failure(21). Both LA volume(22) and LAA volume(23) increases in patients
with heart failure, and both LA enlargement(24) and LAA enlargement(25)
is correlated with increased stroke risk. Another consideration
originates from findings of the CASTLE-AF trial, which showed the
superiority of ablation vs. medical therapy among AF patients with
comorbid heart failure (22). The trial showed that the hazard ratio for
stroke in these patients was 0.46 in favor of catheter ablation vs.
medical therapy. This supports our hypothesis that by reducing the LAA
ostial size, catheter ablation is also mitigating stroke risk in this
patient group. Future investigation should further elucidate the
underlying mechanisms for superiority of ablation when compared to
medical therapy in the heart failure population.
When correlating the LAA ostium area to other morphological metrics of
the LA and LAA, we found that the “cauliflower” LAA morphology was
associated with the largest ostial area. Previous studies have found
that “single-lobed”, “cauliflower” LAA morphology and larger LAA
volume was associated with higher rates of stroke (26, 27). This finding
would be supported by the results of our investigation, as a larger LAA
ostium may confer a greater risk for thromboemboli generated in the LAA
of passing into systemic circulation (28). In addition, others have
reported that non- “chicken-wing” LAA morphologies were associated
with higher rates of stroke compared to the “chicken-wing” morphology
(29). However, contradictory findings have also been reported, stating
that stroke rates were similar across patients with different LAA
morphologies (30). Though most studies including ours used a two-expert
consensus in labeling LAA morphology, the relatively subjective nature
of this categorization demands for future revamping and improvement.
In addition to anatomical metrics, various LA functional metrics were
also found to be significantly associated with LAA ostium area.
Specifically, the LAA ostium area was negatively correlated with LAEF,
total LA strain and passive LA strain. While LAEF is more commonly used
as a surrogate for LA function (31), the three components of LA strain
may show a clearer picture and more thoroughly breakdown the role of the
LAA during the normal cardiac cycle and in AF. The total, passive, and
active components of LA strain correspond to the reservoir, conduit and
pumping functions of the LA, respectively (32). Our finding that the LAA
ostium area only correlates with total and passive LA strain may imply
that the LAA is mostly involved in the reservoir and conduit roles of
the atrium, but not necessarily in its pumping function. This is
supported by previous investigations that have characterized the LAA’s
role as an overflow and decompression chamber for the LA (33). It is
also unsurprising that the LAA does not contribute significantly to the
LA pumping function, given its peripheral location, thin walls and
relatively weak contractility (34).
Finally, our study is the first to characterize changes in the LAA
ostium over time after AF ablation. Our hypothesis for the underlying
mechanism includes an ablation-induced chronic remodeling of the left
atrial substrate, which also includes changes to the LAA. The
termination of AF and restoration of sinus rhythm may allow atrial
myocytes to have more regular contractions and higher contractility(35).
Additionally, although there was a near-significant negative correlation
of pre-ablation LVEF and LAA ostium area, there was no direct
correlation found between post-ablation change in LVEF and change in LAA
ostium area. Furthermore, post-ablation change in LAEF also did not
correlate with change in LAA ostium area. These findings suggest that
the reduction in LAA ostium area seen after AF ablation is not a simple,
direct result of functional improvement of the LA or LV. Rather, this
reduction may be due to a more unique remodeling of the LAA in response
to specifically catheter ablation therapy. Interestingly, previous
studies have also found that a LAA ostium size <3.5
cm2 was associated with a reduced risk of stroke(36).
Although we did not find a direct correlation of LAA ostium area with
stroke in our study cohort, 29.7% of our patients did experience a
significant reduction of LAA ostia from >3.5
cm2 to <3.5 cm2. A
prospective, longitudinal study is needed to track stroke incidence in
this group.
Finally, the reduction in LAA ostium area observed in our patient cohort
was markedly asymmetrical, with significantly more shrinkage in the
minor axis length than the major axis length of the centroid. Without a
larger and more comprehensive study, the clinical implications of this
finding remain unclear. Although with the rising popularity of LAA
occlusion devices such as the Watchman™, it may be beneficial to take
these post-ablation changes in the ostia into account when selecting the
appropriate device size. It will also be intriguing to explore the
underlying histology of LA myocytes surrounding the LAA ostium to
determine whether distinct features are present in cells that align in
the minor axis length direction. Lastly, it may be worth investigating
patients whose LAA ostium does not shrink in size after ablation, as
this cohort may exhibit an “ablation-refractory” phenotype and thus
suffer from higher stroke risk despite ablation. For this patient
cohort, LAA occlusion should be considered in addition to standard
anticoagulation therapy to mitigate stroke risk (37).
Our findings bear important and compelling clinical implications that
should be further explored in future investigations. Growing knowledge
of the LAA and the LAA ostium is crucial to our overall understanding of
AF pathophysiology and substrate stratification in AF management.