Preoperative monocyte‐to‐HDL‐cholesterol ratio predicts early recurrence after radiofrequency maze procedure of valvular atrial fibrillation

Abstract Background Monocyte‐to‐high‐density lipoprotein (M/H) ratio has emerged as a novel cardiovascular prognostic biomarker. We aimed to evaluate the prognostic values of M/H with early recurrence in persistent valvular atrial fibrillation (AF) patients after radiofrequency (RF) maze procedure. Methods We retrospectively analyzed 131 consecutive persistent AF patients with valvular heart diseases who were followed up 3 months after RF maze procedure. Their clinical data were recorded. Logistic regression analyses were performed for significant predictors. Receiver operating characteristic analysis was used for validation with corresponding area under the curve. Results 70 (53.4%) patients experienced early recurrence after procedure. Patients with early recurrence were older, have longer AF duration history, larger left atria diameter (LAD), higher plasma C‐reactive protein (CRP), lower triglycerides (TG), lower cholesterol (TC), increased monocyte counts, lower HDL cholesterol, and increased M/H ratio. In multivariate analysis, age (OR 1.1 95% CI 1.0‐1.1 P = .003), LAD (OR 2.1, 95%CI 1.2‐3.5, P = .006), TG (OR 0.35, 95% CI 0.15‐0.84, P = .019), M/H (OR 6.1, 95% CI 2.9‐13.0, P < .001) were significantly independent predictors of AF early recurrence. M/H ratio demonstrated a significant predictive value (AUC = 0.77, sensitivity 89.0%, specificity 54%). Further, there was a positive correlation of M/H ratio with CRP and white blood cell. Conclusion Preoperative M/H ratio was an independent risk factor of AF early recurrence following RF maze operation. M/H ratio should be considered in prediction of early recurrence for valvular AF patients.


| INTRODUC TI ON
Atrial fibrillation is the most commonly encountered cardiac arrhythmia in clinical practice, contributing to increased risks of cardiovascular events and adversely affects quality of life. 1 Maze IV procedure based on radiofrequency ablation is widely accepted as an effective treatment for valvular AF. 2,3 Studies suggest that surgical ablation (known as Maze procedure) is superior to drug therapy by increasing the rate of freedom from AF among patients with persistent or long-standing persistent AF. [2][3][4][5] However, the recurrence of AF is common and mostly occurring in the first 3 months after ablation (defined as early recurrence). 6,7 During the first 3 months after surgery, half or more of patients experience atrial arrhythmias. 8 In recent decades, much attention has been dedicated to the clinical importance of early recurrence as it is found to be a powerful independent predictor of late recurrence. [9][10][11] Early restoration of sinus rhythm following ablation deceases adverse atrial remodeling and improves the long-term outcomes. 9 Therefore, it is of great significance to search for preoperative biomarker for early recurrence to avoid procedure-related risks and take early intervention as soon as possible. At the meantime, it is helpful to practice individual therapy to maximize clinical efficacy and to provide insight into more accurate therapies.
Inflammation and oxidative stress are shown to be significant contributors of AF structural remodeling process. 12,13 Various inflammatory biomarkers including CRP, IL-1, IL-6, IL-8, and TNF have been widely studied and demonstrated to be closely associated with electrical and structural atrial remodeling and thrombogenesis in AF. 12 Furthermore, there is a large amount of data showing that oxidative stress has an important role in development of AF. 13,14 Recently, studies suggested that the M/H ratio, which was strongly associated with inflammation and oxidative stress, has emerged as a novel and widely available cardiovascular prognostic biomarker. 15 Canpolat et al evaluated the late recurrence prognostic value of M/H ratio among non-valvular AF patients after catheter ablation. 16 However, its prognostic value of valvular AF early recurrence at 3 months after RF maze procedure remains poorly studied.
Thus, we aimed to investigate the prognostic value of M/H for valvular AF early recurrence at 3 months after RF maze procedure in patients undergoing mitral-valve surgery. Clinical data were collected. Nineteen patients were excluded: 1 case died in hospital; 1 case died of sudden death after discharge; 2 cases died of heart failure after discharge; 3 cases received pacemaker implantation because of long RR intervals or advanced atrioventricular block. Patients who had uncontrolled thyroid dysfunction, pregnancy and subjects with recent infection, malignancies, blood dyscrasias, auto-immune diseases, renal failure, or hepatic failure, current therapy with corticosteroids and non-steroidal anti-inflammatory drugs were excluded from the study. And another six cases were lost at follow-up. Finally, a total of 131 patients eventually achieved complete clinical data and follow-ups.

| Data collection
Baseline characteristics were collected upon admission, including age, sex, smoking and drinking history, body mass index (BMI), medical history, drug use, electrocardiogram (ECG), and transthoracic echocardiography (TTE). Blood samples were collected the first morning of hospitalization and were taken as fasting blood samples to measure preoperative routine blood analyses and a panel of biochemistry markers, including lipid parameters.

| Follow-up
Heart rhythm was continuously monitored after surgery. Dualchamber stimulation at 80 bpm through epicardial temporary pacing wires was used in most of patients for the first 48 hours post-operation to avoid severe brady arrhythmias. Early recurrence was defined as any episode of AF, atrial flutter or atrial tachycardia that lasted greater than 30s in the first 3 month after surgical ablation. 7 Repeat ablation or electronic cardioversion at follow-up time was classified as a recurrence. 7 Patients had scheduled clinical visits. 24hour Holter monitoring was routinely performed in all patients in the first 3 months after surgery. Moreover, patients would receive electrocardiography monitoring in local clinics at any time if they had AF-related symptoms.

| Statistical analysis
All statistical analysis was conducted using SPSS version 22.0 (IBM). Values were presented as median (interquartile range, IQR) and mean ± SD for continuous variables, and proportions for categorical variables. For the comparison between the two groups, Student's t test (normally distributed) or Mann-Whitney test (non-normally distributed) was used for continuous variables, and χ 2 test was utilized for categorical variables. Multivariate logistic regression analysis, which included variables with a P < .05 found on univariate analysis, was performed to identify the predictors of early recurrence. All odds ratios (OR) were given with the 95% confidence interval (CI). A receiver operating characteristic (ROC) curve was used to test the ability of prediction model and the area under the curve (AUC) determined the predictive value.

| RE SULTS
A total of 131 were enrolled in this study. Follow-up was completed in all patients after surgery. The clinical, echocardiographic, and laboratory characteristics of patients with or without early recurrence were comparable reported in Table 1.    Table 3).
In addition, correlation analysis revealed that there was a posi-  Recently, some studies have reported the importance of early recurrence as it is associated with late recurrence, and even is the strongest predictor of late recurrence. [9][10][11] Early intervention for early recurrent AF is associated with excellent long-term outcome. 18 However, there are limited biomarkers available of early recurrence occurred in 3 months in AF patients after RF maze procedure. In present investigation, we showed that M/H level was identified as AF early recurrence marker, and our study find that it has important prognostic value.

| D ISCUSS I ON
Inflammation and oxidative stress, as major contributors to cardiovascular disease, have been implicated as risk factors for AF. [12][13][14] Mediators of the inflammatory response are closely related to electrical and structural remodeling in atria, thereby leading to increased vulnerability to AF. 19 Inflammation also has an effect on calcium homeostasis and connexins, which are associated with triggers of AF and heterogeneous atrial conduction. The activation of fibrotic pathways is also mediated by inflammatory pathways, which can all contribute to structural remodeling of the atria. 12

| Limitations
Of course, the current study has several limitations. First, AF recurrences can be asymptomatic and undetectable. We may underes-

| CON CLUS IONS
Preoperative M/H ratio was an independent risk factor of AF early recurrence following RF maze operation. M/H ratio should be considered in prediction of early recurrence for valvular AF patients.

COMPE TING INTERE S TS
The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

E THI C S APPROVAL AND CON S ENT TO PARTI CIPATE
The current study was approved by the institutional review board of Nanjing Drum Tower Hospital (IRB number 2016-151-01). The requirement to obtain informed consent from the patient was waived.