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Corresponding author at: Department of Cardiac Surgery, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka 565-8565, Japan.
The incidence of late atrial fibrillation (Af) after mitral valve repair was 6% at 5 years and 17.1% at 10 years postoperatively.
•
Small ring annuloplasty, left atrial diameter, and pressure half time in follow-up data were risk factors for late Af.
•
Patients who had late Af developed recurrent mitral insufficiency more frequently than those who did not (p < 0.05).
•
Late Af did not affect long-term survival.
•
Cerebrovascular events occurred relatively more frequently in patients with late Af.
Abstract
Background
There are few reports regarding factors related to late-onset of atrial fibrillation (Af) after mitral valve repair, which can compromise long-term outcome. We analyzed the risk factors for late Af after mitral valve repair.
Methods and results
Between 2001 and 2015, 318 patients (214 males; median, 57.7 years) underwent mitral valve repair for degenerative mitral insufficiency (MI) without concomitant aortic valve disease in our institute. Patients with a history of paroxysmal or chronic Af preoperatively were excluded. Serial follow-up echocardiography was used to evaluate cardiac function. The follow-up rate was 99%. The mean follow-up period was 6.0 ± 4.1 years. There was no early death and there were nine late deaths. A total of 29 (9.1%) patients developed late Af. Freedom from late Af was 94.0% at 5 years and 82.9% at 10 years. Small ring annuloplasty, left atrial diameter, and pressure half time, which were measured at follow-up echocardiography, were considered as significant (p < 0.05) risk factors for late Af. Patients who had late Af developed recurrent MI more frequently than those who did not (p < 0.05).
Conclusions
Remodeling of the atrium caused by functional mitral stenosis is important for late Af, as well as recurrent MI. To prevent these problems, avoiding selection of a small ring at primary mitral repair for type II dysfunction and durable repair are required.
Postoperative atrial fibrillation (Af) is associated with increased morbidity, intensive care unit length of stay, and total length of stay. Af is the most common arrhythmia after cardiac surgery, especially after mitral valve surgery [
Effect of postoperative atrial fibrillation on length of stay after cardiac surgery (the Postoperative Atrial Fibrillation in Cardiac Surgery study [PACS(2)]).
]. The incidence and causes of early onset of postoperative Af before discharge after mitral valve repair have been evaluated. However, the incidence and causes of late-onset postoperative Af after mitral valve repair have seldom been reported [
This study aimed to evaluate the incidence of late onset of Af after mitral valve repair, assess the determinants of late Af, and evaluate the effect of late Af on outcome.
Materials and methods
We performed a retrospective, nonrandomized review of a prospective follow-up of all patients who underwent mitral valve repair because of MI with type II dysfunction. The institutional review board approved the study and granted a waiver of patient consent.
Patients
Between January 2001 and April 2015, 483 patients underwent mitral valve repair for degenerative MI without concomitant aortic valve disease in our institute. After excluding all patients with a history of paroxysmal or chronic Af preoperatively (n = 165, 34.1%), 318 patients were included in this study.
This study included 214 men and 104 women with a mean age of 57.7 ± 12.9 years (range, 19–86 years). Preoperatively, 17 (5.3%) patients were in New York Heart Association functional class III or IV. Postoperatively, all of the patients were followed up at the National Cerebral and Cardiovascular Center or by their personal physicians. Follow-up information was obtained by review of electrocardiograms (ECGs) and consultations that were performed at our institution and at other institutions. We contacted the physicians and institutions participating in the patients’ care and corrected their medical records. All episodes of Af reported here were confirmed by an investigator's review of ECGs or print-outs of telemetry monitoring. Unsubstantiated episodes of palpitation were not considered as Af. Late Af was defined as chronic Af occurring after hospital discharge for primary mitral repair. The follow-up rate was 99% and the mean follow-up period was 6.0 ± 4.1 years. The preoperative patient and hemodynamic characteristics are shown in Table 1.
Table 1Patients’ characteristics and preoperative echocardiographic findings.
All
No Af
Late Af
p-Value
Number of patients
318
289
29
Age (years)
58 ± 13
57 ± 12
63 ± 12
0.016
Male
214 (67.2%)
195 (67.4%)
19 (65.5%)
0.83
BSA (m2)
1.65 ± 0.19
1.65 ± 0.19
1.62 ± 0.19
0.5
NYHA class
1.80 ± 0.5
1.79 ± 0.5
1.89 ± 0.5
0.42
HT
138 (43.3%)
126 (43.5%)
12 (41.3%)
0.66
HL
73 (22.9%)
69 (23.8%)
4 (13.7%)
0.17
DM
31(9.7%)
28 (9.7%)
3 (10.3%)
0.97
FEV1 < 70%
27 (8.4%)
25 (8.6%)
2 (6.8%)
0.7
Creatinine (mg/dl)
0.81 ± 0.22
0.81 ± 0.21
0.83 ± 0.28
0.78
Preoperative β-blocker user
40 (12.5%)
37 (12.8%)
3 (10.3%)
0.68
Preoperative echo findings
MI grade
3.7 ± 0.38
3.7 ± 0.4
3.7 ± 0.3
0.43
LVDd (mm)
58 ± 6.2
58 ± 6.1
58 ± 7.1
0.75
LAD (mm)
47 ± 7.4
47 ± 7.3
50 ± 7.9
0.023
TRPG (mmHg)
30 ± 14.9
30 ± 14.9
34 ± 14.6
0.08
TR
0.8 ± 0.8
0.8 ± 0.8
0.9 ± 0.8
0.45
%FS (%)
39 ± 6.5
38 ± 6.5
39 ± 5.8
0.67
Data are shown as mean ± standard deviation (range) or number (%).
Af, atrial fibrillation; BSA, body surface area; NYHA, New York Heart Association; HT, hypertension; HL, hyperlipidemia; DM, diabetes mellitus; FEV1, forced expiratory volume in 1 second; MI, mitral insufficiency; LVDd, left ventricular end-diastolic diameter; LAD, left atrial diameter; TRPG, tricuspid regurgitant pressure gradient; TR, tricuspid regurgitaiton; %FS, fractional shortening.
The operative data are shown in Table 1. The prolapse area was the posterior leaflet only in 196 patients (61.6%), and the anterior and posterior leaflets, including the commissure (bileaflet), in 122 (38.4%) patients. With regard to valve repair techniques performed in this study, resection and suturing were frequently used for posterior leaflet prolapse and chordal replacement for anterior leaflet prolapse. All (100%) of the patients underwent mitral ring annuloplasty using a prosthetic full ring or partial band. Selection of a prosthetic annuloplasty ring was based on the measurement of the inter-trigon distance using the sizer provided and the same size of prosthesis was selected.
Concomitant cardiac procedures included coronary artery bypass grafting in 24 (7.5%) patients, tricuspid annuloplasty in 18 (5.6%), and other procedures in 14 (4.4%).
Echocardiography
Echocardiography was performed preoperatively, postoperatively, and at follow-up (1, 3, 5, 7, 10, and 15 years after the operation if possible). In patients without Af, the latest follow-up echocardiography was used for analysis, and in patients with late Af, the latest echocardiogram just before the time when they suffered from Af was used for analysis. Doppler echocardiography classified MI grades as follows: 0, none; 1, trivial; 2, mild; 3, moderate; and 4, severe. Severe MI was defined as when Doppler echocardiography detected a central jet with MI of greater than 40% of the left atrial area or a holosystolic eccentric jet with MI, vena contracta greater than 0.7 cm, regurgitant volume greater than 60 mL, regurgitant fraction greater than 50%, or an effective regurgitant orifice greater than 0.40 cm2. The categories of trivial, mild, and moderate MI were graded by an expert engineer and expert doctor individually.
Cardiac function was assessed for every patient, including residual MI, tricuspid regurgitation (TR), fractional shortening, left ventricular end-diastolic diameter and end-systolic diameter, mean transmitral pressure gradient (mPG), pressure half time (PHT), left atrial diameter (LAD), and peak tricuspid regurgitant pressure gradient (TRPG). The LAD from M-mode was measured by a parasternal short-axis image at the level of the aortic valve at ventricular end-systole. TRPG was defined as right ventricular systolic pressure minus central venous pressure (systolic pulmonary artery pressure). Recurrent MI was defined as moderate or severe MI after initial repair.
Statistical analysis
Patient characteristics and preoperative echocardiographic findings shown in Table 1, operative characteristics in Table 2, and follow-up echocardiographic findings and postoperative characteristics in Table 3 were compared by univariate analyses using the χ2 test (for categoric variables) and the Mann–Whitney U test (for continuous variables).
Table 2Operative characteristics.
All (n = 318)
No Af (n = 289)
Late Af (n = 29)
p-Value
Anterior lesion (including bileaflet)
122 (38.4%)
105 (36.3%)
17 (58.6%)
0.018
Posterior lesion only
196 (61.6%)
184 (63.7%)
12 (41.4%)
Resection and suture
253 (79.5%)
233 (80.6%)
20 (68.9%)
0.14
Chordal replacement
85 (26.7%)
72 (24.9%)
13 (44.8%)
0.02
Edge to edge repair
42 (13.2%)
38 (13.1%)
4 (13.7%)
0.92
Partial band
230 (72.3%)
207 (71.6%)
23 (79.3%)
0.37
Ring size (mm)
28.4 ± 1.9
28.5 ± 1.8
27.3 ± 1.7
0.0024
Concomitant with TAP
18 (5.6%)
16 (5.5%)
2 (6.8%)
0.76
Concomitant with CABG
24 (7.5%)
21 (7.2%)
3 (10.3%)
0.54
Operation time (min)
262 ± 65
261 ± 64
275 ± 72
0.25
ECC time (min)
124 ± 42
124 ± 42
127 ± 42
0.54
Arrest time (min)
86 ± 30
85 ± 30
88 ± 29
0.51
Data are shown as mean ± standard deviation (range) or number (%).
Continuous variables are expressed as mean ± SD, and categorical variables as percentages. Freedom from late Af, survival and combined endpoint curves were obtained using the Kaplan–Meier method, and were compared between groups using the log-rank test. Occurrence of late Af was analyzed by censoring at time of death or last follow-up, and the time analyzed was that between surgery and occurrence of Af or last follow-up. The Cox hazard model was used to predict risk factors for late Af. Independent risk factors for late Af were identified by multivariate Cox proportional hazards analysis. Variables with a univariate p-value of <0.05 were entered into the multivariate model. A value of p < 0.05 was considered statistically significant. All statistical analyses were performed using the JMP 11 statistical software package (SAS Institute, Inc., Cary, NC, USA).
Results
The follow-up rate was 99% and the mean follow-up period was 6.0 ± 4.1 years. Twenty-nine patients developed late Af during follow-up. Freedom from late Af at 5 and 10 years was 94.0% and 82.9%, respectively (Fig. 1). Patients’ characteristics and preoperative echocardiographic findings between patients without Af and those with late Af are shown in Table 1. The sex distribution was similar in both groups. A total of 67.4% of the patients without Af were men and 65.5% of the patients with late Af were men (p = 0.83). Patients with late Af were older than those without Af (p = 0.016). Other preoperative findings, including body surface area (BSA), New York Heart Association class, history of hypertension (HT), hyperlipidemia (HL), diabetes mellitus (DM), and forced expiratory volume in one second (FEV1) % < 70% were similar between both groups. Preoperative echocardiographic findings showed that LAD in patients with late Af was significantly larger than that in those without Af (p = 0.023).
Fig. 1Freedom from late Af after mitral valve repair. Twenty-nine patients developed late Af during follow-up. Freedom from late Af at 5 and 10 years was 94.0% and 82.9%, respectively. Af, atrial fibrillation.
Table 2 shows operative characteristics between patients without Af and those with late Af. Patients with late Af had a significantly higher rate of anterior lesions than did those without Af (p = 0.018). Therefore, chordal replacement, which is used for repair of anterior prolapse, was performed more frequently in patients with late Af than in those without Af. The size of the prosthetic ring was significantly smaller in patients with late Af than in those without Af (p = 0.002). There were no significant differences in concomitant tricuspid annuloplasty (TAP), coronary artery bypass grafting (CABG), operation time, extracorporeal circulatory time, and cardiac arrest time between the two groups. There was only 1 patient with surgical left atrial appendage closure.
There were no early deaths and nine late deaths. There were no significant differences in early and late deaths between the two groups. The overall survival rates at 5 and 10 years were 98.3% and 95.4%, respectively. Fig. 2 shows the survival rate between patients without Af and those with late Af. The survival rates at 5 and 10 years were 98.7% and 94.9% in patients without Af, and 96.3% and 96.3% in patients with late Af, respectively, with no significant differences between the groups (p = 0.99).
Fig. 2Survival rate between patients without Af and those with late Af. The overall survival rates at 5 and 10 years were 98.3% and 95.4%, respectively. The survival rates at 5 and 10 years were 98.7% and 94.9% in patients without Af, and 96.3% and 96.3% in patients with late Af, respectively, with no significant differences between the groups (p = 0.99). Af, atrial fibrillation.
Follow-up echocardiographic findings are shown in Table 3. LAD, peak TRPG, mPG, PHT, and TR grade were significantly higher in patients with late Af than in those without Af.
Prescription rate of beta-blocker postoperatively was significantly lower in patients with late Af compared to those without Af (p = 0.008).
During the follow-up period, freedom from recurrent MI was significantly worse in patients with late Af than in those without Af (Fig. 3). Freedom from recurrent MI at 5 and 10 years was 90.2% and 81.7% in patients without Af, and 73.8% and 67.1% in patients with late Af, respectively (p = 0.012). Accordingly, freedom from reoperation between patients without Af and those with late Af was significantly different (Fig. 4). Freedom from reoperation at 5 and 10 years was 97.8% and 96.9% in patients without Af, and 92.7% and 78.6% in patients with late Af, respectively (p = 0.04).
Fig. 3Freedom from recurrent MI between patients without Af and those with late Af. Freedom from recurrent MI at 5 and 10 years was 90.2% and 81.7% in patients without Af, and 73.8% and 67.1% in patients with late Af, respectively, with significant differences between the groups (p = 0.012). Af, atrial fibrillation; MI, mitral insufficiency.
Fig. 4Freedom from reoperation between patients without Af and those with late Af. Freedom from reoperation at 5 and 10 years was 97.8% and 96.9% in patients without Af, and 92.7% and 78.6% in patients with late Af, respectively, with significant differences between the groups (p = 0.04). Af, atrial fibrillation.
Univariate analysis showed that seven variables, including age, ring size, follow-up LAD, follow-up TRPG, follow-up mPG, follow-up PHT, and postoperative prescription rate of β blocker were considered as risk factors for late Af. Among these variables, ring size, follow-up LAD, and follow-up PHT were identified as independent risk factors for late Af in multivariate analysis.
Discussion
In this study, we found that 29 patients developed late Af after mitral valve repair for type II dysfunction during follow-up. Additionally, the incidence of late Af at 5 and 10 years was 6% and 17.1%, respectively. Kernis et al. showed that the incidence of late Af after surgical correction of MI was 12 ± 1% at 5 years and 19 ± 2% at 10 years [
Risk factors for Af are diverse and include advancing age, male gender, diabetes mellitus, cardiovascular disease, post-cardiac surgery, some biomarkers, genetics, etc. [
Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options – a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.
High recurrence of atrial fibrillation in patients with high tissue atrial natriuretic peptide and amyloid levels after concomitant maze and mitral valve surgery.
]. In our study, the mean LAD in patients with late Af was 49 ± 6.9 mm.
A large LAD after mitral valve repair can be caused by either functional mitral stenosis or recurrent MI. In follow-up echocardiographic findings in our study, mPG, PHT, TRPG, and LAD in patients with late Af were significantly higher than those in patients without Af in univariate analyses. Furthermore, in multivariate analyses, PHT and LAD were identified as independent risk factors for late Af. These variables may indicate functional mitral stenosis. In fact, the size of the prosthetic ring was significantly smaller in patients with late Af than in those without Af in multivariate analysis. We have recently shown that a smaller-sized prosthesis can cause functional mitral stenosis at the time of mitral valve repair for type II dysfunction [
]. Additionally, functional mitral stenosis after mitral valve repair may occur in patients who receive small annuloplasty rings with subsequent pannus overgrowth, gradually reducing the mitral valve orifice area over time [
]. Therefore, avoidance of late functional stenosis after mitral valve repair by choosing a larger prosthetic ring is crucial for preventing late Af.
Recurrent MI is also an important factor for developing a large LAD postoperatively. The incidence of recurrent MI was significantly higher in patients with late Af than in those without Af in our study. Freedom from recurrent MI at 5 and 10 years was significantly higher in patients without Af than in those with late Af. Additionally, the incidence of reoperation was significantly higher in patients with late Af than in those without Af.
Reportedly, atrial fibrillation may cause right and left atrial dilatation, leading to mitral annular dilatation and atrial functional MI [
]. However, in our study, recurrent MI in patients with late Af was detected on the latest echocardiogram before they suffered from Af. Accordingly, recurrent MI is considered to be a cause for late Af. Furthermore, David et al. reported that recurrent MI increased the risk of late Af [
]. In our study, we also showed that late Af occurred relatively more frequently in patients with anterior lesion than in patients without Af. Therefore, avoiding recurrent MI, especially in patients with anterior lesions, is crucial for preventing late Af.
Late Af did not affect long-term survival in our study. However, cerebrovascular events including cerebral infarction and transient ischemic attack occurred relatively more frequently in patients with late Af than in those without Af. Therefore, preventing late Af is important for preventing late cerebrovascular events.
In conclusion, functional mitral stenosis is important for late Af in addition to recurrent MI. To prevent these problems, avoiding selection of a small ring at primary mitral repair for type II dysfunction and durable repair are required.
Study limitations
There are several limitations to our study. First, this was a retrospective, observational study. Second, Af was considered to be present only when objectively documented, but it may be transient, and all episodes may not be detected. Therefore, we may have underestimated the incidence of late Af. Additionally, an accurate onset time of Af would be slightly different. This may have biased the results to some degree. Finally, because functional mitral stenosis and recurrent MI after primary mitral repair are time-related in disease progression, a longer follow-up period is required.
Effect of postoperative atrial fibrillation on length of stay after cardiac surgery (the Postoperative Atrial Fibrillation in Cardiac Surgery study [PACS(2)]).
Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options – a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.
High recurrence of atrial fibrillation in patients with high tissue atrial natriuretic peptide and amyloid levels after concomitant maze and mitral valve surgery.
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