Relationship Between Left Atrial Diameter And Renal Outcomes In Atrial Fibrillation Patients

2020 European Society of Cardiology（ESC）guidelines for atrial fibrillation（AF）emphasized the importance of integrated management of patients.AF increases the risk of chronic kidney disease（CKD）progression.Previous studies of patients with AF reported the following risk factors were associated with renal function decline:anticoagulation therapy,estimated glomerular filtration rate（eGFR）level,coronary artery disease,old age and CHA₂DS₂-VASc Score.Other studies reported that echocardiographic measures of impaired left ventricular function and increased left atrial diameter（LAD）predict faster renal function decline or progression to dialysis in patients with CKD stages 3-5.Recent studies have found that the enlarged left atrium is an independent risk factor predicting for adverse events,such as stroke,heart failure,recurrence after AF ablation and cardiovascular death.However,no studies have evaluated the association between left atrial diameter and renal outcome in AF patients.The aim was to investigate changes in the eGFR over time and explore the relationship between left atrial enlargement and renal outcomes in real-world patients with atrial fibrillation.Part Ⅰ:Risk factors associated with renal outcome in atrial fibrillation patientsObjective:To investigate the incidence rate of the primary and secondary renal outcome and related risk factors in AF patients.The study examined whether renal function decline was associated with increased risk of bleeding complications.Methods:A total of 5281 patients with AF admitted to the department of cardiology,the Second Affiliated Hospital of Nanchang University,were selected from July 2011 to August 2017 according to inclusion and exclusion criteria.Among them,631patients had eligible follow-up serum creatinine（Scr）data.The baseline demographic characteristics,comorbid conditions,laboratory parameters,medications,echocardiographic data and adverse events（thromboembolic events,Major and/or minor bleeding,and all-cause mortality）during follow-up period were recorded.The eGFR was calculated using the CKD-EPI creatinine equation.We assessed longitudinal changes in the eGFR in our patients during the follow-up.The primary renal outcome was defined as a≥30%decrease from the baseline eGFR.The secondary renal outcome was defined as renal insufficiency（a final eGFR<60ml/min/1.73m² for those with a baseline eGFR≥60 ml/min/1.73m²）.The multivariate logistic regression analysis was used to analyze the risk factors of the primary and secondary renal outcome.Using the Kaplan-Meier method,bleeding free survival curves were plotted and analyzed by log-rank test.Results:1.The overall mean age was 72.3±8.9 years,mean eGFR was 74.4±18.5ml/min/1.73m² and the mean follow-up period was 30.2 months.The primary renal outcome（eGFR decline≥30%）was observed in 155（24.6%）participants during follow-up.The factors associated with≥30%decline in eGFR were proteinuria,heart failure（HF）,persistent AF and LAD≥45 mm（adjusted OR 1.55,95%CI[1.03-2.32],P=0.034）.2.During follow-up,a total of 140 patients had thromboembolic events,44patients had bleeding events（major and/or minor）and 22 patients died of all-cause death.All-cause mortality（9.0%vs.1.7%,P<0.001）and bleedings events（11.6%vs.5.5%,P=0.009）were more commonly observed in patients with the primary renal outcome.There were no significant difference in terms of incidence of thromboembolic events.The Kaplan-Meier curve showed that patients with the primary renal outcome had a higher risk of bleeding.3.Among 478 AF patients with a baseline eGFR≥60 ml/min/1.73m²,137（28.7%）progressed to renal insufficiency（eGFR（27）60 ml/min/1.73m²）.A decreasing eGFR was associated with a lower baseline eGFR（adjusted OR 3.16,95%CI[1.74-5.72],P<0.001）,LAD≥45mm（adjusted OR 2.05,95%CI[1.29-3.27],P=0.003）,HF and age≥75 years.4.During follow-up,16 patients died of all-cause death.A total of 101 patients had thromboembolic events and 32 patients had bleeding events（major and/or minor）.All-cause mortality（6.6%vs.2.1%,P=0.013）and bleedings events（11.7%vs.4.7%,P=0.006）were more commonly observed in patients with the secondary renal outcome.There were no significant difference in terms of incidence of thromboembolic events.The Kaplan-Meier curve showed that patients with renal insufficiency had a higher risk of bleeding.Conclusions:1.Our study demonstrated that proteinuria,HF,persistent atrial fibrillation,and LAD≥45 mm were associated with an eGFR decline≥30%.Bleedings events were more commonly observed in patients with the primary renal outcome;2.LAD≥45mm was also associated with progression to renal insufficiency（eGFR（27）60 ml/min/1.73m²）;3.It was found for the first time that LAD≥45 mm was an independent risk factor for renal function decline,and it may offer an additional predictive factor over conventional clinical parameters in patients with atrial fibrillation.Further research is needed to determine the association between different degrees of left atrial enlargement and renal outcomes.Part Ⅱ: Left atrial enlargement and renal outcome in patients with atrial fibrillationObjective:Left Atrial Enlargement（LAE）has been proven to correlate with clinical adverse events in a variety of disease conditions.Clinical studies have shown that LAE is an independent risk factor for the rapid decline of renal function in CKD patients.The relationship between left atrial size and renal outcome in AF has not been evaluated.Methods:A total of 7200 patients with AF admitted to the department of cardiology,the Second Affiliated Hospital of Nanchang University,were selected from January 2015 to July 2020 according to inclusion and exclusion criteria.Among them,641 patients had eligible follow-up Scr data.Left atrial size was categorized into four groups according to left atrial diameter and gender: normal left atrial size（women,￡38mm;men,￡40mm）（n=308）,mild LAE（women,39-42mm;men,41-46mm）（n=142）,moderate LAE（women,43-46mm;men,47-51mm）（n=97）,and severe LAE（women,≥47mm;men,≥52mm）（n=94）.The renal outcome,which is defined as a ≥30% decline in eGFR in patients with AF.We used Cox proportional hazard models and Kaplan-Meier survival curve to analyze the association of LAE with renal outcome.Results:The overall mean age was 71.0±8.9 years;52.7% were male,36.2% were persistent atrial fibrillation,The mean LA diameter was 40.9±7.7mm.The mean follow-up period was 30.4 months,147 patients（22.9%）were reaching the renal outcome.In multivariable Cox models adjusted for potential confounders,mild LAE（adjusted hazard ratio,1.991;95% confidence interval,1.122 to 3.533）,moderate LAE（adjusted hazard ratio,2.669;95% confidence interval,1.444 to 4.931）and severe LAE（adjusted hazard ratio,2.229;95% confidence interval,1.176 to 4.225）compared with normal LA size were associated with greater risk of renal outcome.LAD as a continuous variable was also associated with greater risk of renal outcome（adjusted hazard ratio 1.055 per 1mm change in LAD,95%CI 1.036 to 1.085）.Conclusions:LAE was an independent risk factor of renal outcome in AF patients,which could be used to stratify patients risk of renal function deterioration and guide early monitor and early intervention.