Characterization of atrial arrhythmias following mitral valve repair: incidence and risk factors

Objectives: This study aims to investigate the occurrence, type and correlation of early and late atrial arrhythmias following mitral valve repair in patients with no preoperative history of atrial arrhythmias. Methods: Patients undergoing mitral valve (MV) repair for degenerative disease were included. Early and late postoperative electrocardiograms were evaluated for the incidence and type of atrial arrhythmia (atrial fibrillation [AF] or atrial tachycardia [AT]). Results: The 192 patients were included. Early atrial arrhythmias occurred in 100/192 (52.1%) patients; AF in 61 (31.8%) patients, early AT in 15 (7.8%) and both in 24 (12.5%). In total 89% of patients were discharged in sinus rhythm. During a follow ‐ up time of 7.3 years, 14 patients (7.3%) died and 49 (25.5%) patients developed late atrial arrhythmias. At 10 years, the cumulative incidence of any late atrial arrhythmia, with death as competing risk, was 64% (95% confidence interval [CI] = 55% – 72%). On Fine ‐ Gray model analysis, only early postoperative AF lasting >24 h was related to the development of late AF (hazard ratio 5.99, 95% CI = 1.78% – 20.10%, p = .004). Early postoperative ATs were related to the development of late tachycardias, independent of their duration (<24 h hazard ratio 4.25, 95% CI = 1.89 – 9.57, p = .001 and >24 h hazard ratio 3.51, 95% CI = 1.65 – 7.46, p = .001). Conclusions: Early and late atrial arrhythmias were common after MV repair surgery. Only early postoperative AF lasting >24 h was a risk factor for the occurrence of late AF. Conversely, any postoperative AT was correlated to the development of late ATs.

2][3] Following valvular surgery, up to 60% of patients experience early postoperative AAs, with atrial fibrillation (AF) being the most prevalent type. 4,5 addition to AF, patients can experience atrial tachycardias (ATs). 5This may be especially relevant in patients undergoing mitral valve (MV) repair by transseptal approach since the surgical incisions performed at the right atrium and the interatrial septum may facilitate the occurrence of macro-reentrant AT. [6][7][8] Of importance, ATs are not always self-terminating and may expose patients to thromboembolic and bleeding complications. 9,10Moreover, the long-term clinical course of AT may differ from AF.In current literature, limited data on the precise characterization of early and late AAs after MV surgery exists. 11As the pathophysiologic background, clinical consequences and treatment options may differ significantly between different subtypes of AAs, further research is warranted.
To address these knowledge gaps, the aims of the present study were to explore the incidence of early and late AAs following MV repair surgery in patients suffering from MV regurgitation without prior history of AAs, to characterize different types of AAs following MV repair surgery in this patient population and to investigate prognostic factors related to the occurrence and prognosis of AAs.

| Study population
Consecutive adult patients who underwent surgical repair for severe degenerative MV regurgitation between January 2010 and December 2019, at Leiden University Medical Centre, who no documented history of AAs, were included.All available clinical and rhythm documentation before surgery was reviewed.Patient characteristics and details regarding the surgical procedures were collected from patient electronic files and surgical reports.

| Study definitions
AAs were classified as AF or AT.AF was defined as an AA with no discernible repeating P waves and irregular RR intervals, and AT as a sustained regular atrial rhythm with a rate ≥100/min originating from outside the sinus node region. 12,13rly postoperative AF (POAF) and early ATs were defined as events that took place within a period of 30 days after surgery.Late AAs were defined as arrhythmias occurring after this period.For the purpose of this study, both POAF and early ATs were categorized based on their duration and clinical presentation: • Lasting <24 h with either spontaneous termination or after administration of antiarrhythmic drugs, • Lasting >24 h or needing electrical cardioversion.
The diagnosis of AF or AT was based on twelve-lead electrocardiogram (ECG) registrations that were obtained during the postoperative admission period, as well as during follow-up visits in the outpatient clinic.All available rhythm documentation was reviewed by experienced electrophysiologists (M.R.S. and A.P.W.).

| Surgical procedure
The MV was exposed by a transseptal approach, starting with a vertical incision of the right atrium.The type of leaflet repair and annuloplasty device implantation was left at the discretion of the operating surgeon.Anterior MV leaflet prolapse was treated predominantly by implantation of artificial neochords.For posterior MV leaflet prolapse, a combination of chordal replacement and leaflet resection techniques were used.Commissural prolapse was treated by commissural closure, chordal replacement, or papillary muscle head repositioning.
Tricuspid valve repair was performed in the presence of ≥grade 2+ tricuspid regurgitation and/or significant annular dilation.Coronary artery bypass grafting (typically performed in patients with no clinical manifestation of coronary artery disease in whom a significant stenosis was found on preoperative coronary angiography) and other concomitant procedures were performed in accordance to the respective guidelines.The type of concomitant procedures performed did not influence the surgical approach to the MV.

| Postoperative rhythm management
After surgery, continuous cardiac rhythm monitoring was applied using telemetry for the initial five postoperative days.Subsequent to this period, an ECG was performed daily or in case of symptoms suggestive for arrhythmias, until the patients' discharge from the hospital.In the absence of bradycardia, conduction abnormalities or other contraindications, patients were administered sotalol (dosage 120 milligram/day, divided in three doses) for prophylaxis of POAF from postoperative Day 1.If postoperative AAs were observed, the dosage of sotalol was increased.If conversion to sinus rhythm was not achieved within 24 h using medical treatment, electrical cardioversion (ECV) was considered.Postoperative anticoagulation regimen consisted of 3 months of vitamin K antagonist treatment with a target international normalized ratio of 2.0-3.0.Following hospital discharge, heart rhythm surveillance was continued during outpatient clinical follow-ups, utilizing either ECG or Holter, when indicated.
Standard postoperative patient follow-up protocol included outpatient clinic appointments at 1 month, 3 months, and 1 year after the procedure and every 1 year thereafter.

| Study endpoints
The primary endpoint of the study was freedom from any late AAs.
Secondary endpoints were overall survival, freedom from early and late AF and freedom from early and late AT.

| Statistical analysis
Continuous data are presented as mean (standard deviation [SD]) or median and interquartile ranges (IQR).The normality of distribution was tested with the Shapiro-Wilk test.Categorical data are represented as counts and percentages.Overall survival rate was calculated by means of Kaplan-Meier analysis.Between groups differences were estimated with the log-rank test.Cox proportional hazard regression survival analysis was performed to analyse risk factors for mortality.First, a univariable analysis was performed; covariates with a p value of <.10 at univariate analysis were included in the multivariable model with a backward selection method.Early postoperative ATs and POAF were forced into the multivariable model.A competing risk analysis, with death as a competing risk, was performed to estimate the cumulative incidence functions of AAs.
The Fine-Gray model for competing risk analysis was used to identify risk factors for late AF or ATs. 14First, a univariable analysis was performed, including all variables reported in Table I.Covariates with a p value of <.10 at univariate analysis were included in the multivariable model with a backward selection method.Hazard ratios (HR) are reported with 95% confidence intervals (CI).A two-sided p value of <.05 was considered statistically significant.Statistical

| Baseline
Demographic and baseline characteristics are displayed in Table 1.
On adjusted Cox proportional hazard regression survival analysis, POAF was associated with an increased risk of mortality (HR = 6.93, 95% CI = 1.21-39.82,p = .03;Table 2).This was not the case for early ATs (HR = 0.17, 95% CI = 0.20-1.47,p = .11).During follow-up, recurrent mitral regurgitation (≥grade 2+ regurgitation) was seen in 14 patients.Out of these 14 patients, 2 developed late AF and 5 developed late AT.The incidence of AAs in this patient group was comparable to the group of patients who did not develop AAs during follow-up.

| DISCUSSION
In this study, we systematically evaluated the incidence, type, timing and impact on long-term prognosis of AAs after surgical repair for degenerative MV disease.Early AAs were very frequent, affecting >50% of all patients with POAF occurring in 45% of cases and early

| Incidence of early postoperative AA after MV surgery
AAs are frequently observed in the early postoperative phase after MV surgery and their development is attributed to a combination of factors, including a pre-existing atrial substrate, inflammation, cardiac ischemia, alterations in fluid balance/electrolytes and a disbalance in the cardiac autonomic nervous system. 15The addition of atrial scarring by surgical incisions in the right atrium and the interatrial septum, as made in case of a trans-septal approach to the MV, may contribute to the creation of areas of slow conduction and unidirectional conduction block, predisposing to the occurrence of macro-reentry. 16e characterization of postoperative AAs following MV surgery is seldomly reported in the literature and, typically, postoperative AAs are defined as a single entity and not specified as either AF and AT.
However, a comparison study on the clinical course of patients undergoing MV surgery using either the transseptal or left atrial approach, suggested that AAs other than AF might be even more common after MV surgery. 8Consistent with previous findings, a substantial proportion of our patients developed POAF, which emerged as the most prevalent form of early postoperative AAs.The incidence of early ATs observed in our study aligns with previously reported rates. 8Of the POAF episodes lasting >24 h, 50% terminated spontaneously, suggesting a connection solely with transient physiological factors, despite their prolonged duration.Conversely, the remaining half of POAF episodes lasting >24 h did not exhibit spontaneous termination, potentially implicating pre-existing atrial abnormalities capable of sustaining AF for an extended duration.Of all early AT cases lasting >24 h, 65% terminated spontaneously.

| Incidence of late postoperative AAs after MV surgery
To the best of our knowledge, only few studies differentiated between various types of late AAs following MV surgery. 3,8Our results demonstrate that the incidence of late ATs in patients undergoing MV surgery by transseptal approach might be even higher than the incidence of late AF.
In addition to the differentiation between different types of late AAs, we have divided early AAs based on their clinical course early Early ATs were related to the occurrence of late ATs, regardless of the duration and clinical course early after surgery.This comes to little surprise as ATs after MV surgery are more likely related to surgical scars and anatomical structures and are thus related to macro re-entrant pathways.It has previously been shown that right atriotomy incisions can be proarrhythmogenic early after surgery, especially in case of the transseptal approach. 7,16The findings from electrophysiologic studies performed during follow-up provide further support these observations.While only a minority of patients experiencing ATs underwent an ablation procedure, the majority of ATs were right sided, either a cavo-tricuspid isthmus dependent flutter or an intra-atrial re-entrant tachycardia, both facilitated by the introduction of scar by the right atriotomy.
The type of concomitant procedures performed showed no correlation to the occurrence of AAs during follow-up, suggesting a predominant influence of preoperative atrial remodeling and surgical incisions for valve exposure on the occurrence of these AAs.Interestingly, older patient age and male gender were associated with the development of late ATs.These factors can be used to identify patients at particular risk of developing AAs during follow-up after MV surgery.

| Late mortality
Consistent with recent studies, early POAF was associated to a higher risk of late mortality after surgery in our cohort. 17,18Conversely, early postoperative ATs did not exhibit a significant association with late mortality.This discrepancy suggests that early POAF T A B L E 3 Uni-and multivariable Fine-Gray model analysis on predictors of late atrial fibrillation.
analysis was performed using IBM SPSS 23.0 (IBM Corp. Released 2015.IBM SPSS Statistics for Windows) and R version 2023.03.0 (R Foundation for Statistical Computing).

F I G U R E 1
Consort diagram of total mitral valve surgery cohort, exclusions by criteria and the final study cohort.F I G U R E 2 Alluvial plot from inclusion of total study cohort to hospital discharge with results and course of postoperative cardiac arrhythmias.

1 . 5 ( 12 .
29-6.95, p = .011)were related to the development of late ATs.POAF lasting <24 h or >24 h were both not related to the development of late postoperative ATs.Of the 41 patients who developed late ATs during follow-up, 2%) underwent an ablation procedure due to recurrent symptomatic ATs.Of the five patients, (multiple) ATs were inducible in four patients, including a cavo-tricuspid isthmus dependent flutter (n = 2), an intra-atrial re-entrant tachycardia in the right atrium related to the right atriotomy scar (n = 2) and for a focal left sided AT (n = 1).The patient with no inducible AT underwent an empirical cavo-tricuspid isthmus ablation.
Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jce.16390by Cochrane Netherlands, Wiley Online Library on [09/09/2024].See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 15408167, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jce.16390by Cochrane Netherlands, Wiley Online Library on [09/09/2024].See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 3 Cumulative incidence function of freedom from any late postoperative atrial arrhythmias, with death as competing risk.EL MATHARI ET AL. | 5ATs in 20%.Most of these AA's converted spontaneously, some after ECV, resulting in a discharge rate in sinus rhythm of 89%.Late AAs were a common complication within the first 10 years after surgery with late ATs seen more common than late AF.Only POAF lasting >24 h was related to the occurrence late AF, while early postoperative ATs, regardless of their duration, were associated with the occurrence of late ATs.Lastly, POAF was associated with late mortality, while this was not the case for AT.
T A B L E 2 Cox proportional hazard regression survival analysis on risk factors for mortality.
Two models were built, one (I) including only preoperative variables and the other (II) including various types of postoperative AAs.Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jce.16390by Cochrane Netherlands, Wiley Online Library on [09/09/2024].See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License