Fibrosis, DNA damage-associated reduction in myocardial nuclear density, and advanced atrial amyloidosis are key determinants of atrial dysfunction and impaired postablation functional recovery in patients with AF, and left atrial reservoir strain enables noninvasive identification of advanced atrial amyloidosis.
Key Findings
Results
Left atrial reservoir strain (LASr) improved significantly after catheter ablation in patients who were in AF at the time of echocardiography (Group 2) but not in those in sinus rhythm (Group 1).
Discovery cohort comprised 375 patients with nonvalvular AF undergoing catheter ablation.
Group 1 patients were in sinus rhythm at echocardiography; Group 2 patients were in AF at echocardiography.
Functional recovery was defined as the change in LASr 12 months after ablation.
LASr improved significantly in Group 2 but not in Group 1 following ablation.
Results
Greater fibrosis, reduced myocardial nuclear density, and advanced amyloid deposition were significant determinants of impaired atrial function in both patient groups.
Atrial biopsy samples were quantitatively analyzed for fibrosis, intercellular space expansion, myofibrillar loss, myocardial nuclear density, and amyloid deposition.
Multivariable analyses identified these three histological features as significant determinants of impaired atrial function (all P<0.01).
These findings applied to both Group 1 (sinus rhythm at echocardiography) and Group 2 (AF at echocardiography).
Findings were validated in an independent cohort of 191 patients with AF.
Results
Greater fibrosis, reduced myocardial nuclear density, and advanced amyloid deposition were also significant determinants of limited postablation functional recovery in Group 2 patients.
All three histological features were associated with limited postablation functional recovery specifically in Group 2 (all P<0.01).
Functional recovery was assessed as change in LASr at 12 months after ablation.
Validation was performed in an independent cohort of 191 AF patients.
Results
Advanced atrial amyloid deposition was significantly associated with adverse clinical outcomes.
Amyloid deposition was one of the quantitatively analyzed histological abnormalities from atrial biopsy samples.
Multivariable analyses confirmed the association between amyloid deposition and adverse clinical outcomes (P<0.01).
This finding was observed in both the discovery cohort (n=375) and validated in the independent cohort (n=191).
Results
Decision-tree models incorporating LASr accurately identified advanced atrial amyloid deposition noninvasively in both cohorts.
Decision-tree models using LASr achieved accuracy of 94%–96% for identifying advanced amyloid deposition.
This accuracy was demonstrated in both the discovery cohort and the independent validation cohort.
The finding supports LASr as a noninvasive surrogate marker for advanced atrial amyloidosis.
Results
DNA damage markers were inversely associated with myocardial nuclear density and positively associated with cardiomyocyte hypertrophy.
A subset of atrial biopsy samples was additionally analyzed for DNA damage markers, poly(ADP-ribose), and phosphorylated histone H2A.X.
DNA damage markers showed an inverse association with myocardial nuclear density.
DNA damage markers showed a positive association with cardiomyocyte hypertrophy.
These findings suggest a mechanistic link between DNA damage and the reduction in myocardial nuclear density observed in AF patients.
Background
Atrial fibrillation is associated with diverse histological abnormalities including fibrosis, intercellular space expansion, myofibrillar loss, reduced myocardial nuclear density, and amyloid deposition.
All five histological parameters were quantitatively analyzed from atrial biopsy samples in 375 patients with nonvalvular AF.
The contributions of these histological abnormalities to atrial dysfunction and functional recovery had previously been unclear.
This study provides a systematic quantitative analysis linking specific histological features to echocardiographic measures of atrial function.
What This Means
This research examined tissue samples from the hearts of 375 patients with atrial fibrillation (AF, an irregular heart rhythm) who underwent catheter ablation (a procedure to restore normal rhythm). The researchers looked at five types of microscopic abnormalities in the heart tissue—scarring (fibrosis), cell spacing changes, loss of muscle fibers, reduction in the number of cell nuclei, and deposits of an abnormal protein called amyloid. They then tracked how well the upper chambers of the heart (atria) recovered their pumping function over 12 months after the ablation procedure, measuring function using a specialized ultrasound technique called left atrial reservoir strain (LASr).
The study found that three specific tissue abnormalities—greater scarring, fewer cell nuclei, and advanced amyloid deposits—were the strongest predictors of poor heart function and limited recovery after ablation. Patients whose hearts were in AF at the time of the ultrasound showed meaningful improvement in heart function after ablation, while those already in normal rhythm did not. The researchers also found that DNA damage in heart cells appeared to be linked to the loss of cell nuclei, suggesting a cellular mechanism behind this form of tissue injury. Importantly, amyloid deposits in the atria were associated not just with worse function, but also with worse overall clinical outcomes.
A particularly practical finding was that a simple decision-tree analysis using LASr—a measurement obtainable from a standard echocardiogram without surgery—could identify patients with advanced amyloid deposits with 94–96% accuracy. This suggests that doctors may be able to detect this serious tissue abnormality noninvasively, without requiring a heart biopsy. These findings could help identify patients who are less likely to benefit from catheter ablation and those who may need additional evaluation for atrial amyloidosis.
Takahashi Y, Yamaguchi T, Nakashima K, Shichida S, Otsubo T, Shinzato K, et al.. (2026). Histological Determinants of Atrial Dysfunction in Patients With Atrial Fibrillation.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.051919