Left Atrial Remodeling, Hemodynamic Burden, and Time-Varying Risk of Newly Documented Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction
Marked left atrial enlargement identified a structural-hemodynamic phenotype associated with early documented incident AF and may support risk-enriched rhythm surveillance and may support risk-enriched rhythm surveillance.
Abstract
Background: Left atrial volume index (LAVI) reflects atrial remodeling in heart failure with preserved ejection fraction (HFpEF), but its nonlinear, hemodynamic, and time-varying associations with atrial fibrillation (AF) remain uncertain. Objectives: To assess the association of baseline LAVI with documented incident AF in HFpEF. Methods: We studied 764 patients with HFpEF without documented AF in a Hong Kong registry. LAVI was analyzed continuously, by tertiles, and with restricted cubic splines. Incident AF was the first qualifying AF diagnosis or electrocardiographic record after echocardiography. Cause-specific Cox and Fine-Gray models were used, with death before AF as a competing event. A hemodynamic overlap-adjusted model additionally included E/e' ratio and pulmonary artery systolic pressure. Results: During a median follow-up of 5.81 years, 360 patients developed documented incident AF and 272 died before AF was documented. In the primary clinical model, each 10-mL/m2 increase in LAVI was associated with incident AF in cause-specific Cox regression (HR, 1.08; 95% CI, 1.06-1.11) and Fine-Gray regression (sHR, 1.06; 95% CI, 1.04-1.09). After hemodynamic overlap adjustment, the continuous association was attenuated. However, the highest LAVI tertile remained associated with incident AF (HR, 1.78; 95% CI, 1.28-2.49; sHR, 1.47; 95% CI, 1.05-2.04). Splines showed nonlinear excess risk at higher LAVI, and period-specific analyses showed the strongest association during the first year. Conclusions: Marked left atrial enlargement identified a structural-hemodynamic phenotype associated with early documented incident AF and may support risk-enriched rhythm surveillance.
BACKGROUND
Atrial fibrillation (AF) is a common complication of hypertrophic cardiomyopathy (HCM). Whether left atrial volume index (LAVI) or resting left ventricular outflow tract (LVOT) gradient better identifies patients who develop AF is unresolved.
OBJECTIVES
To compare baseline LAVI and resting LVOT gradient as predictors of incident AF in HCM.
METHODS
We retrospectively studied 777 patients with HCM identified by ICD-10 code I42.1 (obstructive hypertrophic cardiomyopathy). Patients with pre-existing AF or atrial flutter were excluded, leaving 547 patients. The primary exposure was baseline LAVI (available in 167 patients; 25 incident AF events), analyzed per 10-mL/m2 increment. Incident AF was defined as new AF, AF hospitalization, or cardioversion after the index date, and evaluated using Cox models. Secondary analyses assessed LVOT gradient, LAVI tertiles, time-varying mavacamten exposure, and competing risks.
RESULTS
During a median follow-up of 2.31 years, 60 patients developed incident AF. LAVI was independently associated with incident AF in the prespecified model adjusted for age, sex, and hypertension (adjusted HR per 10 mL/m2, 1.27; 95% CI, 1.03-1.57; p = 0.025). AF risk increased across LAVI tertiles (log-rank χ2 = 9.48; p = 0.0087). Resting LVOT gradient was also independently associated with incident AF after the same adjustment (HR per 10 mm Hg, 1.07; 95% CI, 1.00-1.15; p = 0.042; n = 190, 26 events). In a head-to-head model, neither association remained significant.
CONCLUSIONS
In HCM, LAVI and resting LVOT gradient were each independently associated with incident AF, and neither remained significant when modeled together. LAVI may serve as a practical echocardiographic marker to refine AF risk assessment.
Oday Salman, A. Pradeep, Sutopa Purkayastha et al.· Echocardiography· 0 citations
BACKGROUND
Non-invasive assessment of left atrial pressure (LAP) remains difficult in patients with atrial fibrillation (AF). The American Society of Echocardiography (ASE) updated the Recommendations for the Evaluation of Left Ventricular Diastolic Function and introduced a specific algorithm for LAP estimation in AF. We retrospectively investigated the prognostic value of the new algorithm-based LAP assessment in patients with heart failure with preserved ejection fraction (HFpEF) and persistent AF.
METHODS
This study included 363 patients hospitalized for acutely decompensated HFpEF who had persistent AF at discharge. LAP was categorized as normal, elevated, or indeterminate using echocardiography at discharge, according to the algorithm in the 2025 ASE guidelines. Multivariable Cox proportional hazards models were constructed to assess associations between LAP classification and clinical outcomes such as death, heart failure (HF) hospitalization and stroke during follow-up of 574 days.
RESULTS
LAP was classified as elevated in 93 patients (25.6%) and normal in 165 (45.5%), while it was indeterminate in 105 (28.9%) cases due to missing variables recommended in the 2025 guidelines. Elevated LAP was independently associated with HF hospitalization during follow-up period (HR 1.57, 95% CI 1.05-2.37, p=0.03), whereas it was not identified as an independent predictor for death or stroke after adjustment. This association remained significant after accounting for the competing risk of death and was largely preserved across multiple imputation and sensitivity analyses using different assumptions for indeterminate cases. The incremental value of LAP estimation for predicting HF hospitalization over natriuretic peptides was modest and not statistically significant.
CONCLUSIONS
In patients hospitalized for HFpEF with persistent AF, LAP classification was associated with HF hospitalization, implying clinical relevance of the 2025 algorithm-based approach in this challenging population.
K. Iwakura, S. Hoshida, Nobuaki Tanaka et al.· Journal of the American Soci...· 0 citations
INTRODUCTION
Catheter ablation for atrial fibrillation (AF) has been shown to reduce mortality and heart failure (HF) progression in patients with AF and HF with reduced ejection fraction; however, outcomes in HF with preserved ejection fraction (HFpEF), especially the optimal timing of ablation, remain uncertain.
OBJECTIVES
To evaluate long-term outcomes of catheter ablation in patients with AF and HFpEF based on the temporal correlation between the AF diagnosis and the ablation procedure utilizing real-world data.
METHODS
In this observational cohort study using the U.S. Collaborative Network in TriNetX, adults with AF and HFpEF between October 2018 and October 2024 were identified. After 1:1 propensity score matching, 5550 patients were included. The primary endpoint was a composite of cardioversion, new antiarrhythmic drug (AAD) therapy, or repeat AF ablation after a 3-month blanking period. Secondary endpoints included hospitalization, mortality, HF exacerbation, and AAD use up to 4 years of follow-up. Outcomes were compared between patients undergoing ablation within 1 year of AF diagnosis and those having ablation after 1 year.
RESULTS
Over a mean follow-up of 742 ± 489 days, early AF ablation was associated with lower risks of the primary endpoint (hazard ratio (HR) 0.81, 95% CI 0.76-0.87, p < 0.001), reduced hospitalization (HR 0.77, 95% CI 0.70-0.87, p < 0.001), and lower AAD Class I or III use (HR 0.82, 95% CI 0.77-0.88, p < 0.001). No significant differences were observed in HF exacerbations (HR 0.99, 95% CI 0.89-1.00, p = 0.950) or mortality (HR 1.18, 95% CI 0.91-1.53, p = 0.211).
CONCLUSION
Early catheter ablation was associated with a decreased all-cause hospitalization and AF recurrence in HFpEF patients but did not reduce HF exacerbations or mortality.
M. Moersdorf, M. Abou-Khalil, C. El Khoury et al.· Clinical Research in Cardiol...· 0 citations
A
BSTRACT
Chronic left atrial (LA) pressure overload and rheumatic inflammation cause subclinical atrial remodeling even without severe valvular stenosis. This study intended to determine whether advanced atrial deformation parameters identify patients with increased risk of atrial fibrillation (AF) from mild rheumatic mitral stenosis (MS).
A prospective cohort study of patients with mild rheumatic MS and sinus rhythm was conducted in Baghdad, Iraq. LA Reservoir Strain (LASr) and LA Mechanical Dispersion (LAMD) were calculated via two-dimensional strain echocardiography at baseline. Patients were followed up for at least 2 years. The primary outcome was the occurrence of AF.
Of 211 patients, 39 were found to have new-onset AF. The two strain parameters remained independent predictors of new-onset AF on multivariable Cox proportional hazards regression analysis. New AF occurrence was positively correlated with LAMD (adjusted Hazard ratio [aHR]: 1.047 [95% confidence interval (CI): 1.02–1.06],
P
< 0.001) and inversely correlated with LASr (aHR: 0.848 [95% CI: 0.79–0.90],
P
< 0.001). The optimal thresholds for LAMD and LASr for predicting new AF were >58.7 ms and ≤16.6%, respectively, which were defined by the Receiver Operating Characteristic curve.
The presence of subclinical electromechanical dysfunction is an independent predictor of AF in mild rheumatic MS. Recognizing this high-risk phenotype supports closer ambulatory rhythm monitoring to allow timely arrhythmia detection and subsequent initiation of anticoagulation to prevent thromboembolic events.
Diffuse LV interstitial fibrosis quantified by ECV independently predicts incident AF and is associated with adverse atrial remodeling, supporting ventricular fibrosis as an early substrate for AF development.
E. Ebrahimihoor, Elio Salameh, Konstantinos N. Aronis et al.· European Heart Journal-Cardi...· 0 citations
Left atrial (LA) stiffness integrates information related to LA mechanical properties and left ventricular (LV) filling dynamics and may provide a comprehensive assessment of cardiac hemodynamic burden in heart failure (HF). However, its clinical significance in patients with chronic HF and impaired LV systolic function remains unclear. We investigated the association between the LA stiffness index (LASI) and clinical outcomes in patients with chronic HF and impaired LV systolic function. We retrospectively analyzed 1,147 patients with chronic HF and left ventricular ejection fraction (LVEF) <50% who underwent comprehensive echocardiography between January 2018 and March 2023. LASI was calculated as the ratio of E/e' to LA reservoir strain and stratified into tertiles. The primary endpoint was a composite of cardiovascular death or HF hospitalization. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between LASI and clinical outcomes. During a median follow-up of 34 months, 218 patients experienced the primary endpoint. Event-free survival progressively decreased across LASI tertiles (log-rank P < 0.01). After adjustment for age, sex, LVEF, LA volume index, and tricuspid regurgitation velocity, higher LASI remained independently associated with adverse outcomes (hazard ratio 2.41, 95% confidence interval 1.55-3.73, P < 0.01). This association was consistent across clinically relevant subgroups, including age, diabetes mellitus, LV geometry, and LA size. In conclusion, in patients with chronic HF and impaired LV systolic function, increased LASI was independently associated with cardiovascular death and HF hospitalization, suggesting that LASI may serve as a practical echocardiographic marker reflecting atrial dysfunction and hemodynamic burden.
R. Nakayama, Y. Takaya, M. Nakashima et al.· American Journal of Cardiolo...· 1 citation
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