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Long-term results of mitral valve repair for severe mitral regurgitation in asymptomatic patients

Open ArchivePublished:May 31, 2018DOI:https://doi.org/10.1016/j.jjcc.2018.04.016

      Highlights

      • Mitral valve surgery for severe degenerative regurgitation in asymptomatic patients is safe.
      • Valve repair is feasible regardless of the complexity of lesions causing valve regurgitation.
      • Early surgery results in life expectancy and quality of life comparable to the general population.
      • Postoperative supraventricular rhythm disturbances are common and need further investigation.

      Abstract

      Background

      In asymptomatic patients with severe degenerative mitral valve regurgitation (MR), early surgery is often performed in experienced centers. The patient- and valve-related results and the quality of life after surgery in these patients remain insufficiently explored.

      Methods

      Between 1/2000 and 12/2015, 83 asymptomatic patients (mean age 56.6 ± 12.6 years, 21 female) without any complications related to long-lasting MR underwent early surgery. Follow-up clinical and echocardiographic data and health-related quality of life assessment (SF-36) were studied and matched to the general population.

      Results

      Repair rate was 100% and early mortality was 0%. Residual MR (≥grade 2+) was seen in 1 (1%) patient who underwent a successful re-repair while 4 (5%) patients needed permanent pacemaker implantation. At a median follow-up of 7.6 (IQR 4.1–11.9) years, 6 late deaths occurred. The 10-year overall survival rate was 91.5% (95% CI 84.2–98.8%) and was comparable to the general population. The health-related quality of life (84% complete) did not differ from the general population. One patient underwent late reintervention. Median echocardiography follow-up was 5.2 years (IQR 2.4–10.4; 98% complete). The 10-year freedom from recurrent MR rate (≥grade 2+) was 86.7% (95% CI 76.1–97.3%). The 10-year freedom from any atrial tachycardia rate was 68.7% (95% CI 55.2–82.2%) while 7 (8%) patients underwent late pacemaker implantation.

      Conclusions

      Early surgical intervention in asymptomatic patients with severe MR can be performed safely and restores normal life expectancy and quality of life. However, the frequency of late arrhythmias and pacemaker implantation is high and needs further evaluation.

      Keywords

      Introduction

      Surgical mitral valve (MV) repair is the treatment of choice for severe mitral regurgitation (MR) due to degenerative disease [
      • Baumgartner H.
      • Falk V.
      • Bax J.J.
      • De Bonis M.
      • Hamm C.
      • Holm P.J.
      • et al.
      2017 ESC/EACTS guidelines for the management of valvular heart disease: the Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
      ,
      • Nishimura R.A.
      • Otto C.M.
      • Bonow R.O.
      • Carabello B.A.
      • Erwin 3rd, J.P.
      • Fleisher L.A.
      • et al.
      2017 AHA/ACC focused update of the 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 Clinical Practice Guidelines.
      ]. The timing of surgery in asymptomatic patients without echocardiographic evidence of left ventricular (LV) functional decline or dilatation remains a matter of debate. Previously, Rosenhek et al. have advised a watchful waiting approach with close clinical and echocardiographic follow-up [
      • Rosenhek R.
      • Rader F.
      • Klaar U.
      • Gabriel H.
      • Krejc M.
      • Kalbeck D.
      • et al.
      Outcome of watchful waiting in asymptomatic severe mitral regurgitation.
      ]. They have shown that even in the presence of severe MR, survival free of an indication for surgery at 8 years can be as high as 55 ± 6%. However, others have shown that severe MR follows a more progressive and malignant course and have recommended an early surgery approach to decrease the early and late valve-related morbidity and mortality rates [
      • Gillinov A.M.
      • Mihaljevic T.
      • Blackstone E.H.
      • George K.
      • Svensson L.G.
      • Nowicki E.R.
      • et al.
      Should patients with severe degenerative mitral regurgitation delay surgery until symptoms develop?.
      ,
      • Goldstone A.B.
      • Patrick W.L.
      • Cohen J.E.
      • Aribeana C.N.
      • Popat R.
      • Woo Y.J.
      Early surgical intervention or watchful waiting for the management of asymptomatic mitral regurgitation: a systematic review and meta-analysis.
      ,
      • Yazdchi F.
      • Koch C.G.
      • Mihaljevic T.
      • Hachamovitch R.
      • Lowry A.M.
      • He J.
      • et al.
      Increasing disadvantage of “watchful waiting” for repairing degenerative mitral valve disease.
      ,
      • David T.E.
      • Armstrong S.
      • McCrindle B.W.
      • Manlhiot C.
      Late outcomes of mitral valve repair for mitral regurgitation due to degenerative disease.
      ,
      • Suri R.M.
      • Aviernos J.F.
      • Dearani J.A.
      • Mahoney D.W.
      • Michelena H.I.
      • Schaff H.V.
      • et al.
      Management of less-than-severe mitral regurgitation: should guidelines recommend earlier surgical intervention?.
      ,
      • Ling L.H.
      • Enriquez-Sarano M.
      • Seward J.B.
      • Tajik A.J.
      • Schaff H.V.
      • Bailey K.R.
      • et al.
      Clinical outcome of mitral regurgitation due to flail leaflet.
      ].
      Current guidelines recommend early surgery only when the risk of surgery is low and expected probability of a durable valve repair is high [
      • Baumgartner H.
      • Falk V.
      • Bax J.J.
      • De Bonis M.
      • Hamm C.
      • Holm P.J.
      • et al.
      2017 ESC/EACTS guidelines for the management of valvular heart disease: the Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
      ,
      • Nishimura R.A.
      • Otto C.M.
      • Bonow R.O.
      • Carabello B.A.
      • Erwin 3rd, J.P.
      • Fleisher L.A.
      • et al.
      2017 AHA/ACC focused update of the 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 Clinical Practice Guidelines.
      ]. In centers experienced in reconstructive MV surgery, the results of valve repair for degenerative disease have progressively improved and a durable repair will nowadays be possible in almost all of these patients, regardless of repair complexity [
      • Castillo J.G.
      • Anyanwu A.C.
      • Fuster V.
      • Adams D.H.
      A near 100% repair rate for mitral valve prolapse is achievable in a reference center: implications for future guidelines.
      ,
      • Goldstone A.B.
      • Cohen J.E.
      • Howard J.L.
      • Edwards B.B.
      • Acker A.L.
      • Hiesinger W.
      • et al.
      A “repair-all” strategy for degenerative mitral valve disease safely minimizes unnecessary replacement.
      ,
      • Perier P.
      • Hohenberger W.
      • Lakew F.
      • Batz G.
      • Diegeler A.
      Rate of repair in minimally invasive mitral valve surgery.
      ]. This has encouraged a more aggressive early surgery approach and a growing number of patients undergo surgery prior to the development of symptoms or before meeting other criteria for surgical intervention. However, patients are potentially exposed to perioperative morbidity and mortality, unanticipated valve replacement with proven negative influence on long-term survival [
      • Lazam S.
      • Vanoverschelde J.L.
      • Tribouilloy C.
      • Grigioni F.
      • Suri R.M.
      • Avierinos J.F.
      • et al.
      Twenty-year outcome after mitral repair versus replacement for severe degenerative mitral regurgitation: analysis of a large, prospective, multicenter, international registry.
      ], and the possibility of valve repair failure. The early and late outcomes of valve repair in completely asymptomatic patients with severe MR due to degenerative valve disease remain insufficiently explored.
      The aim of this study was to explore the patient- and valve-related results of surgical intervention for severe MR in truly asymptomatic patients with degenerative valve disease. We aim to explore the clinical and echocardiographic outcomes of these patients and to compare the overall survival and quality of life to the age- and gender-matched general population.

      Methods

      Patients

      Between January 2000 and December 2015, 684 consecutive patients underwent surgical intervention for degenerative MV disease at our institution. For the purpose of this study we included only elective asymptomatic patients [New York Heart Association (NYHA) class I] without any clinical or echocardiographic complications related to long-lasting MR. The latter included LV dilatation (LV end systolic diameter ≥45 mm), reduced LV ejection fraction (≤60%), pulmonary hypertension (resting systolic pulmonary artery pressure >50 mmHg or ≥60 mmHg during exercise) or history of atrial fibrillation (AF). Patients with symptomatic coronary artery disease were excluded as this would have affected the timing of surgery. On the other hand, patients with asymptomatic coronary artery disease in whom coronary artery bypass grafting was performed due to an abnormal preoperative coronary angiogram were not excluded.
      Only patients referred for surgery due to an asymptomatic heart murmur detected unexpectedly during physical examination for reasons of life-insurance acceptance or work-related check-up that warranted further investigation were included. During the study period, we recommended surgery to all asymptomatic patients with severe MR referred to our institution. All valves were deemed repairable, regardless of the expected repair complexity.

      Follow-up

      Preoperative, intraoperative, and postoperative data were prospectively collected in our computerized database and retrospectively analyzed. Follow-up survival, clinical, and echocardiographic data were collected through clinical visits at our institution or affiliated hospitals, and through questionnaires obtained from patients. Approximately one-half of all follow-up echocardiographic studies were performed at our institution and the other half in affiliated hospitals. Whenever the report from an outside laboratory indicated ≥grade 2+ MR, the study was reviewed in our hospital. The study was approved by our Institutional Ethics Committee and written informed consent was obtained.

      Study endpoints

      Early mortality was defined as mortality within 30-days after the operation or during the index hospitalization. Postoperative mortality and morbidity endpoints were defined according to the joint Society of Thoracic Surgeons, American Association for Thoracic Surgery, and European Association for Cardio-Thoracic Surgery Guidelines [
      • Akins C.W.
      • Miller D.C.
      • Turina M.I.
      • Kouchoukos N.T.
      • Blackstone E.H.
      • Grunkemeier G.L.
      • et al.
      Guidelines for reporting mortality and morbidity after cardiac valve interventions.
      ]. Additional endpoints included freedom from any atrial tachycardia (AT; further divided in freedom from AF, and other AT), hospitalization for heart failure, and pacemaker implantation. Severity of MR was quantitatively assessed according to current recommendations using a multi-parametric approach and including the effective regurgitant orifice area (using proximal isovelocity surface area method) and regurgitant volume measurements [
      • Baumgartner H.
      • Falk V.
      • Bax J.J.
      • De Bonis M.
      • Hamm C.
      • Holm P.J.
      • et al.
      2017 ESC/EACTS guidelines for the management of valvular heart disease.
      ]. MR severity was graded as: 0 (none), 1+ (mild), 2+ (moderate), 3+ (moderate-to-severe), and 4+ (severe). Residual and recurrent MR were defined as ≥grade 2+ MR.

      Quality of life assessment

      The health-related quality of life assessment was conducted using the SF-36 quality of life questionnaire. It contains questions clustered in 8 domains: physical functioning, physical role functioning, bodily pain, general health perceptions, vitality, social functioning, emotional role functioning, and general mental health. Raw scores are calculated as the sum of (re-coded) scale items and transformed to a 0–100 scale. The domains are then summarized to form 2 summary measures, the Physical Component Score and Mental Component Score. The scales are obtained by summing the domains together within a component. Thereafter, the scores are divided by the range of scores and transformed into a scale. The mean score of both components is 50 with a standard deviation (SD) of 10. Higher scores represent better health status. The study by Aaronson et al. was used to compare the health-related quality of life between the general Dutch population and the study population [
      • Aaronson N.K.
      • Muller M.
      • Cohen P.D.
      • Essink-Bot M.L.
      • Fekkes M.
      • Sanderman R.
      • et al.
      Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations.
      ].

      Surgical technique

      Surgery was performed through median sternotomy (n = 68), lateral mini thoracotomy (n = 11), or hemi-sternotomy (n = 4). Antegrade and/or retrograde warm blood cardioplegia was used for cardioprotection in all cases. When longer cardiopulmonary bypass times were anticipated, mild systemic hypothermia was applied. Blood cardioplegia was administered in intervals of 15 or 20 (in case of hypothermia) minutes. In the vast majority of patients (n = 77), the MV was exposed transseptally.
      Repair techniques used included chordal replacement for anterior MV leaflet prolapse. Commissural prolapse was treated predominantly by papillary muscle head repositioning. For the posterior MV leaflet, a combination of resection and neochords techniques, aimed at resolving leaflet prolapse and excessive tissue in height and/or width, were used. Earlier in the study period, annular plication was performed in selected patients. Intraoperative echocardiography was performed by an experienced cardiologist to analyze the result of valve repair.
      Prior to 2004, tricuspid valve (TV) repair was performed only when ≥moderate tricuspid regurgitation was present on preoperative echocardiography. Since 2004, this was performed also in the presence of significant tricuspid annulus dilatation (≥40 mm or ≥21 mm/m2 body surface area), regardless of the amount of regurgitation.
      Pre-discharge echocardiography was performed in all patients. Oral anticoagulation was initiated for the first 3 months after surgery with a target international normalized ratio of 2.0–3.0. In the absence of other indications, oral anticoagulation was discontinued thereafter.

      Statistical analysis

      Continuous data are presented as means ± standard deviation for normally distributed data or medians and interquartile ranges (IQR) when not normally distributed. Categorical data are presented as counts and percentages. Survival and freedom from time-related events were estimated using the Kaplan–Meier method. Age- and gender-matched survival in the general population were calculated using the Dutch population life tables (http://statline.cbs.nl/). Statistical analysis was performed using the IBM Statistics for Windows, version 23.0 (SPSS, Inc., IBM Corporation, Armonk, NY, USA).

      Results

      Baseline characteristics and surgical procedure

      The median patient age was 56.6 ± 12.6 years and the majority of patients were male (Table 1). Overall, the proportion of patients with any significant comorbidities and the estimated risk of surgical mortality were low. Mitral valve repair rate was 100%. The details on surgical techniques used are shown in Table 2. Intraoperative echocardiography demonstrated no significant residual MR in all cases.
      Table 1Baseline characteristics.
      N = 83
      Age (years)56.6 ± 12.6
      Gender (female)21 (25)
      Hypertension31 (37)
      Renal impairment
       Moderate (CC 85–50 ml/min)26 (31)
       Severe (CC <50 ml/min)1 (1)
      History of TIA or CVA2 (2)
      Chronic lung disease3 (4)
      Diabetes mellitus1 (1)
      Echocardiographic characteristics
       Left ventricular ejection fraction (%)69 ± 5
       Left ventricular end diastolic diameter (mm)54 ± 6
       Left ventricular end systolic diameter (mm)32 ± 5
       Systolic pulmonary artery pressure (mmHg)28 ± 7
      Site of leaflet prolapse
       Isolated posterior50 (60)
        Flail leaflet21 (25)
       Bileaflet25 (30)
        Flail leaflet5 (6)
       Isolated anterior7 (9)
        Flail leaflet6 (7)
       None1 (1)
      Annular calcification7 (8)
      EuroSCORE II0.86 (IQR 0.59–1.08)
      Data are presented as N (%) and means ± standard deviation or medians (IQR). Abbreviations: CC: creatinine clearance; CVA: cerebrovascular accident; TIA: transient ischemic attack.
      Table 2Intraoperative details.
      N = 83
      Mitral valve annulus
       Plication25 (30)
       Decalcification6 (7)
       Annuloplasty83 (100)
      Anterior mitral valve leaflet
       PTFE neochords27 (33)
      Posterior mitral valve leaflet
       Resection
        Triangular17 (20)
        Quadrangular47 (37)
       Sliding plasty44 (53)
       PTFE neochords31 (37)
       Chordal transfer1 (1)
       Papillary muscle head repositioning1 (1)
       Indentation closure13 (16)
      Commissures
       Anterior commissure
        Papillary muscle head repositioning2 (2)
        Commissuroplasty2 (2)
       Posterior commissure
        Papillary muscle head repositioning14 (17)
        Papillary muscle shortening1 (1)
        Commissuroplasty7 (8)
        PTFE neochords1 (1)
      Concomitant procedures
       Tricuspid valve repair28 (34)
       Coronary artery bypass grafting6 (7)
      Second pump run4 (5)
      Cardiopulmonary bypass time (min)176 (IQR 145–202)
      Aortic cross-clamp time (min)139 (IQR 115–158)
      Data are presented as N (%) and medians (IQR). Abbreviations: IQR: interquartile range; PTFE: polytetrafluoroethylene.

      Early outcomes

      There was no early mortality. No major complications occurred in the majority of patients (Table 3). In 1 (1%) patient, pre-discharge echocardiography demonstrated residual, grade 3+ MR due to residual posterior MV leaflet prolapse. The patient underwent a MV re-repair on postoperative day 10 and the further postoperative course was uneventful. Furthermore, postoperative permanent pacemaker implantation was needed in 4 (5%) patients (due to complete heart block in 3 and atrial flutter with symptomatic bradycardia in 1). Postoperative pacemaker implantation was more commonly performed in patients with concomitant TV repair (3/28 versus 1/55), albeit the difference was statistically not significant (p = 0.074). The incidence of pacemaker implantation in patients undergoing prophylactic TV repair was highest soon after the indication for TV repair was extended to isolated annular dilatation in 2004 and 2005 (2/3 cases of pacemaker implantations in this group). From 2006 on, pacemaker implantation was needed in 1/19 patients in whom concomitant TV repair was performed.
      Table 3Postoperative complications.
      N = 83
      Early mortality0 (0)
      Deep sternal wound infection0 (0)
      Prolonged intubation (>24 h)1
      Renal failure0 (0)
      Permanent stroke0 (0)
      Early reoperation6 (7)
       Early valve reoperation1 (1)
       Re-sternotomy for other causes0 (0)
       Subxyphoidal pericardiotomy5 (6)
      ICU stay (days)1 (IQR 1–2)
      Permanent pacemaker implantation4 (5)
      Postoperative supraventricular tachycardia37 (45)
      Data are presented as N (%) and medians (IQR). Abbreviations: ICU: intensive care unit; IQR interquartile range.

      Late mortality

      Median survival follow-up was 7.3 years (IQR 3.7–11.9; 654 total follow-up years) and was 99% complete (1 patient was lost to follow-up due to emigration). Six late deaths occurred and the cause of death was cardiac-related in 3 patients; all of these were sudden, unexplained deaths. The most recent follow-up echocardiography revealed no significant MR and good LV function in 2 and no significant MR and mildly impaired LV function without any significant MR in 1 of these patients. The 5- and 10-year overall survival rates were 95.4% (95% CI 90.3–100%) and 91.5% (95% CI 84.2–98.8%), respectively. Overall survival was comparable to the age- and gender-matched general population (Fig. 1).
      Figure thumbnail gr1
      Fig. 1Overall survival of patients with asymptomatic severe mitral valve regurgitation (solid line) compared to the age- and gender-matched general population (dashed line).

      Late morbidity

      Clinical follow-up was 93% complete [median follow-up duration 7.0 (IQR 3.2–11.2) years]. Valve-related morbidity included 6 thromboembolic events (1 cerebrovascular accident and 5 transient ischemic attacks); 2 severe bleeding events (1 of these patients was on oral anticoagulation with an international normalized ratio level of 4.5 at the time of the event); and 2 hospitalizations for heart failure. The linearized event rates were 1.0%/patient year for thromboembolic events, 0.34%/patient year for hospitalization for heart failure, and 0.34%/patient year for severe bleeding event.
      De novo ATs occurred often during the follow-up period and the freedom from any AT rates at 5- and 10-years after surgery were 84.8% (95% CI 76.4–93.2%) and 68.7% (95% CI 55.2–82.2%), respectively (Fig. 2). At the time of last follow-up (mean patient age 64.0 ± 12.8 years), the prevalence of AF was 12%. The 10-year freedom from AF rate was 84.1% (95% CI 73.7–94.5%). The 10-year freedom from other ATs rate was 81.0% (95% CI 69.0–92.9%). Following hospital discharge, 7 (8%) patients underwent late pacemaker implantation. The indication for permanent pacemaker implantation was brady-tachy syndrome in 4, total atrioventricular block in 2, and sinoatrial node dysfunction in 1.
      Figure thumbnail gr2
      Fig. 2Freedom from late morbidity: (A) freedom from any atrial tachycardia; (B) freedom from atrial fibrillation; (C) freedom from other types of atrial tachycardia; (D) freedom from pacemaker implantation.
      At the time of last follow-up, 64 (85%) patients were in NYHA class I, 10 (14%) in NYHA class II, and 1 (1%) in NYHA class III. Recurrent MR was present in 2/11 of symptomatic patients, providing an explanation for their status. The remaining causes that could possibly explain the symptomatic status were: impaired LV function (mildly in 3 and moderately in 1) in 4/9, AT in 4/9 and functional MV stenosis (postoperative mean MV pressure gradient ≥5 mmHg) in 3/9 patients.
      During the follow-up period, 1 late MV reintervention was performed. Recurrent MR was first detected 7 years after the initial operation. A few years prior to this observation, the patient underwent pacemaker implantation that resulted in almost exclusive right ventricular pacing and led to LV dyssynchrony, dilatation, and functional decline. Biventricular pacing failed to resolve the issue. Echocardiography demonstrated posterior MV leaflet restriction with pseudo-prolapse of the anterior leaflet at the height of the posterior commissure. A MitraClip (Abbott Vascular, Santa Clara, CA, USA) implantation (9.1 years after the initial operation) was performed. At last echocardiographic follow-up, no significant MR was present.

      Late echocardiographic outcome

      The mean echocardiographic follow-up time was 5.2 (IQR 2.4–10.4) years and was 98% complete. Freedom from recurrent (≥grade 2+) MR rate at 5- and 10-years after surgery was 95.6% (95% CI 90.7–100%) and 86.7% (95% CI 76.1–97.3%), respectively (Fig. 3). At the time of last echocardiographic follow-up, no significant MR (≤grade 1+) was seen in 74 (91%) patients, grade 2+ MR in 5 (6%), and ≥grade 3+ MR in 2 (3%) patients, the latter including the patient who later underwent MitraClip implantation.
      Figure thumbnail gr3
      Fig. 3Freedom from recurrent (freedom from ≥grade 2+ and ≥grade 3+ mitral regurgitation are presented separately; patients at risk for freedom form ≥grade 3+ mitral regurgitation are presented in brackets) mitral regurgitation (MR) (above) and late mitral valve reintervention (below).

      Quality of life

      A total of 65 patients (84% complete for patients alive at follow-up, mean follow-up time 7.2 ± 4.3 years) completed the SF-36 quality of life questionnaire. One questionnaire had to be discarded due to insufficient data. The mean patient age at the time of follow-up was 64.3 ± 12.1 years and 16/64 (25%) patients were female. Compared to the general age- and sex-matched population, the study population performed better in several individual domains of the SF-36 quality of life assessment (Table 4). The Physical and Mental Component Scores were comparable to the matched population.
      Table 4The results of the SF-36 quality of life questionnaire compared to the age- and gender-matched general population derived from the study of Aaronson et al.
      • Aaronson N.K.
      • Muller M.
      • Cohen P.D.
      • Essink-Bot M.L.
      • Fekkes M.
      • Sanderman R.
      • et al.
      Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations.
      .
      Study population (n = 64)Matched general populationP-value
      MeanSDMeanSD
      PF83.122.277.122.60.001
      RP75.839.670.839.10.13
      BP84.923.270.924.2<0.001
      GH65.523.365.019.70.72
      VT69.417.569.218.90.62
      SF87.518.982.822.50.014
      RE87.528.282.632.3<0.001
      MH82.313.275.717.8<0.001
      PCS49.510.346.810.2/
      MCS52.16.850.89.8/
      Abbreviations: PF: physical functioning; RP: role-physical; BP: bodily pain; GH: general health; VT: vitality; SD: standard deviation; SF: social functioning; RE: role-emotional; MH: mental health; PCS: physical component score; MCS: mental component score.

      Discussion

      Our results demonstrate that early surgery in asymptomatic patients with severe MR, prior to the occurrence of complications related to long-standing MR, is safe and valve repair is feasible in all cases, regardless of repair complexity. After successful repair, the life expectancy and quality of life are comparable to the general population, making early intervention justified.
      Surgical MV repair is the gold standard for treatment of severe MR due to degenerative MV disease. The documented high repair rates and good repair durability have motivated surgeons to advise early surgery in asymptomatic patients prior to the occurrence of complications related to long-standing severe MR [
      • Gillinov A.M.
      • Mihaljevic T.
      • Blackstone E.H.
      • George K.
      • Svensson L.G.
      • Nowicki E.R.
      • et al.
      Should patients with severe degenerative mitral regurgitation delay surgery until symptoms develop?.
      ,
      • Goldstone A.B.
      • Patrick W.L.
      • Cohen J.E.
      • Aribeana C.N.
      • Popat R.
      • Woo Y.J.
      Early surgical intervention or watchful waiting for the management of asymptomatic mitral regurgitation: a systematic review and meta-analysis.
      ,
      • Yazdchi F.
      • Koch C.G.
      • Mihaljevic T.
      • Hachamovitch R.
      • Lowry A.M.
      • He J.
      • et al.
      Increasing disadvantage of “watchful waiting” for repairing degenerative mitral valve disease.
      ,
      • van Leeuwen W.J.
      • Head S.J.
      • de Groot-de Laat L.E.
      • Geleijnse M.L.
      • Bogers A.J.
      • Van Herwerden L.A.
      • et al.
      Single-centre experience with mitral valve repair in asymptomatic patients with severe mitral valve regurgitation.
      ]. The recently updated European Society of Cardiology/European Association of Cardio-Thoracic Surgery guidelines for the management of valvular heart disease remain, however, conservative when it comes to early surgery for severe asymptomatic degenerative MR [
      • Baumgartner H.
      • Falk V.
      • Bax J.J.
      • De Bonis M.
      • Hamm C.
      • Holm P.J.
      • et al.
      2017 ESC/EACTS guidelines for the management of valvular heart disease: the Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
      ]. Clearly, early surgery should be performed exclusively when the expected risk of surgery is low and the probability of valve repair (without residual MR) is high. According to the guidelines, however, surgery in asymptomatic patients without clinical or echocardiographic complications of long-standing MR should only be considered when favorable anatomy (flail leaflet) is present [
      • Baumgartner H.
      • Falk V.
      • Bax J.J.
      • De Bonis M.
      • Hamm C.
      • Holm P.J.
      • et al.
      2017 ESC/EACTS guidelines for the management of valvular heart disease: the Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
      ]. On the other hand, the recently updated American Heart Association/American College of Cardiology valvular heart disease guidelines advise considering surgery irrespective of the projected valve repair complexity [
      • Nishimura R.A.
      • Otto C.M.
      • Bonow R.O.
      • Carabello B.A.
      • Erwin 3rd, J.P.
      • Fleisher L.A.
      • et al.
      2017 AHA/ACC focused update of the 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 Clinical Practice Guidelines.
      ]. Importantly, the North American guidelines recognize progressive increase in LV size or decrease in LV function on serial echocardiographic studies as early markers of disease progression. This is in line with recent evidence that postoperative (irreversible) LV functional decline will occur often even in patients with “preserved” LV function (ejection fraction >60%) [
      • Quintana E.
      • Suri R.M.
      • Thalji N.M.
      • Daly R.C.
      • Dearani J.A.
      • Burkhart H.M.
      • et al.
      Left ventricular dysfunction after mitral valve repair – the fallacy of “normal” preoperative myocardial function.
      ] and is to be attributed to chronic oxidative stress that causes disruption of the cardiomyocyte cytoskeletal-mitochondrial architecture in these patients [
      • Ahmed M.I.
      • Guichard J.L.
      • Rajasekaran N.S.
      • Ahmad S.
      • Mariappan N.
      • Litovsky S.
      • et al.
      Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function.
      ].
      The rationale behind early surgical intervention is that restoring MV competence will prevent otherwise inevitable morphological and functional changes of the LV and left atrium and the consequences thereof. However, the risks of open-heart surgery are not negligible and the potentially detrimental effects of unexpected valve replacement need to be taken into account. A recent report from the Mitral regurgitation International DAtabase (MIDA) registry clearly demonstrated long-term superiority of valve repair over replacement in terms of survival and freedom from valve-related complications [
      • Lazam S.
      • Vanoverschelde J.L.
      • Tribouilloy C.
      • Grigioni F.
      • Suri R.M.
      • Avierinos J.F.
      • et al.
      Twenty-year outcome after mitral repair versus replacement for severe degenerative mitral regurgitation: analysis of a large, prospective, multicenter, international registry.
      ]. Valve replacement in an asymptomatic patient is probably more detrimental for the long-term patient prognosis than a watchful waiting approach. It has been shown that the probability of valve repair is highly variable and depends on center and surgeon experience [
      • Chikwe J.
      • Toyoda N.
      • Anyanwu A.C.
      • Itagaki S.
      • Egorova N.N.
      • Boateng P.
      • et al.
      Relation of mitral valve surgery volume to repair rate, durability, and survival.
      ]. When an early surgery approach is chosen, patients should be referred to a center with sufficient experience in reconstructive valve surgery and documented good results.
      During the study period, we have applied an early surgery approach in asymptomatic patients, irrespective of projected repair complexity. Typically, these patients are young and vital and the expected perioperative morbidity and mortality will nearly always be low. It should be kept in mind that a prolonged history of asymptomatic MR will most often be observed in patients with complex valve abnormalities [
      • Adams D.H.
      • Rosenhek R.
      • Falk V.
      Degenerative mitral valve regurgitation: best practice revolution.
      ], as also observed in this study. Only 25% of patients had a pathology that could be classified as isolated “flail posterior leaflet”. As nowadays a durable valve repair is feasible in the majority of patients with complex lesions [
      • Castillo J.G.
      • Anyanwu A.C.
      • Fuster V.
      • Adams D.H.
      A near 100% repair rate for mitral valve prolapse is achievable in a reference center: implications for future guidelines.
      ,
      • Tomsic A.
      • Hiemstra Y.L.
      • van der Pas S.L.
      • Putter H.
      • Versteegh M.I.M.
      • van Brakel T.J.
      • et al.
      Early and long-term outcomes of mitral valve repair for Barlow's disease: a single-centre 16-year experience.
      ], we reason that the complexity of valve repair should not result in a delayed referral to surgery. Currently, no randomized clinical trials aimed at resolving the issue of the timing of surgery in severe primary MR are available. The evidence to support the early surgery approach derives from a very limited number of prospective registries and, largely, retrospective studies. Moreover, these often include patients with either favorable pathology (flail leaflet) or define early surgery solely as the absence of Class I indications for surgery, as in the case of a report from the MIDA registry [
      • Suri R.M.
      • Vanoverschelde J.L.
      • Grigioni F.
      • Schaff H.V.
      • Tribouilloy C.
      • Avierinos J.F.
      • et al.
      Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets.
      ]. On the other hand, a multi-center prospective registry reported by Kang et al. included 610 consecutive patients with severe organic MR irrespective of valve morphology who underwent either early surgery (n = 235; repair rate 94%) or conventional treatment (n = 375; watchful waiting) and reported superior results with the early surgery approach [
      • Kang D.H.
      • Park S.J.
      • Sun B.J.
      • Cho E.J.
      • Kim D.H.
      • Yun S.C.
      • et al.
      Early surgery versus conventional treatment for asymptomatic severe mitral regurgitation: a propensity analysis.
      ].
      Early and late permanent pacemaker implantation was needed in 4 and 7 of our patients, respectively. The incidence of early pacemaker implantation was higher in patients with concomitant TV repair, although the absolute number of patients is very low and no definite conclusion can be drawn. In a recent study, Jouan et al. encountered similar observations and highlighted the problem of increased rates of high-grade heart conduction disorders and pacemaker implantations related to concomitant TV repair in patients undergoing MV surgery [
      • Jouan J.
      • Mele A.
      • Florens E.
      • Chatellier G.
      • Carpentier A.
      • Achouh P.
      • et al.
      Conduction disorders after tricuspid annuloplasty with mitral valve surgery: Implications for earlier tricuspid intervention.
      ]. In our experience, the majority of early pacemaker implantations was needed early after the indication for concomitant TV repair was extended to isolated annular dilatation. Hereafter, the incidence of early pacemaker implantation in this group declined and was comparable to previous reports [
      • Jouan J.
      • Mele A.
      • Florens E.
      • Chatellier G.
      • Carpentier A.
      • Achouh P.
      • et al.
      Conduction disorders after tricuspid annuloplasty with mitral valve surgery: Implications for earlier tricuspid intervention.
      ,
      • Dreyfus G.D.
      • Corbi P.J.
      • Chan K.M.
      • Bahrami T.
      Secondary tricuspid regurgitation or dilatation: which should be the criteria for surgical repair?.
      ]. Comparing the incidence of pacemaker implantation between patients with and without an indication for concomitant TV repair is somehow misleading due to more advanced disease progression in patients with TV annular dilatation.
      The most commonly observed late morbidity was ATs. Compared with the data from the Rotterdam study [
      • Heeringa J.
      • van der Kuip D.A.
      • Hofman A.
      • Kors J.A.
      • van Herpen G.
      • Stricker B.H.
      • et al.
      Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study.
      ], the prevalence of AF in our study cohort was 5.7 times higher when compared to age- and gender-matched general Dutch population. As the vast majority of patients demonstrated good valve repair function, recurrent MR does not provide a possible explanation for this finding. Likely, this occurred due to the fact that asymptomatic but hemodynamically significant MR was present for a prolonged period prior to the diagnosis and resulted in irreversible functional changes to the left atrium. In a study of 573 patients in sinus rhythm who underwent surgery for severe MR, Stulak et al. demonstrated that new-onset late AF is common after MV surgery with a cumulative risk of occurrence of 23% at 10 years after surgery [
      • Stulak J.M.
      • Suri R.M.
      • Dearani J.A.
      • Sundt 3rd, T.M.
      • Schaff H.V.
      When should prophylactic maze procedure be considered in patients undergoing mitral valve surgery?.
      ]. Comparable results were also reported by Suri et al. in an analysis of 902 asymptomatic patients with severe MR from the MIDA registry who, interestingly, failed to demonstrate any beneficial effect of early surgery on the occurrence of new AF when compared to watchful waiting [
      • Suri R.M.
      • Vanoverschelde J.L.
      • Grigioni F.
      • Schaff H.V.
      • Tribouilloy C.
      • Avierinos J.F.
      • et al.
      Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets.
      ]. These results are all in line with our observations and bring to question whether prophylactic rhythm intervention should be performed at the time of MV surgery. Better documentation of the likely presence of occult AF prior to surgery might identify patients in whom ablation might readily be indicated.
      In our experience, other types of ATs were also common. The occurrence of such rhythm abnormalities can be explained by surgical trauma and scarring at surgical incision or cannulation sites that provide a substrate for re-entry tachycardias and thus present a direct consequence of surgical intervention [
      • Enriquez A.
      • Santangeli P.
      • Zado E.S.
      • Liang J.
      • Castro S.
      • Garcia F.C.
      • et al.
      Postoperative atrial tachycardias after mitral valve surgery: mechanisms and outcomes of catheter ablation.
      ,
      • Markowitz S.M.
      • Brodman R.F.
      • Stein K.M.
      • Mittal S.
      • Slotwiner D.J.
      • Iwai S.
      • et al.
      Lesional tachycardias related to mitral valve surgery.
      ]. To the best of our knowledge, this topic has been poorly studied to date and the incidence observed in our study is difficult to evaluate critically. Enriquez et al. studied the electrophysiological mechanisms and outcomes of catheter ablation in 67 patients presenting with ATs after previous MV surgery [
      • Enriquez A.
      • Santangeli P.
      • Zado E.S.
      • Liang J.
      • Castro S.
      • Garcia F.C.
      • et al.
      Postoperative atrial tachycardias after mitral valve surgery: mechanisms and outcomes of catheter ablation.
      ]. Interestingly, the left atrium was the chamber of origin more commonly in patients after previous concomitant surgical AF ablation. On the other hand, right-sided ATs were more common in patients with right atriotomy scars. Additionally, a study by Lukac et al. found that the superior transseptal approach created a corridor of slow conduction between the right atriotomy scar and the tricuspid annulus that might predispose to the occurrence of right-sided ATs [
      • Lukac P.
      • Hjortdal V.
      • Pedersen A.K.
      • Jensen H.K.
      • Mortensen P.T.
      • Hansen P.S.
      The superior transseptal surgical approach to mitral valve creates slow conduction.
      ]. Due to the absence of studies designed to assess the freedom from late ATs, the clinical significance of these observations is unknown. In a recent review of literature, Boulemden et al. evaluated the effect of the type of atrial approach to the mitral valve and found no difference on outcomes when left atriotomy was compared to the transseptal approach [
      • Boulemden A.
      • Nadarajah D.
      • Szafranek A.
      • Richens D.
      Atrial approaches to the mitral valve: is there a difference in postoperative rhythm disturbance and permanent pacemaker implantation?.
      ]. Nevertheless, the majority of studies available for inclusion in the review explored only the freedom from early rhythm abnormalities. We standardly use the transseptal approach during MV surgery and this prevented us from comparing the effect of the type of incision used on the incidence of ATs. As ATs significantly affect the quality of life and necessitate oral anticoagulation, more research is needed on how these are to be prevented.

      Limitations

      This is a single-center experience with limitations inherent to the study design. Our study was a single-arm study that did not include a comparable cohort of patients with asymptomatic severe MR in whom no early surgery would be performed. Moreover, no data on preoperative health-related quality of life was available. To overcome these drawbacks, the results were compared to the age- and gender-matched general population. The rhythm follow-up was conducted by the referring cardiologists; systematic follow up with 24-h Holter monitoring might have revealed additional, clinically silent rhythm disturbances.

      Conclusion

      Early surgical intervention for asymptomatic patients with severe MR is safe and a durable valve repair is achievable regardless of repair complexity. Furthermore, following successful early surgery, the life expectancy and quality of life are comparable to the general population. However, even after a successful valve repair, the frequency of ATs and pacemaker implantation is high and warrants further evaluation.

      Conflicts of interest

      None declared.

      Funding

      None.

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