- Email: [email protected]
Usefulness of Preoperative Atrial Fibrillation to Predict Outcome and Left Ventricular Dysfunction After Valve Repair for Mitral Valve Prolapse
Usefulness of Preoperative Atrial Fibrillation to Predict Outcome and Left Ventricular Dysfunction After Valve Repair for Mitral Valve Prolapse Catherine Szymanski, MDa, Julien Magne, PhDb, Alexandre Fournier, MDa, Dan Rusinaru, MDa, Gilles Touati, MDc, and Christophe Tribouilloy, MD, PhDa,d,* The aim of the study was to assess the impact of atrial fibrillation (AF) on outcome in patients who underwent mitral valve repair (MVRp) for mitral valve prolapse (MVP). Four hundred and forty-three consecutive patients underwent MVRp for organic mitral regurgitation due to MVP. Echocardiography was performed preoperatively and after surgery. Postoperative left ventricular dysfunction (LVD) was defined as left ventricular ejection fraction (LVEF) <50%. Before surgery, 187 patients (42%) had preoperative AF. After surgery, LVEF significantly decreased from 67 – 9% to 56 – 10% (p <0.0001). Compared with patients in sinus rhythm (SR), those in AF were significantly older (p <0.0001), had more severe symptoms (p [ 0.004), had lower LVEF (p [ 0.002), and higher EuroSCORE (p [ 0.05). Compared with patients in SR, patients with AF had significantly lower 10-year survival (64 – 4% vs 83 – 3%, p [ 0.001). On multivariate analysis, preoperative AF was identified as an independent predictor of overall mortality (hazard ratio 1.67; 95% confidence interval 1.15 to 2.42; p [ 0.007). At 10 years, patients with paroxysmal AF had lower survival and higher heart failure rate than patients in SR (78 – 3% vs 66 – 6%) but had a better outcome compared with those with permanent AF (66 – 6% vs 53 – 6%, p [ 0.022). Patients with AF had a significantly higher rate of postoperative LVD (23.3% vs 13.4%, p [ 0.007). In conclusion, preoperative AF is a predictor of long-term mortality and postoperative LVD after MVRp for MVP. To improve postoperative outcome, surgery in these patients should be performed before onset of AF. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;115:1448e1453) Atrial fibrillation (AF) is a common arrhythmia in conservatively managed organic chronic mitral regurgitation (MR).1,2 Previous studies have reported that the prevalence of AF in patients who underwent mitral valve surgery varies from 20% to 55%.3e6 It is widely accepted that, when feasible, mitral valve repair (MVRp) is the procedure of choice in patients with severe organic MR. The current American College of Cardiology/American Heart Association (ACC/AHA)1 and European Society of Cardiology (ESC)2 guidelines recommend surgery in the presence of symptoms or left ventricular dysfunction (LVD)/dilatation (class I recommendation).1 Mitral surgery may also be considered when patients have developed AF. Thus, the occurrence of AF is an ACC/AHA and ESC class IIa recommendation with a low level of evidence (B and C respectively). Actually, conflicting data have been reported regarding the impact of preoperative AF on outcome after mitral valve surgery.7 In a Mayo Clinic study including
Departments of aCardiology and cCardiac Surgery, University Hospital Amiens, Amiens, France; bDepartment of Cardiology, University of Liege, CHU Sart Tilman, Liège, Belgium; and dINSERM U1088, University of Picardie, Amiens, France. Manuscript received December 27, 2014; revised manuscript received and accepted February 13, 2015. See page 1453 for disclosure information. *Corresponding author: Tel: (þ33) 3-22-45-58-83; fax: (þ33) 3-22-4556-58. E-mail address: [email protected] (C. Tribouilloy). 0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.02.027
patients with degenerative mitral valve prolapse (MVP) in sinus rhythm (SR) at baseline, an increase in cardiac mortality after onset of AF was observed under conservative management.8 Conversely, some data have shown that preoperative AF had no significant impact on early or late mortality after MVRp.4,7 Moreover, the impact of preoperative AF (i.e., permanent or paroxysmal) on the risk of cardiac postoperative LVD has been suggested.3 The present study sought to analyze in patients who underwent MVRp for MVP (1) the prognostic value of preoperative permanent and paroxysmal AF on long-term mortality and (2) the association between preoperative AF and occurrence of LVD. Methods From January 1, 1991, to December 31, 2012, 443 consecutive patients who underwent MVRp for organic MR because of leaflet prolapse at our institution were included in this study. All patients had complete preoperative and postoperative echocardiographic evaluation. Preoperative echocardiography was defined as echocardiography performed 3 months before surgery, and postoperative echocardiography was defined as echocardiography performed 9 to 12 months after surgery. Exclusion criteria were (1) MR caused by ischemic heart disease or dilated cardiomyopathy, rheumatic heart disease, active infective endocarditis, and congenital heart disease; (2) previous cardiac surgery; (3) concomitant aortic valve or aortic root surgery; (4) patients with history of myocardial www.ajconline.org
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Table 1 Preoperative and operative characteristics of the population according to the presence of preoperative atrial fibrillation Characteristics
Age (years) Men NYHA I II III IV Height (cm) Weight (kg) Heart rate (bpm) Logistic EuroSCORE Hypertension Diabetes mellitus Echocardiography data Left atrial diameter (mm) LV end-diastolic diameter (mm) LV end-systolic diameter (mm) Ejection fraction (%) MR grade II III IV Prolapse site Anterior Posterior Both leaflets Pulmonary artery systolic pressure * (mmHg) Therapy Angiotensin receptor blockers Angiotensin conversion enzyme inhibitors Beta blockers Digoxin Warfarin Antiplatelet Calcium blocker Diuretic Amiodarone Cardiopulmonary bypass time (minutes) Aortic cross clamp time (minutes) Concomitant coronary bypass
Overall study population
Sinus rhythm
Atrial fibrillation
(n¼443)
(n¼256)
(n¼187)
65.4 11.1 316 (71.3%)
63.1 11.5 191 (74.6%)
68.5 9.7 125 (66.8%)
51 (11.5%) 174 (39.3%) 162 (36.6%) 56 (12.6%) 170.8 8.8 74.6 14.6 75.3 16.0 3.2 3.6 168 (38.3%) 29 (6.6%)
35 (13.7%) 113 (44.1%) 84 (32.8%) 24 (9.4%) 171.1 8.5 75.0 13.9 74.0 13.8 3.0 3.0 95 (37.7%) 15 (6.0%)
16 (8.6%) 61 (32.6%) 78 (41.7%) 32 (17.1%) 170.4 9.2 74.0 15.6 77.2 18.5 3.6 4.2 73 (39.0%) 14 (7.5%)
49.3 61.3 36.8 67.3
8.6 6.6 6.9 9.1
47.4 61.2 36.2 68.5
7.3 6.2 6.7 8.9
51.5 61.4 37.6 65.7
9.5 7.2 7.2 9.2
p value
<0.0001 0.074 0.004
0.481 0.552 0.062 0.050 0.775 0.522 <0.0001 0.745 0.057 0.002 0.375
5 (1.1%) 170 (39%) 261 (59.9%)
3 (1.2%) 106 (41.7%) 145 (57.1%)
2 (1.1%) 64 (35.2%) 116 (63.7%)
27 (6.1%) 307 (69.3%) 109 (24.6%) 46.4 14.6
14 (5.5%) 381 (70.7%) 61 (23.8%) 45.9 14.7
13 (7.0%) 126 (67.4%) 48 (25.7%) 46.9 14.4
0.538
27 (6.6%) 232 (56.4%) 132 (31.9%) 73 (17.6%) 156 (36.8%) 82 (20.1%) 82 (20.2%) 158 (38.3%) 65 (16.0%) 135.6 40.3 94.7 25.2 56 (12.7)
15 (6.5%) 126 (54.3%) 68 (29.2%) 5 (2.1%) 23 (9.6%) 43 (18.2%) 42 (17.9%) 79 (33.2%) 26 (11.1%) 135.941.5 94.5 24.2 33 (12.9)
12 (6.7%) 106 (59.6%) 64 (35.4%) 68 (37.6%) 133 (71.9%) 39 (22.7%) 40 (23.4%) 79 (45.4%) 39 (22.8%) 135.2 38.7 95.0 26.5 23 (12.3)
0.941 0.267 0.181 <0.0001 <0.0001 0.277 0.171 0.012 0.002 0.872 0.832 0.841
0.701
LV ¼ left ventricular; NYHA ¼ New York Heart Association. * Data available in 354 patients (80%).
infarction or recent acute coronary syndrome; and (5) patients with concomitant maze procedure or any surgical treatment of AF. Baseline clinical characteristics, co-morbidity, symptoms, and operative data were collected from patients’ medical records. The standard logistic EuroSCORE9 was calculated retrospectively for each patient using the calculator available online at www.euroscore.org. All patients underwent preoperative electrocardiogram, and chronic and paroxysmal AF were defined as recommended by current ACC/AHA guidelines.10 Institutional review board authorization was obtained before initiation of the study. The study was conducted in accordance with institutional policies, national legal requirements, and the revised Declaration of Helsinki. Diagnoses of leaflet
prolapse and flail leaflets were identified according to the recommended criteria.11 LV dimensions were assessed from parasternal long-axis views by 2-dimensionaleguided M-mode using the leading edge methodology at enddiastole and end-systole. Left ventricular ejection fraction (LVEF) was estimated by the Simpson biplane method or visually.12 Preoperative LVD was defined as an LVEF <60%. Two-dimensional echocardiography-guided diameter12e14 was measured with M-mode at end-systole in the parasternal long-axis view, according to the method proposed by the American Society of Echocardiography.14 Pulmonary artery systolic pressure was estimated using the simplified Bernoulli equation (4 tricuspid valve regurgitation velocity) plus the estimated right atrial pressure.
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Figure 1. Kaplan-Meier overall survival rate in the whole population: 88 2% and 74 2% at 5 and 10 years, respectively.
Study end points were perioperative mortality, overall mortality (i.e., including perioperative and mortality after hospital discharge), postoperative LVD (defined as LVEF <50%), and a composite of all-cause death and heart failure. Perioperative mortality was defined as death occurring within 30 days after surgery or longer if the patient was hospitalized for a longer duration. Mean duration of followup was 8.7 5.3 years (median: 8.6 years; twenty-fifth to seventy-fifth percentiles: 4.4 to 12.5 years). During followup, patients were monitored by their personal general practitioners or cardiologists. Events were ascertained by review of medical records and clinical interviews or by telephone calls to physicians, patients, and (when necessary) next of kin. Normally distributed continuous variables were expressed as mean SD. Categorical variables were summarized as frequency percentages and absolute numbers. Comparisons between groups were performed with the Student t tests or chi-square tests, as appropriate. Variables not normally distributed were expressed as median (interquartile range). Survival curves were plotted according to the Kaplan-Meier method, and differences between groups were compared with the log-rank test. For multivariate analyses, an epidemiologic approach was adopted, and the following variables were entered in multivariate analyses: New York Heart Association class, logistic EuroSCORE, and preoperative AF. Multivariate logistic regression analysis was performed to evaluate predictors of postoperative LVD. Multivariate Cox proportional hazard analyses were performed to investigate predictors of death during followup. A p value of 0.05 was considered significant for all statistical tests. Data were analyzed with SPSS 17.0 (SPSS Inc., Chicago, Illinois). Results Posterior leaflet prolapse was the most common mitral valve abnormality (69%, n ¼ 307), 6% of patients had anterior leaflet prolapse (n ¼ 27), and 25% (n ¼ 109) had
Figure 2. Kaplan-Meier overall survival rate according to the presence of preoperative AF (permanent or paroxysmal AF) compared with SR: 93 2% and 83 3% in patients with SR versus 81 3% and 64 4% in patients with AF, respectively, at 5 and 10 years (p ¼ 0.001) (panel A); Kaplan-Meier overall survival rate according to the presence of preoperative permanent AF, paroxysmal AF, or SR: 93 2% and 83 3% in patients with SR versus 84 4% and 70 6% in patients with paroxysmal AF versus 80 4% and 59 6% in patients with permanent AF, respectively, at 5 and 10 years (p <0.0001) (panel B).
prolapse involving both leaflets. Thirteen percent of patients (n ¼ 56) had associated coronary artery bypass graft surgery. Demographic, clinical, and echocardiographic data according to the presence of preoperative AF are presented in the Table 1. One hundred eighty-seven patients (42%) had preoperative AF. These patients were significantly older, had a higher logistic EuroSCORE, greater left atrial (LA) diameter, and lower LVEF than patients in SR. Patients with AF also had more severe symptoms. Digoxin,
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Figure 4. Frequency of postoperative LVD (defined by a postoperative LVEF <50%), in patients with SR, paroxysmal AF, and permanent AF.
Figure 3. Kaplan-Meier event-free survival (death or cardiac heart failure) rate according to the presence of preoperative AF (permanent or paroxysmal AF) compared with SR: 88 2% and 78 3% in patients in SR versus 76 3% and 59 4% in patients with AF, respectively, at 5 and 10 years (p ¼ 0.001) (panel A); Kaplan-Meier event-free survival (death or cardiac heart failure) rate according to the presence of preoperative permanent AF, paroxysmal AF, or SR: 88 2% and 78 3% in patients with SR versus 81 4% and 66 6% in patients with paroxysmal AF versus 72 5% and 53 6% in patients with permanent AF, respectively, at 5 and 10 years, (p <0.0001) (panel B).
warfarin, and amiodarone were prescribed significantly more frequently in patients with AF (Table 1). Of the 187 patients with preoperative AF, 101 had permanent AF and 86 had only paroxysmal AF. Compared with those with paroxysmal AF, patients with permanent AF were significantly older (71 9 vs 66 9 years, p ¼ 0.001), had higher logistic EuroSCORE (4.3 5.3 vs 2.9 2.4, p ¼ 0.024), greater LA diameter (54 10 vs
48 9 mm, p ¼ 0.001), higher heart rate (82 22 vs 72 13 beats/min, p ¼ 0.001), and lower LVEF (64 10% vs 68 8%, p ¼ 0.007). The perioperative mortality rate (2%, n ¼ 9) was similar between patients with preoperative AF and those in SR (2.7% vs 1.6%, p ¼ 0.41). Overall, 117 deaths (26.5%) occurred during follow-up resulting in 10-year overall survival of 74 2% (Figure 1). Among the 187 patients with preoperative AF, 66 died during follow-up (25 had paroxysmal AF before surgery and 41 presented permanent AF). In univariate analysis, postoperative 10-year overall survival was significantly better in patients in SR compared with those with AF (Figure 2). On multivariate analysis, AF (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.15 to 2.42; p ¼ 0.007) was identified as an independent predictor of postoperative overall mortality. Further adjustment for LVEF (HR 1.75, 95% CI 1.20 to 2.53; p ¼ 0.003), LV end-systolic diameter (1.81, 95% CI 1.22 to 2.68; p ¼ 0.003), or coronary artery bypass (HR 1.68, 95% CI 1.16 to 2.43; p ¼ 0.006) did not influence this independent relation. The 10-year overall survival in patients with permanent AF and in those with paroxysmal AF was significantly lower compared with patients in SR (both p <0.0001) (Figure 2). However, in patients with AF, postoperative overall survival in patients with permanent AF compared with those with paroxysmal AF tended to be lower (p ¼ 0.091). The combined end point of overall mortality and postoperative heart failure resulted in better 10-year event-free survival in patients in SR than in those with AF (Figure 3). On multivariate analysis, AF (HR 1.61, 95% CI 1.15 to 2.26; p ¼ 0.005) was identified as an independent predictor of combined postoperative overall mortality and heart failure. Further adjustment for LVEF (HR 1.68, 95% CI 1.20 to 2.36; p ¼ 0.003), LV end-systolic diameter (HR 1.68, 95% CI 1.18 to 2.40; p ¼ 0.004), or coronary artery bypass (HR 1.62, 95% CI 1.16 to 2.28; p ¼ 0.005) did not influence this independent relation. The 10-year event-free survival (overall mortality and postoperative heart failure) in patients with permanent AF and in patients with paroxysmal AF was significantly lower compared with those in
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SR (both p <0.0001) (Figure 3). Among patients with AF, 10-year postoperative event-free survival was lower in patients with permanent AF compared with patients with paroxysmal AF (p ¼ 0.022). Among asymptomatic patients (n ¼ 51), there were 35 patients in SR and 16 patients in AF. There were no deaths at follow-up in patients in SR, whereas 5 asymptomatic patients died during follow-up in the AF group. Postoperative overall survival was significantly better in asymptomatic patients in SR compared with those with AF (10-year overall survival of 100% vs 77 12%; p ¼ 0.002). The combined end point of overall mortality and postoperative heart failure resulted in better 10-year event-free survival in asymptomatic patients in SR than in those with AF (100% vs 71 12%; p <0.0001). Patients with preoperative AF compared with those in SR had higher rates of postoperative LVD (23.3% [n ¼ 42] vs 13.4% [n ¼ 33]; p ¼ 0.007; Figure 4). Univariate analysis identified preoperative AF as a predictor of postoperative LVD (odds ratio [OR] 1.87, 95% CI 1.13 to 3.09; p ¼ 0.015). After adjustment by EF, preoperative AF (OR 1.79, 95% CI 1.06 to 3.02; p ¼ 0.03) remained associated with postoperative LVD. Discussion The present study shows that, in patients with organic MR due to MVP and who underwent MVRp, preoperative AF is (1) common (42% of cases), (2) a powerful predictor of long-term postoperative overall mortality and combined postoperative overall mortality and heart failure, and (3) a predictor of postoperative LVD. Furthermore, although patients with paroxysmal AF had a better outcome compared with those with permanent AF, these paroxysmal patients with AF had lower survival than those in SR. Previous studies have reported discordant results concerning the impact of preoperative AF after MVRp on outcome. A retrospective single-center study4 including 323 patients reported no significant difference in terms of 5-year survival between patients with AF and those in SR. However, this study included patients with various causes of primary MR and concomitant aortic valve operation and many patients with coronary artery disease, which may at least partially explain the different results compared with those of our study. Jessurun et al7 in a series, which included not only patients with MVP but also patients with endocarditis, and even mitral stenosis and rheumatic valve disease, reported no significant survival difference between patients with preoperative SR and paroxysmal or permanent AF. However, the investigators showed that the persistence of AF after surgery appeared to be associated with lower survival. Lim et al15 in a series, including a high proportion of patient with rheumatic MR in the AF group, reported that AF affected survival only in univariate analysis but not in multivariate analysis with no distinction between paroxysmal and permanent AF. In line with our results, Eguchi et al6 showed that patients with preoperative AF had a poorer outcome after MVRp, suggesting that mitral surgery should preferably be performed before onset of AF. These data are consistent with those of the Mayo Clinic study showing that onset of AF during conservative
management of patients with AF was associated with increased mortality and morbidity.8 Our results also demonstrated that the outcome of patients with AF is worse than in patients with SR. Furthermore, our results showed a difference in outcome according to the type of AF (i.e., chronic vs paroxysmal) with an excess of overall mortality or heart failure in patients with permanent AF compared with patients with paroxysmal AF. However, despite the excess of overall mortality or heart failure in patients with paroxysmal AF compared with those with SR, patients with paroxysmal AF had better outcome compared with those with permanent AF. Importantly, we showed that preoperative AF was also a predictor of postoperative LVD. Moreover, preoperative pulmonary hypertension and AF in patients who underwent MVRp increased by almost twofold the risk of postoperative LV dysfunction.3 Therefore, waiting for the onset of AF results in excessive postoperative mortality and morbidity (i.e., heart failure and LVD), and the onset of AF must be considered as a decisive turning point in the course of MR because of MVP. In patients presenting for mitral valve surgery with chronic AF, according to guidelines, treatment by a maze procedure should be considered, but the increased morbidity related to this procedure should also be considered. In our series, the 3 patients treated by a maze procedure or other surgical treatments of AF during mitral surgery were excluded to avoid introducing any factor that could influence the postoperative onset of AF. Decision making in the treatment of patients with AF and organic severe MR is complex. When performed at the appropriate time, surgical correction of chronic organic MR should theoretically restore normal LV function16 and geometry and life expectancy. AF is a frequent complication in these patients3e6,17 observed with a frequency of 42% in our population. The presence of AF is currently a class IIa indication for surgery in patients with no distinction between permanent and paroxysmal AF.1,2 Although both American and European guidelines emphasize that new onset of AF constitutes a strong argument for surgery in asymptomatic patients with MR (classes IIaB and IIaC respectively), few data and no obvious proof are available in the literature, and therefore, the level of evidence of these recommendations remains B and C. Accordingly, we reported an excess of mortality, heart failure, and postoperative LVD when patients are operated after onset of AF (even if AF is only paroxysmal). As AF is associated with a worse postoperative outcome, our data strongly suggest that, in the presence of severe MR because of MVP, the first sign of AF (i.e., chronic or paroxysmal) must be considered to be an indication of prompt surgery. The present study was a retrospective analysis of patients’ records and, therefore, has the inherent limitations of such analyses. If these data are confirmed by further prospective studies, they may lead to revision of the current class IIa recommendation2 toward a class I recommendation regarding patients with paroxysmal or permanent AF and severe MR due to MVP with a high probability of durable MVRp. Ideally, MVRp should be considered while patients are still in SR, before onset of AF. Actually, the main determinant of onset of AF in patients with primary MR is LA
Valvular Heart Disease/Atrial Fibrillation Impact on Mitral Regurgitation
dilation. LA diameter or LA volume is helpful for risk stratification of these patients, even when they are asymptomatic.18,19 Therefore, serial measurements of LA dimensions during follow-up may be useful for decision making in patients in SR and to determine optimal timing of surgery for these patients. Thus, in the absence of documented AF, surgery could be discussed in asymptomatic patients with severe organic MR due to MVP with a high probability of MVRp and very low operative risk but presenting obvious LA dilation (indexed LA volume >60 ml/ m2)19 as suggested by the ESC recommendations (class IIbC recommendation).2
9. 10.
Disclosures The authors have no conflicts of interest to disclose. 1. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP III, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM III, Thomas JD; Members AATF. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 2014;129:e521ee643. 2. Joint Task Force on the Management of Valvular Heart Disease of the European Society of C; European Association for Cardio-Thoracic S, Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schafers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33: 2451e2496. 3. Varghese R, Itagaki S, Anyanwu AC, Milla F, Adams DH. Predicting early left ventricular dysfunction after mitral valve reconstruction: the effect of atrial fibrillation and pulmonary hypertension. J Thorac Cardiovasc Surg 2014;148:422e427. 4. Chua YL, Schaff HV, Orszulak TA, Morris JJ. Outcome of mitral valve repair in patients with preoperative atrial fibrillation. Should the maze procedure be combined with mitral valvuloplasty? J Thorac Cardiovasc Surg 1994;107:408e415. 5. Bando K, Kasegawa H, Okada Y, Kobayashi J, Kada A, Shimokawa T, Nasu M, Nakatani S, Niwaya K, Tagusari O, Nakajima H, Hirata M, Yagihara T, Kitamura S. Impact of preoperative and postoperative atrial fibrillation on outcome after mitral valvuloplasty for nonischemic mitral regurgitation. J Thorac Cardiovasc Surg 2005;129:1032e1040. 6. Eguchi K, Ohtaki E, Matsumura T, Tanaka K, Tohbaru T, Iguchi N, Misu K, Asano R, Nagayama M, Sumiyoshi T, Kasegawa H, Hosoda S. Pre-operative atrial fibrillation as the key determinant of outcome of mitral valve repair for degenerative mitral regurgitation. Eur Heart J 2005;26:1866e1872. 7. Jessurun ER, van Hemel NM, Kelder JC, Elbers S, de la Riviere AB, Defauw JJ, Ernst JM. Mitral valve surgery and atrial fibrillation: is atrial fibrillation surgery also needed? Eur J Cardiothorac Surg 2000;17:530e537. 8. Grigioni F, Avierinos JF, Ling LH, Scott CG, Bailey KR, Tajik AJ, Frye RL, Enriquez-Sarano M. Atrial fibrillation complicating the course
11.
12.
13.
14.
15. 16.
17. 18.
19.
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of degenerative mitral regurgitation: determinants and long-term outcome. J Am Coll Cardiol 2002;40:84e92. European System for Cardiac Operation Risk Evaluation. Available at: http://www.Euroscore.Org. 2011. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG; American College of Cardiology; American Heart Association; European Society of Cardiology; North American Society of Pacing, Electrophysiology. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European Society of Cardiology Committee for practice guidelines and policy conferences (committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 2001;22: 1852e1923. Levine RA, Stathogiannis E, Newell JB, Harrigan P, Weyman AE. Reconsideration of echocardiographic standards for mitral valve prolapse: lack of association between leaflet displacement isolated to the apical four chamber view and independent echocardiographic evidence of abnormality. J Am Coll Cardiol 1988;11:1010e1019. Quinones MA, Waggoner AD, Reduto LA, Nelson JG, Young JB, Winters WL Jr, Ribeiro LG, Miller RR. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography. Circulation 1981;64:744e753. Tribouilloy C, Grigioni F, Avierinos JF, Barbieri A, Rusinaru D, Szymanski C, Ferlito M, Tafanelli L, Bursi F, Trojette F, Branzi A, Habib G, Modena MG, Enriquez-Sarano M; Investigators M. Survival implication of left ventricular end-systolic diameter in mitral regurgitation due to flail leaflets a long-term follow-up multicenter study. J Am Coll Cardiol 2009;54:1961e1968. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in m-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58: 1072e1083. Lim E, Barlow CW, Hosseinpour AR, Wisbey C, Wilson K, Pidgeon W, Charman S, Barlow JB, Wells FC. Influence of atrial fibrillation on outcome following mitral valve repair. Circulation 2001;104:I59eI63. Tribouilloy C, Rusinaru D, Szymanski C, Mezghani S, Fournier A, Levy F, Peltier M, Ben Ammar A, Carmi D, Remadi JP, Caus T, Touati G. Predicting left ventricular dysfunction after valve repair for mitral regurgitation due to leaflet prolapse: additive value of left ventricular end-systolic dimension to ejection fraction. Eur J Echocardiogr 2011;12:702e710. Obadia JF, el Farra M, Bastien OH, Lievre M, Martelloni Y, Chassignolle JF. Outcome of atrial fibrillation after mitral valve repair. J Thorac Cardiovasc Surg 1997;114:179e185. Rusinaru D, Tribouilloy C, Grigioni F, Avierinos JF, Suri RM, Barbieri A, Szymanski C, Ferlito M, Michelena H, Tafanelli L, Bursi F, Mezghani S, Branzi A, Habib G, Modena MG, Enriquez-Sarano M; Mitral Regurgitation International DI. Left atrial size is a potent predictor of mortality in mitral regurgitation due to flail leaflets: results from a large international multicenter study. Circ Cardiovasc Imaging 2011;4:473e481. Le Tourneau T, Messika-Zeitoun D, Russo A, Detaint D, Topilsky Y, Mahoney DW, Suri R, Enriquez-Sarano M. Impact of left atrial volume on clinical outcome in organic mitral regurgitation. J Am Coll Cardiol 2010;56:570e578.
Departments of aCardiology and cCardiac Surgery, University Hospital Amiens, Amiens, France; bDepartment of Cardiology, University of Liege, CHU Sart Tilman, Liège, Belgium; and dINSERM U1088, University of Picardie, Amiens, France. Manuscript received December 27, 2014; revised manuscript received and accepted February 13, 2015. See page 1453 for disclosure information. *Corresponding author: Tel: (þ33) 3-22-45-58-83; fax: (þ33) 3-22-4556-58. E-mail address: [email protected] (C. Tribouilloy). 0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.02.027
patients with degenerative mitral valve prolapse (MVP) in sinus rhythm (SR) at baseline, an increase in cardiac mortality after onset of AF was observed under conservative management.8 Conversely, some data have shown that preoperative AF had no significant impact on early or late mortality after MVRp.4,7 Moreover, the impact of preoperative AF (i.e., permanent or paroxysmal) on the risk of cardiac postoperative LVD has been suggested.3 The present study sought to analyze in patients who underwent MVRp for MVP (1) the prognostic value of preoperative permanent and paroxysmal AF on long-term mortality and (2) the association between preoperative AF and occurrence of LVD. Methods From January 1, 1991, to December 31, 2012, 443 consecutive patients who underwent MVRp for organic MR because of leaflet prolapse at our institution were included in this study. All patients had complete preoperative and postoperative echocardiographic evaluation. Preoperative echocardiography was defined as echocardiography performed 3 months before surgery, and postoperative echocardiography was defined as echocardiography performed 9 to 12 months after surgery. Exclusion criteria were (1) MR caused by ischemic heart disease or dilated cardiomyopathy, rheumatic heart disease, active infective endocarditis, and congenital heart disease; (2) previous cardiac surgery; (3) concomitant aortic valve or aortic root surgery; (4) patients with history of myocardial www.ajconline.org
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Table 1 Preoperative and operative characteristics of the population according to the presence of preoperative atrial fibrillation Characteristics
Age (years) Men NYHA I II III IV Height (cm) Weight (kg) Heart rate (bpm) Logistic EuroSCORE Hypertension Diabetes mellitus Echocardiography data Left atrial diameter (mm) LV end-diastolic diameter (mm) LV end-systolic diameter (mm) Ejection fraction (%) MR grade II III IV Prolapse site Anterior Posterior Both leaflets Pulmonary artery systolic pressure * (mmHg) Therapy Angiotensin receptor blockers Angiotensin conversion enzyme inhibitors Beta blockers Digoxin Warfarin Antiplatelet Calcium blocker Diuretic Amiodarone Cardiopulmonary bypass time (minutes) Aortic cross clamp time (minutes) Concomitant coronary bypass
Overall study population
Sinus rhythm
Atrial fibrillation
(n¼443)
(n¼256)
(n¼187)
65.4 11.1 316 (71.3%)
63.1 11.5 191 (74.6%)
68.5 9.7 125 (66.8%)
51 (11.5%) 174 (39.3%) 162 (36.6%) 56 (12.6%) 170.8 8.8 74.6 14.6 75.3 16.0 3.2 3.6 168 (38.3%) 29 (6.6%)
35 (13.7%) 113 (44.1%) 84 (32.8%) 24 (9.4%) 171.1 8.5 75.0 13.9 74.0 13.8 3.0 3.0 95 (37.7%) 15 (6.0%)
16 (8.6%) 61 (32.6%) 78 (41.7%) 32 (17.1%) 170.4 9.2 74.0 15.6 77.2 18.5 3.6 4.2 73 (39.0%) 14 (7.5%)
49.3 61.3 36.8 67.3
8.6 6.6 6.9 9.1
47.4 61.2 36.2 68.5
7.3 6.2 6.7 8.9
51.5 61.4 37.6 65.7
9.5 7.2 7.2 9.2
p value
<0.0001 0.074 0.004
0.481 0.552 0.062 0.050 0.775 0.522 <0.0001 0.745 0.057 0.002 0.375
5 (1.1%) 170 (39%) 261 (59.9%)
3 (1.2%) 106 (41.7%) 145 (57.1%)
2 (1.1%) 64 (35.2%) 116 (63.7%)
27 (6.1%) 307 (69.3%) 109 (24.6%) 46.4 14.6
14 (5.5%) 381 (70.7%) 61 (23.8%) 45.9 14.7
13 (7.0%) 126 (67.4%) 48 (25.7%) 46.9 14.4
0.538
27 (6.6%) 232 (56.4%) 132 (31.9%) 73 (17.6%) 156 (36.8%) 82 (20.1%) 82 (20.2%) 158 (38.3%) 65 (16.0%) 135.6 40.3 94.7 25.2 56 (12.7)
15 (6.5%) 126 (54.3%) 68 (29.2%) 5 (2.1%) 23 (9.6%) 43 (18.2%) 42 (17.9%) 79 (33.2%) 26 (11.1%) 135.941.5 94.5 24.2 33 (12.9)
12 (6.7%) 106 (59.6%) 64 (35.4%) 68 (37.6%) 133 (71.9%) 39 (22.7%) 40 (23.4%) 79 (45.4%) 39 (22.8%) 135.2 38.7 95.0 26.5 23 (12.3)
0.941 0.267 0.181 <0.0001 <0.0001 0.277 0.171 0.012 0.002 0.872 0.832 0.841
0.701
LV ¼ left ventricular; NYHA ¼ New York Heart Association. * Data available in 354 patients (80%).
infarction or recent acute coronary syndrome; and (5) patients with concomitant maze procedure or any surgical treatment of AF. Baseline clinical characteristics, co-morbidity, symptoms, and operative data were collected from patients’ medical records. The standard logistic EuroSCORE9 was calculated retrospectively for each patient using the calculator available online at www.euroscore.org. All patients underwent preoperative electrocardiogram, and chronic and paroxysmal AF were defined as recommended by current ACC/AHA guidelines.10 Institutional review board authorization was obtained before initiation of the study. The study was conducted in accordance with institutional policies, national legal requirements, and the revised Declaration of Helsinki. Diagnoses of leaflet
prolapse and flail leaflets were identified according to the recommended criteria.11 LV dimensions were assessed from parasternal long-axis views by 2-dimensionaleguided M-mode using the leading edge methodology at enddiastole and end-systole. Left ventricular ejection fraction (LVEF) was estimated by the Simpson biplane method or visually.12 Preoperative LVD was defined as an LVEF <60%. Two-dimensional echocardiography-guided diameter12e14 was measured with M-mode at end-systole in the parasternal long-axis view, according to the method proposed by the American Society of Echocardiography.14 Pulmonary artery systolic pressure was estimated using the simplified Bernoulli equation (4 tricuspid valve regurgitation velocity) plus the estimated right atrial pressure.
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Figure 1. Kaplan-Meier overall survival rate in the whole population: 88 2% and 74 2% at 5 and 10 years, respectively.
Study end points were perioperative mortality, overall mortality (i.e., including perioperative and mortality after hospital discharge), postoperative LVD (defined as LVEF <50%), and a composite of all-cause death and heart failure. Perioperative mortality was defined as death occurring within 30 days after surgery or longer if the patient was hospitalized for a longer duration. Mean duration of followup was 8.7 5.3 years (median: 8.6 years; twenty-fifth to seventy-fifth percentiles: 4.4 to 12.5 years). During followup, patients were monitored by their personal general practitioners or cardiologists. Events were ascertained by review of medical records and clinical interviews or by telephone calls to physicians, patients, and (when necessary) next of kin. Normally distributed continuous variables were expressed as mean SD. Categorical variables were summarized as frequency percentages and absolute numbers. Comparisons between groups were performed with the Student t tests or chi-square tests, as appropriate. Variables not normally distributed were expressed as median (interquartile range). Survival curves were plotted according to the Kaplan-Meier method, and differences between groups were compared with the log-rank test. For multivariate analyses, an epidemiologic approach was adopted, and the following variables were entered in multivariate analyses: New York Heart Association class, logistic EuroSCORE, and preoperative AF. Multivariate logistic regression analysis was performed to evaluate predictors of postoperative LVD. Multivariate Cox proportional hazard analyses were performed to investigate predictors of death during followup. A p value of 0.05 was considered significant for all statistical tests. Data were analyzed with SPSS 17.0 (SPSS Inc., Chicago, Illinois). Results Posterior leaflet prolapse was the most common mitral valve abnormality (69%, n ¼ 307), 6% of patients had anterior leaflet prolapse (n ¼ 27), and 25% (n ¼ 109) had
Figure 2. Kaplan-Meier overall survival rate according to the presence of preoperative AF (permanent or paroxysmal AF) compared with SR: 93 2% and 83 3% in patients with SR versus 81 3% and 64 4% in patients with AF, respectively, at 5 and 10 years (p ¼ 0.001) (panel A); Kaplan-Meier overall survival rate according to the presence of preoperative permanent AF, paroxysmal AF, or SR: 93 2% and 83 3% in patients with SR versus 84 4% and 70 6% in patients with paroxysmal AF versus 80 4% and 59 6% in patients with permanent AF, respectively, at 5 and 10 years (p <0.0001) (panel B).
prolapse involving both leaflets. Thirteen percent of patients (n ¼ 56) had associated coronary artery bypass graft surgery. Demographic, clinical, and echocardiographic data according to the presence of preoperative AF are presented in the Table 1. One hundred eighty-seven patients (42%) had preoperative AF. These patients were significantly older, had a higher logistic EuroSCORE, greater left atrial (LA) diameter, and lower LVEF than patients in SR. Patients with AF also had more severe symptoms. Digoxin,
Valvular Heart Disease/Atrial Fibrillation Impact on Mitral Regurgitation
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Figure 4. Frequency of postoperative LVD (defined by a postoperative LVEF <50%), in patients with SR, paroxysmal AF, and permanent AF.
Figure 3. Kaplan-Meier event-free survival (death or cardiac heart failure) rate according to the presence of preoperative AF (permanent or paroxysmal AF) compared with SR: 88 2% and 78 3% in patients in SR versus 76 3% and 59 4% in patients with AF, respectively, at 5 and 10 years (p ¼ 0.001) (panel A); Kaplan-Meier event-free survival (death or cardiac heart failure) rate according to the presence of preoperative permanent AF, paroxysmal AF, or SR: 88 2% and 78 3% in patients with SR versus 81 4% and 66 6% in patients with paroxysmal AF versus 72 5% and 53 6% in patients with permanent AF, respectively, at 5 and 10 years, (p <0.0001) (panel B).
warfarin, and amiodarone were prescribed significantly more frequently in patients with AF (Table 1). Of the 187 patients with preoperative AF, 101 had permanent AF and 86 had only paroxysmal AF. Compared with those with paroxysmal AF, patients with permanent AF were significantly older (71 9 vs 66 9 years, p ¼ 0.001), had higher logistic EuroSCORE (4.3 5.3 vs 2.9 2.4, p ¼ 0.024), greater LA diameter (54 10 vs
48 9 mm, p ¼ 0.001), higher heart rate (82 22 vs 72 13 beats/min, p ¼ 0.001), and lower LVEF (64 10% vs 68 8%, p ¼ 0.007). The perioperative mortality rate (2%, n ¼ 9) was similar between patients with preoperative AF and those in SR (2.7% vs 1.6%, p ¼ 0.41). Overall, 117 deaths (26.5%) occurred during follow-up resulting in 10-year overall survival of 74 2% (Figure 1). Among the 187 patients with preoperative AF, 66 died during follow-up (25 had paroxysmal AF before surgery and 41 presented permanent AF). In univariate analysis, postoperative 10-year overall survival was significantly better in patients in SR compared with those with AF (Figure 2). On multivariate analysis, AF (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.15 to 2.42; p ¼ 0.007) was identified as an independent predictor of postoperative overall mortality. Further adjustment for LVEF (HR 1.75, 95% CI 1.20 to 2.53; p ¼ 0.003), LV end-systolic diameter (1.81, 95% CI 1.22 to 2.68; p ¼ 0.003), or coronary artery bypass (HR 1.68, 95% CI 1.16 to 2.43; p ¼ 0.006) did not influence this independent relation. The 10-year overall survival in patients with permanent AF and in those with paroxysmal AF was significantly lower compared with patients in SR (both p <0.0001) (Figure 2). However, in patients with AF, postoperative overall survival in patients with permanent AF compared with those with paroxysmal AF tended to be lower (p ¼ 0.091). The combined end point of overall mortality and postoperative heart failure resulted in better 10-year event-free survival in patients in SR than in those with AF (Figure 3). On multivariate analysis, AF (HR 1.61, 95% CI 1.15 to 2.26; p ¼ 0.005) was identified as an independent predictor of combined postoperative overall mortality and heart failure. Further adjustment for LVEF (HR 1.68, 95% CI 1.20 to 2.36; p ¼ 0.003), LV end-systolic diameter (HR 1.68, 95% CI 1.18 to 2.40; p ¼ 0.004), or coronary artery bypass (HR 1.62, 95% CI 1.16 to 2.28; p ¼ 0.005) did not influence this independent relation. The 10-year event-free survival (overall mortality and postoperative heart failure) in patients with permanent AF and in patients with paroxysmal AF was significantly lower compared with those in
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SR (both p <0.0001) (Figure 3). Among patients with AF, 10-year postoperative event-free survival was lower in patients with permanent AF compared with patients with paroxysmal AF (p ¼ 0.022). Among asymptomatic patients (n ¼ 51), there were 35 patients in SR and 16 patients in AF. There were no deaths at follow-up in patients in SR, whereas 5 asymptomatic patients died during follow-up in the AF group. Postoperative overall survival was significantly better in asymptomatic patients in SR compared with those with AF (10-year overall survival of 100% vs 77 12%; p ¼ 0.002). The combined end point of overall mortality and postoperative heart failure resulted in better 10-year event-free survival in asymptomatic patients in SR than in those with AF (100% vs 71 12%; p <0.0001). Patients with preoperative AF compared with those in SR had higher rates of postoperative LVD (23.3% [n ¼ 42] vs 13.4% [n ¼ 33]; p ¼ 0.007; Figure 4). Univariate analysis identified preoperative AF as a predictor of postoperative LVD (odds ratio [OR] 1.87, 95% CI 1.13 to 3.09; p ¼ 0.015). After adjustment by EF, preoperative AF (OR 1.79, 95% CI 1.06 to 3.02; p ¼ 0.03) remained associated with postoperative LVD. Discussion The present study shows that, in patients with organic MR due to MVP and who underwent MVRp, preoperative AF is (1) common (42% of cases), (2) a powerful predictor of long-term postoperative overall mortality and combined postoperative overall mortality and heart failure, and (3) a predictor of postoperative LVD. Furthermore, although patients with paroxysmal AF had a better outcome compared with those with permanent AF, these paroxysmal patients with AF had lower survival than those in SR. Previous studies have reported discordant results concerning the impact of preoperative AF after MVRp on outcome. A retrospective single-center study4 including 323 patients reported no significant difference in terms of 5-year survival between patients with AF and those in SR. However, this study included patients with various causes of primary MR and concomitant aortic valve operation and many patients with coronary artery disease, which may at least partially explain the different results compared with those of our study. Jessurun et al7 in a series, which included not only patients with MVP but also patients with endocarditis, and even mitral stenosis and rheumatic valve disease, reported no significant survival difference between patients with preoperative SR and paroxysmal or permanent AF. However, the investigators showed that the persistence of AF after surgery appeared to be associated with lower survival. Lim et al15 in a series, including a high proportion of patient with rheumatic MR in the AF group, reported that AF affected survival only in univariate analysis but not in multivariate analysis with no distinction between paroxysmal and permanent AF. In line with our results, Eguchi et al6 showed that patients with preoperative AF had a poorer outcome after MVRp, suggesting that mitral surgery should preferably be performed before onset of AF. These data are consistent with those of the Mayo Clinic study showing that onset of AF during conservative
management of patients with AF was associated with increased mortality and morbidity.8 Our results also demonstrated that the outcome of patients with AF is worse than in patients with SR. Furthermore, our results showed a difference in outcome according to the type of AF (i.e., chronic vs paroxysmal) with an excess of overall mortality or heart failure in patients with permanent AF compared with patients with paroxysmal AF. However, despite the excess of overall mortality or heart failure in patients with paroxysmal AF compared with those with SR, patients with paroxysmal AF had better outcome compared with those with permanent AF. Importantly, we showed that preoperative AF was also a predictor of postoperative LVD. Moreover, preoperative pulmonary hypertension and AF in patients who underwent MVRp increased by almost twofold the risk of postoperative LV dysfunction.3 Therefore, waiting for the onset of AF results in excessive postoperative mortality and morbidity (i.e., heart failure and LVD), and the onset of AF must be considered as a decisive turning point in the course of MR because of MVP. In patients presenting for mitral valve surgery with chronic AF, according to guidelines, treatment by a maze procedure should be considered, but the increased morbidity related to this procedure should also be considered. In our series, the 3 patients treated by a maze procedure or other surgical treatments of AF during mitral surgery were excluded to avoid introducing any factor that could influence the postoperative onset of AF. Decision making in the treatment of patients with AF and organic severe MR is complex. When performed at the appropriate time, surgical correction of chronic organic MR should theoretically restore normal LV function16 and geometry and life expectancy. AF is a frequent complication in these patients3e6,17 observed with a frequency of 42% in our population. The presence of AF is currently a class IIa indication for surgery in patients with no distinction between permanent and paroxysmal AF.1,2 Although both American and European guidelines emphasize that new onset of AF constitutes a strong argument for surgery in asymptomatic patients with MR (classes IIaB and IIaC respectively), few data and no obvious proof are available in the literature, and therefore, the level of evidence of these recommendations remains B and C. Accordingly, we reported an excess of mortality, heart failure, and postoperative LVD when patients are operated after onset of AF (even if AF is only paroxysmal). As AF is associated with a worse postoperative outcome, our data strongly suggest that, in the presence of severe MR because of MVP, the first sign of AF (i.e., chronic or paroxysmal) must be considered to be an indication of prompt surgery. The present study was a retrospective analysis of patients’ records and, therefore, has the inherent limitations of such analyses. If these data are confirmed by further prospective studies, they may lead to revision of the current class IIa recommendation2 toward a class I recommendation regarding patients with paroxysmal or permanent AF and severe MR due to MVP with a high probability of durable MVRp. Ideally, MVRp should be considered while patients are still in SR, before onset of AF. Actually, the main determinant of onset of AF in patients with primary MR is LA
Valvular Heart Disease/Atrial Fibrillation Impact on Mitral Regurgitation
dilation. LA diameter or LA volume is helpful for risk stratification of these patients, even when they are asymptomatic.18,19 Therefore, serial measurements of LA dimensions during follow-up may be useful for decision making in patients in SR and to determine optimal timing of surgery for these patients. Thus, in the absence of documented AF, surgery could be discussed in asymptomatic patients with severe organic MR due to MVP with a high probability of MVRp and very low operative risk but presenting obvious LA dilation (indexed LA volume >60 ml/ m2)19 as suggested by the ESC recommendations (class IIbC recommendation).2
9. 10.
Disclosures The authors have no conflicts of interest to disclose. 1. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP III, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM III, Thomas JD; Members AATF. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 2014;129:e521ee643. 2. Joint Task Force on the Management of Valvular Heart Disease of the European Society of C; European Association for Cardio-Thoracic S, Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schafers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33: 2451e2496. 3. Varghese R, Itagaki S, Anyanwu AC, Milla F, Adams DH. Predicting early left ventricular dysfunction after mitral valve reconstruction: the effect of atrial fibrillation and pulmonary hypertension. J Thorac Cardiovasc Surg 2014;148:422e427. 4. Chua YL, Schaff HV, Orszulak TA, Morris JJ. Outcome of mitral valve repair in patients with preoperative atrial fibrillation. Should the maze procedure be combined with mitral valvuloplasty? J Thorac Cardiovasc Surg 1994;107:408e415. 5. Bando K, Kasegawa H, Okada Y, Kobayashi J, Kada A, Shimokawa T, Nasu M, Nakatani S, Niwaya K, Tagusari O, Nakajima H, Hirata M, Yagihara T, Kitamura S. Impact of preoperative and postoperative atrial fibrillation on outcome after mitral valvuloplasty for nonischemic mitral regurgitation. J Thorac Cardiovasc Surg 2005;129:1032e1040. 6. Eguchi K, Ohtaki E, Matsumura T, Tanaka K, Tohbaru T, Iguchi N, Misu K, Asano R, Nagayama M, Sumiyoshi T, Kasegawa H, Hosoda S. Pre-operative atrial fibrillation as the key determinant of outcome of mitral valve repair for degenerative mitral regurgitation. Eur Heart J 2005;26:1866e1872. 7. Jessurun ER, van Hemel NM, Kelder JC, Elbers S, de la Riviere AB, Defauw JJ, Ernst JM. Mitral valve surgery and atrial fibrillation: is atrial fibrillation surgery also needed? Eur J Cardiothorac Surg 2000;17:530e537. 8. Grigioni F, Avierinos JF, Ling LH, Scott CG, Bailey KR, Tajik AJ, Frye RL, Enriquez-Sarano M. Atrial fibrillation complicating the course
11.
12.
13.
14.
15. 16.
17. 18.
19.
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of degenerative mitral regurgitation: determinants and long-term outcome. J Am Coll Cardiol 2002;40:84e92. European System for Cardiac Operation Risk Evaluation. Available at: http://www.Euroscore.Org. 2011. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG; American College of Cardiology; American Heart Association; European Society of Cardiology; North American Society of Pacing, Electrophysiology. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European Society of Cardiology Committee for practice guidelines and policy conferences (committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 2001;22: 1852e1923. Levine RA, Stathogiannis E, Newell JB, Harrigan P, Weyman AE. Reconsideration of echocardiographic standards for mitral valve prolapse: lack of association between leaflet displacement isolated to the apical four chamber view and independent echocardiographic evidence of abnormality. J Am Coll Cardiol 1988;11:1010e1019. Quinones MA, Waggoner AD, Reduto LA, Nelson JG, Young JB, Winters WL Jr, Ribeiro LG, Miller RR. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography. Circulation 1981;64:744e753. Tribouilloy C, Grigioni F, Avierinos JF, Barbieri A, Rusinaru D, Szymanski C, Ferlito M, Tafanelli L, Bursi F, Trojette F, Branzi A, Habib G, Modena MG, Enriquez-Sarano M; Investigators M. Survival implication of left ventricular end-systolic diameter in mitral regurgitation due to flail leaflets a long-term follow-up multicenter study. J Am Coll Cardiol 2009;54:1961e1968. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in m-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58: 1072e1083. Lim E, Barlow CW, Hosseinpour AR, Wisbey C, Wilson K, Pidgeon W, Charman S, Barlow JB, Wells FC. Influence of atrial fibrillation on outcome following mitral valve repair. Circulation 2001;104:I59eI63. Tribouilloy C, Rusinaru D, Szymanski C, Mezghani S, Fournier A, Levy F, Peltier M, Ben Ammar A, Carmi D, Remadi JP, Caus T, Touati G. Predicting left ventricular dysfunction after valve repair for mitral regurgitation due to leaflet prolapse: additive value of left ventricular end-systolic dimension to ejection fraction. Eur J Echocardiogr 2011;12:702e710. Obadia JF, el Farra M, Bastien OH, Lievre M, Martelloni Y, Chassignolle JF. Outcome of atrial fibrillation after mitral valve repair. J Thorac Cardiovasc Surg 1997;114:179e185. Rusinaru D, Tribouilloy C, Grigioni F, Avierinos JF, Suri RM, Barbieri A, Szymanski C, Ferlito M, Michelena H, Tafanelli L, Bursi F, Mezghani S, Branzi A, Habib G, Modena MG, Enriquez-Sarano M; Mitral Regurgitation International DI. Left atrial size is a potent predictor of mortality in mitral regurgitation due to flail leaflets: results from a large international multicenter study. Circ Cardiovasc Imaging 2011;4:473e481. Le Tourneau T, Messika-Zeitoun D, Russo A, Detaint D, Topilsky Y, Mahoney DW, Suri R, Enriquez-Sarano M. Impact of left atrial volume on clinical outcome in organic mitral regurgitation. J Am Coll Cardiol 2010;56:570e578.