Development of Mitral Stenosis After Mitral Valve Repair: Importance of Mitral Valve Area

Development of Mitral Stenosis After Mitral Valve Repair: Importance of Mitral Valve Area

Accepted Manuscript Development of mitral stenosis after mitral valve repair: Importance of mitral valve area Kwan Leung Chan, MD FRCPC, FAHA, FACC, S...

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Accepted Manuscript Development of mitral stenosis after mitral valve repair: Importance of mitral valve area Kwan Leung Chan, MD FRCPC, FAHA, FACC, Shin-Yee Chen, MD FRCPC, Thierry Mesana, MD FRCSC, Buu Khanh Lam, MD FRCSC PII:

S0828-282X(17)30988-1

DOI:

10.1016/j.cjca.2017.08.027

Reference:

CJCA 2593

To appear in:

Canadian Journal of Cardiology

Received Date: 23 June 2017 Revised Date:

4 August 2017

Accepted Date: 7 August 2017

Please cite this article as: Chan KL, Chen S-Y, Mesana T, Lam BK, Development of mitral stenosis after mitral valve repair: Importance of mitral valve area, Canadian Journal of Cardiology (2017), doi: 10.1016/ j.cjca.2017.08.027. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Development of mitral stenosis after mitral valve repair: Importance of mitral valve area

Word Count: 4737 Kwan Leung Chan, MD FRCPC, FAHA, FACCa

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Email: [email protected]

Shin-Yee Chen, MD FRCPCa,1

Email: [email protected]

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Buu Khanh Lam, MD FRCSCa

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Email: [email protected]

Thierry Mesana, MD FRCSCa

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Short title: Mitral stenosis after mitral repair

Email: [email protected]

Affiliation: Work performed at the University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7 Canada

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Present Address: Pace Cardiology, Little Lake Medical Centre, Unit 302, 11 Lakeside Terrace Barrie ON L4M 0H9 Canada

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Corresponding Author:

Kwan Leung Chan, MD FRCP University of Ottawa Heart Institute 40 Ruskin Street, H3412 Ottawa, ON K1Y 4W7 Tel: 613-761-4189 Fax: 613-761-4170 Email: [email protected]

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Summary Mitral valve repair is preferred to valve replacement in patients with degenerative mitral

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regurgitation. We showed that mitral stenosis defined by mitral valve area ≤ 1.5 cm2 developed in 22 of 110 patients after mitral valve repair and was associated with the use of complete

annular ring. Patients with mitral stenosis had lower exercise capacity, worse perception of well-

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being and adverse outcome events during follow-up.

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Abstract Background

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Development of mitral stenosis (MS) is not uncommon following mitral valve repair for degenerative mitral regurgitation (MR), but the significance of MS in this setting has not been defined.

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Methods

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We prospectively studied 110 such patients who underwent supine bicycle exercise test to assess intracardiac hemodynamics at rest and at peak exercise. B-type natriuretic peptide (BNP) levels were measured at rest and following the exercise test. They also performed 6-minutes walk and completed the short form 36-Item Health Survey Questionnaire. Follow-up was performed by a

Results

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review of the medical record and telephone interview.

Of 110 patients, 22 had MS defined by a mitral valve area (MVA) ≤ 1.5 cm2. The resting and

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peak exercise mitral gradients and pulmonary artery systolic pressure were significantly higher in patients with MS compared to patients with MVA > 1.5 cm2. Resting and post exercise BNP

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levels were also higher in the patients with MS, who also had lower exercise capacity and worse perception of well-being in 3 domains (physical function, vitality and social function) on the SF36 Questionnaire. MVA had higher specificity and positive predictive value in predicting outcome events, compared to mean gradient of 3 mmHg or 5 mmHg. Conclusions:

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In patients who had mitral valve repair for degenerative MR, MVA ≤ 1.5 cm2 occurs in about one-fifth of patients and is associated with adverse intracardiac hemodynamics, lower exercise

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capacity and adverse outcomes.

Key Words: Mitral valve insufficiency, mitral valve repair, mitral valve stenosis, exercise

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capacity, quality of life.

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Introduction We have demonstrated that some degree of mitral stenosis (MS) evidenced by elevated

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mitral valvular gradients following mitral valve (MV) repair for myxomatous/degenerative mitral regurgitation (MR) is not uncommon and is associated with functional significance.1 Mitral gradients are influenced by transvalvular flow and the duration of diastolic filling which is

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greatly dependent on heart rate. Mitral valve area (MVA) on the other hand is largely

independent of heart rate and is recommended to be the key measure in assessing the severity of

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MS. Severe MS is defined by MVA of ≤ 1.5 cm2 in the recent AHA/ACC Valvular Heart Disease Guideline.2 However, MVA has not been routinely measured and reported in patients following MV repair for degenerative MR. In this study, we sought to assess the prevalence and functional significance of MS defined by a calculated MVA of ≤ 1.5 cm2 and to assess different measures of mitral stenosis including MVA and mitral gradients in predicting adverse outcomes

Methods

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in patients following mitral valve repair for degenerative MR.

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The patient population has been previously described.1 Briefly, 110 patients who had MV repair for degenerative MR involving ≥ 2 mitral scallops were recruited between December

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2009 and April 2011. We excluded patients with greater than mild residual MR following repair, patients with aortic valve disease, patients with left ventricular dysfunction and patients who were unable to perform bicycle exercise test. The study was approved by our institutional review board, and informed consent was obtained in all patients. The patients underwent exercise echocardiogram using the supine bicycle protocol to assess exercise capacity and intracardiac hemodynamics including mitral valve gradients,

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severity of MR and pulmonary artery systolic pressure at rest and at peak exercise.3 The blood pressures and heart rates were also recorded at rest and at peak exercise. The patient also performed a 6-minute walk test. B-type natriuretic peptide (BNP) levels at rest and after exercise

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were measured. In addition the patient’s quality of life was assessed by the short form 36-Item Health Survey Questionnaire (SF36).

The resting and exercise hemodynamics were measured by Doppler echocardiography

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according to the recommendations of the American Society of Echocardiography.4 The

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modified Bernoulli’s equation was used to calculate the transmitral gradients, and the continuous equation to calculate the MVA by dividing the left ventricular outflow tract stroke volume by the integral of the diastolic transmitral velocity.5 The patients were divided into two groups based on the calculated resting MVA, namely > 1.5 cm2 (Group 1) and ≤ 1.5 cm2 (Group 2). This cut-

the recent guideline.2

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point (≤ 1.5 cm2) is the criterion of severe MS in patients with rheumatic mitral disease based on

Follow-up was performed in 2016 by a review of the electronic health record and a

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telephone interview. The outcome events were death from any cause, mitral valve surgery (repair or replacement) and heart failure requiring hospitalization or institution of heart failure

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therapy. Statistical Analysis

Data were imported and analyzed in SAS version 9.1 (SAS Institute Inc, Cary, NC).

Continuous variables were expressed as a mean + standard deviation whereas categorical variables were described as a percentage of the total. Continuous data were compared with a Student t test when normally distributed and with a Wilcoxon rank sum test when data were

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skewed. Categorical variables were compared with a Chi2 test or Fisher exact test, when count

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was <5.

Results

MS based on a calculated MVA ≤ 1.5 cm2 was present in 22 patients (20%), who had a

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longer time interval since surgery, were more symptomatic and more likely to have atrial

fibrillation.(Table 1) There were proportionally more women, lower body mass index and lower

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diastolic blood pressure. The body surface area was smaller in Group 2 due to the preponderance of women in the group. After indexing for body surface area, the index mitral valve area remained smaller in Group 2 compared to Group 1 (Table 2). In both groups, prolapse or flail of the posterior MV leaflet was prevalent and involvement of both leaflets in about half

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of the patients (Table 1). New York Heart Association Class was higher in Group 2. (Table 1) The resting and exercise echocardiographic and Doppler parameters are presented in Table 2. Resting measurements showed that Group 2 had larger indexed left atrial volume and

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left ventricular dimensions but a lower left ventricular stroke volume. Heart rate and left ventricular ejection fraction were similar in both groups. Group 2 patients had higher resting

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peak and mean mitral gradients and higher pulmonary artery systolic pressures. These hemodynamic differences were magnified by exercise with higher transmitral valvular gradients and higher pulmonary artery systolic pressures persisting in Group 2 patients. In Group 1, 3 additional patients developed mild MR at peak exercise. The details of the surgical technique used in the patients in the two groups are shown in Table 3. The vast majority of patients (107 of 110 patients) had annuloplasty with a complete

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ring or a posterior band. Sliding plasty was used more frequently in Group 1. A mitral annular band was more frequently employed than a complete ring in Group 1, and the reverse was present in Group 2. The annular ring size was similar between the 2 groups. The annular band

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was smaller in Group 2 patients, but the difference disappeared after indexing for body surface area (Table 3). The rings ranged 27 to 35 mm, and the bands 24 to 38 mm. There was good correlation between MVA and the size of ring (P=0.047) or band (P=0.003) and MVA was

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smaller in patients with ring than those with band (P<0.001) (Fig.1).

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Overall Group 2 patients had diminished exercise capacity as evidenced by 6-minute walk distance and exercise capacity measures on the supine bicycle test.(Table 4) There were higher baseline and post exercise BNP values in Group 2 patients than in Group 1 patients. Among the patient well-being measures determined by the SF-36 Questionnaire, three measures (physical function, vitality and social function) were lower in Group 2 patients and there were no

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SF-36 parameters that were better in Group 2 patients, compared to Group 1 patients. In our patients MVA of 1.5 cm2 corresponded to an approximate mean gradient of 5

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mmHg (Fig.2). Assessment of mitral hemodynamics was performed at 4.2 ± 2.3 years after surgery, and the outcome events assessed in a follow-up of 11.3 ± 2.3 year since surgery are

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shown in Table 5 for mean gradient > 3 mmHg, mean gradient > 5 mmHg and MVA ≤ 1.5 cm2. We included the mean gradient cutpoint of 3 mmHg based on our finding that patients with mean gradient > 3 mmHg had worse exercise capacity and exercise hemodynamics compared to those with mean gradient ≤ 3 mmHg.1 During follow-up, 2 patients died, 2 patients underwent mitral valve replacement and 7 patients developed heart failuire. All these measures had excellent sensitivity and negative predictive value, but MVA had a higher specificity and positive

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predictive value than the mean gradients (0.89 and 0.50 versus 0.35 and 0.15; 0.80 and 0.35 respectively).

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Discussion Prevalence of MS after MV Repair

In evaluating the result of MV repair, the focus has been on residual or recurrent MR.6-9

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Few studies examined the development of postoperative MS. In the study by Sakamoto et al, 105 patients underwent MV repair for degenerative disease with the use of an annuloplasty ring

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in 104 patients.9 The average mitral orifice area was significantly reduced after surgery but the severity of MS was reported to be mild. The MVA was 2.60±0.87 cm2 following posterior leaflet resection and 2.84±1.07 following anterior leaflet resection, compared to 3.60±0.92 cm2 and 3.48±0.95 cm2 respectively before the surgery.9 Thus it is quite certain that significant MS

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with MVA ≤ 1.5 cm2 was present in some of their patients but the clinical features and functional status of these patients were not presented. Riegel et al reported that 9 of 552 (1.6%) patients who underwent mitral repair required reoperation during the same admission, with 4 during the

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same operation due to restricted mitral leaflet motion, but in the other 5 patients the reasons for reoperation were unclear.10 The study included both patients with organic MR and functional

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MR. Annuloplasty with an annular ring was performed in 515 of 552 (93%) patients. The intraoperative peak and mean mitral gradients were significantly higher in the 9 patients who had reoperation compared to the rest of the patients (22.9±7.9 mmHg and 10.7±4.8 mmHg versus 7.6±3.7 mmHg and 2.9±1.6 mmHg). Seven of the 9 patients had MV repair for myxomatous MR. The intraoperative loading conditions were not provided to give a more proper interpretation of the mitral gradients, as many factors including heart rate impacted on the

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gradients.10 Nonetheless, these results showed that significant MS can occur shortly after MV repair and can result in early reoperation. It is plausible that MS albeit less severe may be

transmitral valvular gradients are common in this setting.1 Potential Causes of MS

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present in a larger proportion of these patients, supported by our observation that increased

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In the present study MS defined by a mitral valve area of ≤1.5 cm2 was present in onefifth of the patients following MV repair, and was more common in patients who had a complete

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annular ring. The mitral annular rings have smaller areas than the normal MVA of 4.0-5.0 cm2, and leaflet excision and plication may further limit the MVA, suggesting that some degree of MS may be inherent in the procedure of MV repair. This complication is less frequent but still occurs when the posterior annular band was used in place of a complete ring.

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The discrepancy between the calculated MVA using the continuity equation and the geometric MVA has been observed by Kubota et al in patients who had annuloplasty for ischemic MR and had normal mitral valve leaflets without thickening or commissural fusion.11

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The geometric area based on the dimension of the mitral annuloplasty ring or bands would suggest considerably larger MVA in these patients. They proposed that MS in these patients was

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largely due to restricted diastolic leaflet excursion rather than narrowing at the annulus. This mechanism may also be applicable in our patients whose posterior mitral leaflet frequently showed restricted excursion. Further studies into the mechanism of MS in this clinical setting are required to develop a better surgical strategy to prevent this complication, and real-time 3D echocardiography appears to be a promising imaging modality in this regard.12

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The longer time interval since surgery in Group 2 suggests that MS may be mediated by pannus formation at the annulus with extension onto the leaflets. This mechanism is unlikely because pannus is a late and rare occurrence.13-15In the study of Ibrahim and David, MS due to

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pannus formation was observed in 2 of 438 patients who had repair for degenerative MR at a mean follow-up of 66 months.15 On the other hand, MS in our patients and those reported by Sakamoto et al was present early in the follow-up generally within 6 months of surgery.9 The

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longer time interval since surgery in Group 2 could partly be explained by the increasing

tendency of our surgical team over the past decade to use a posterior band in preference to a

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complete ring in MV repair for degenerative MR. Sliding plasty of the posterior leaflet was less common in Group 2, raising the possibility that the height of the posterior mitral leaflet may

Significance of MVA

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contribute to the development of functional MS.

Although it is unclear whether MVA calculated by the continuity equation truly reflects

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the functional mitral orifice area in the setting of MV repair, the clinical significance of this measure is clear and well supported by our results. The hemodynamic measures in Group 2

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patients in response to exercise are what would be expected in patients with severe rheumatic MS.16,17 The functional significance of MVA in this clinical setting was further supported by the measurements of exercise capacity, BNP levels and the SF-36 Questionnaire. In addition, MVA predicted outcome events during follow-up with higher specificity and positive predictive value than the mean gradients of > 3 mmHg or > 5 mmHg.

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Limitations This is a single centre study and the number of patients was small. The outcome events

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were based on hospital record and telephone interview, such that mild heart failure may not be identified. There were more women in Group 2 with smaller body surface area, and this may partly account for the smaller MVA. MVA remained different between the 2 group after

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indexing for the body surface area. The smaller body surface area in Group 2 patients would have lessened rather than enhanced the hemodynamic and functional effects of a smaller MVA in

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Group 2 patients. Heart rates at rest and peak exercise were similar between the 2 groups. However mild MR was present in 13 of 88 Group 1 patients and 7 of 22 Group 2 patients (P=0.06), and this may have contributed to smaller stroke volume and MVA in the patients in the Group 2. The contribution was likely small because MR was only mild and the differences between the 2 groups persisted even after the 20 patients with mild MR were excluded from the

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analysis. The time interval since surgery was different between the two groups, partly due to the decreasing use of ring in the more recent MV repair patients. Nonetheless, it is possible that MS

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may be more frequent in Group 1 patients with a longer follow-up. Calculating MVA by the continuity equation during intra-operative TEE is problematic

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due to the usual suboptimal alignment of the left ventricular outflow tract. Although our results showed that MVA correlated closely with hemodynamic and functional measures, MVA by the continuity equation may not be a good measure to aid intra-operative decision making because it cannot be consistently measured intra-operatively. Mitral gradients alone may not be reliable because they are greatly affected by transvalvular flow and heart rate. MVA post MV repair may be measured intraoperatively by planimetry with the use of 3D echocardiography. Whether

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such measure correlates with MVA by the continuity equation during follow-up and whether it has similar clinical significance remain to be determined.

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The surgical technique of MV repair has been evolving at our centre. In our early experience, we primarily relied on the measurement of the intertrigonal distance for annuloplasty sizing which may have contributed to a smaller annular area. With the awareness of MS being a

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potential complication, annular bands are more frequently used, together with less aggressive leaflet resection and a greater use of artificial chords. Indeed we have launched a multi-centre

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randomized study to evaluate a more conservative surgical approach incorporating these modifications in preventing the development of MS.18 Conclusion

Following mitral valve repair for degenerative MR, MVA ≤ 1.5 cm2 can occur in about

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one-fifth of patients and is associated with a negative impact on intracardiac hemodynamics, exercise capacity and adverse events. MVA by the continuity equation should be measured during the follow-up of these patients. Further refinement in the repair technique to prevent this

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complication such as the use of an annular band instead of a complete ring and a greater degree

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of leaflet conservation will need to be studied.

Funding Source

Funding provided by University of Ottawa Heart Institute Academic Medical Organization.

Disclosure

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None.

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References: 1. Chan, K. L., Chen, S. Y., Chan, V., Hay, K., Mesana, T., & Lam, B. K. Functional

regurgitation. Circ Cardiovasc Imaging. 2013;6:1041-1047.

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significance of elevated mitral gradients following repair for degenerative mitral

2. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara

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PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Creager MA, Curtis LH, DeMets D, Guyton RA,

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Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Stevenson WG, Yancy CW; American College of Cardiology; American College of Cardiology/American Heart Association; American Heart Association.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

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Guidelines.J Thorac Cardiovasc Surg. 2014 Jul;148:e1-e132. 3. Henri C, Piérard LA, Lancellotti P, Mongeon FP, Pibarot P, Basmadjian AJ. Exercise testing and stress imaging in valvular heart disease. Can J Cardiol. 2014

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Sep;30:1012-26.

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4. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellika PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Soloman SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiograph. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association

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of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-63. 5. Quinones MA, Otto CM, Stoddard M,Waggoner A, ZoghbiWA. Recommendations

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for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of

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Echocardiography. J Am Soc Echocardiogr 2002;15:167-84.

6. Braunberger E, Deloche A, Berrebi A, Abdallah F, Celestin JA, Meimoun P, Chatellier

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G, Chauvaund S, Fabiani JN, Carpentier A. Very long-term results (more than 20 years) of valve repair with Carpentier’s techniques in nonrheumatic mitral valve insufficiency. Circulation 2001;104 (Suppl 1):I8-11

7. Gillinov AM, Cosgrove DM, Blackstone EH, Diaz R, Arnold JH, Lytle BW, Smedira NG, Sabik JF, McCarthy PM, Loop FD. Durability of mitral valve repair for

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degenerative disease. J Thorac Cardiovasc Surg. 1998 ;116:734-43. 8. Enriquez-Sarano M, Schaff H, Orszulak T, Tajik AJ, Bailey KR, Frye RL. Valve repair

1265.

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improves the outcome of surgery for mitral regurgitation. Circulation 1995;91:1264-

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9. Sakamoto Y, Hashimoto K, Okuyama H, Ishii S, Hanai M, Inoue T, Shinohara G, Morita K, Kurosawa H.Long-term assessment of mitral valve reconstruction with resection of the leaflets: triangular and quadrangular resection. Ann Thorac Surg. 2005 Feb;79:475-9.

10. Riegel AK, Busch R, Segal S, Fox JA, Eltzschig HK, Shernan SK.Evaluation of transmitral pressure gradients in the intraoperative echocardiographic diagnosis of mitral stenosis after mitral valve repair. PLoS One. 2011;6:e26559.

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11. Kubota K, Otsuji Y, Ueno T, Koriyama C, Levine RA, Sakata R, Tei C.. Functional mitral stenosis after surgical annuloplasty for ischemic mitral regurgitaton : importance

Thorac Cardiovasc Surg 2010;140:617-623.

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of subvalvular tethering in the mechanism and dynamic deterioration during exertion. J

12. Hung J, Lang R, Flachskampf F, Shernan SK, McCulloch ML, Adams DB, Thomas J, Vannan M, Ryan T. 3D echocardiography: a review of the current status and future

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directions. J Am Soc Echocardiogr 2007;20:213-233.

13. Tanaka K, Makuuchi H, Naruse Y, Kobayashi T, Hayashi I, Takayama T, Namifusa Y.

Surg (Torino). 2003;44:59-60.

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Mitral stenosis due to fibrous tissue overgrowth after mitral valve repair. J Cardiovasc

14. Nishida H, Takahara Y, Takeuchi S, Mogi K. Mitral stenosis after mitral valve repair using the duran flexible annuloplasty ring for degenerative mitral regurgitation. J Heart

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Valve Dis. 2005;14:563-4.

15. Ibrahim MF, David TE. Mitral stenosis after mitral valve repair for non-rheumatic mitral regurgitation. Ann Thorac Surg. 2002 ;73:34-6.

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16. Leavitt JI, Coats MH, Falk RH. Effects of exercise on transmitral gradient and

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pulmonary artery pressure in patients with mitral stenosis or a prosthetic mitral valve: a Doppler echocardiographic study. J Am Coll Cardiol 1991;17:1520-6.

17. Cheriex EC, Pieters FA, Janssen JH, de Swart H, Palmans-Meulemans A. Value of exercise Doppler-echocardiography in patients with mitral stenosis. Int J Cardiol 1994;45:219-26. 18. Chan V, Chu MWA, Leong-Poi H, Latter DA, Hall J, Thorpe KE, de Varennes BE, Quan A, Tsang W, Dhingra N, Yared K, Teoh H, Chu FV, Chan KL, Mesana TG, Connelly KA, Ruel M,

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Jüni P, Mazer CD, Verma S. Randomised trial of mitral valve repair with leaflet resection versus leaflet preservation on functional mitral stenosis (The CAMRA CardioLink-2 Trial).BMJ Open.

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2017;7:e015032.

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Table 1. Patient Characteristics

Group1

Group 2

(N=110)

MVA

MVA

> 1.5 cm2 (N=88)

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All

P

< 1.5 cm2 (N=22)

60 +/- 11.9

60 +/- 11.7

Male (%)

78 (71)

67 (76)

11 (50)

.02

1.92 +/-0.23

1.97 +/- 0.23

1.78 +/- 0.20

.0003

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Body surface area, m2

61.2 +/- 12.9

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Age, yrs

.37

29 (27)

23 (26)

6 (27)

.91

Chronic renal failure (%)

12 (11)

9 (10)

3 (14)

.70

Smoking (%)

60 (55)

49 (56)

11 (50)

.63

Atrial fibrillation (%)

18 (17)

13 (15)

5 (23)

.21

26.1 +/- 3.6

26.4 +/- 3.5

24.6 +/- 3.9

.03

131.7 +/- 17

132.5 +/- 16.7

128.5 +/- 19.6

.32

81.6 +/- 9.5

82.7 +/- 9.4

77.1 +/- 8.7

.02

109 (98)

88 (100)

21 (96)

.88

48 (44)

38 (43)

10 (46)

.85

4.2 +/- 2.3

3.8 +/- 2.2

6.4 +/- 0.93

<.0001

I

67 (61)

61 (69)

6 (27)

<.0001

II

33 (30)

21 (24)

12 (36)

.005

Body mass index Blood pressure, mmHg

Diastolic

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Systolic

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Hypertension (%)

Mitral leaflet pathology (%)

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Posterior Bileaflet

Time interval since surgery, yrs NYHA at follow-up (%)

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10 (9)

6 (7)

4 (18)

.002

Atrial fibrillation at follow-up

30 (27)

20 (23)

10 (46)

.03

Readmission

50 (45)

37 (42)

13 (59)

.15

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MVA, mitral valve area; NYHA, New York Heart Association.

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III

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Table 2. Echocardiographic Variables at Rest and at Peak Exercise Group1

Group 2

(N=110)

MVA Rest

MVA Rest

> 1.5 cm2

< 1.5 cm2

(N=88) Resting Measures 47.7 +/- 4.2

47.9 +/- 4.4

LVEDD Index, mm/m2

25.1 +/- 3.2

LVESD, mm

(N=22)

47.1 +/- 3.5

.48

24.6 +/- 3

26.9 +/- 3.5

.003

29.6 +/- 4.6

29.7 +/- 4.8

29.3 +/- 3.5

.69

LVESD Index, mm/m2

15.5 +/- 2.7

15.3 +/- 2.7

16.7 +/- 2.6

.03

LV EF, %

63.3 +/- 5.9

63.4 +/- 5.8

62.9 +/- 6.5

.39

LA Vol Index, ml/m2

39.5 +/- 12.7

37 +/- 10.7

49.8 +/- 14.8

<.0001

LV SV, ml

82.3 +/- 23.9

85.8 +/- 23.8

68.4 +/- 19

.001

LV SV Index, ml/m2

42.6 +/- 10.7

43.7 +/- 11

38.3 +/- 8.6

.03

5.8 +/- 1.6

6.1 +/- 1.5

4.8 +/- 0.9

.0002

3.0 +/- 0.7

3.1 +/- 0.8

2.7 +/- 0.5

.0002

72.3 +/- 10.8

72.3 +/- 10.3

72.1 +/- 12.8

.94

MV Peak Gradient, mmHg

10.0 +/- 4.4

8.7 +/- 3.0

15.4 +/- 5.2

<.0001

MV Mean Gradient, mmHg

4.5 +/- 2.4

3.9 +/- 1.6

7.1 +/- 3.5

<.0001

MV Area, cm2

2.1 +/- 0.6

2.3 +/- 0.5

1.3 +/- 0.2

<.0001

1.1 +/- 0.3

1.17 +/- 0.27

0.7 +/- 0.1

<.0001

20 (18)

13 (15)

7 (32)

.06

33.3 +/- 9.6

30.9 +/- 6.9

42.8 +/- 12.6

<.0001

120.9 +/- 24.2

122 +/- 22.6

116.4 +/- 30.3

.33

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CO, l/min CI, l/min/m2

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HR, bpm

MV Area Index, cm2/m2 MR (%)

PASP, mmHg

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LVEDD, mm

P

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All

Peak Exercise Measures Heart Rate, bpm

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MV Peak Gradient, mmHg

21.9 +/- 10.1

19.7 +/- 7.3

30.8 +/- 14.4

<.0001

MV Mean Gradient, mmHg

12.5 +/- 6.7

11.2 +/- 4.7

17.5 +/- 10.4

<.0001

23 (21)

16 (18)

7 (32)

.08

48.6 +/- 11.9

45.7 +/- 9

60.5 +/- 14.6

<.0001

MR (%)

RI PT

PASP, mmHg

AC C

EP

TE D

M AN U

SC

CI, cardiac index; co, cardiac output; EF, ejection fraction; LA, left atrium; LV, left ventricle; EDD, end diastolic dimension; ESD, end systolic dimension; MR, mitral regurgitation; MV, mitral valve; PASP, pulmonary artery systolic pressure; SV, stroke volume.

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Table 3. Surgical Characteristics Group1

Group 2

(N=110)

MVA

MVA

> 1.5 cm2

< 1.5 cm2

(N=88) Posterior mitral valve 79 (72)

63 (72)

Plication (%)

8 (7) 65 (59)

16 (72)

.92

6 (7)

2 (9)

.71

58 (66)

7 (32)

.004

M AN U

Sliding plasty (%) Anterior mitral valve

P

(N=22)

SC

Resection (%)

RI PT

All

11 (10)

10 (11)

1 (5)

.69

A2 repair (%)

43 (39)

32 (36)

11 (50)

.24

A3 repair (%)

23 (21)

19 (22)

4 (18)

.73

4 (4)

4 (5)

0

.58

5 (5)

4 (5)

1 (5)

.99

20 (18)

16 (18)

4 (18)

.99

107 (97)

85 (97)

22 (100)

.38

65 (59)

60 (68)

5 (23)

<.0001

30.7 +/- 2.8

30.9 +/- 2.8

28.4 +/- 2.6

.03

16.1 +/- 2.2

17.1 +/- 2.7

0.42

42 (38)

25 (28)

17 (77)

<.0001

30.4 +/- 2.1

30.2 +/- 1.8

29.6 +/- 2.2

.20

15.4 +/- 1.8

16.5 +/- 1.5

0.44

Commissuroplasty Anterolateral (%)

Artificial chords

EP

Posteromedial (%)

TE D

A1 repair (%)

MV Annuloplasty (%)

AC C

Band (%)

Mean band size, mm

Indexed band size, mm/m2 Ring (%)

Mean Ring Size, mm Indexed ring size, mm/m2

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Tricuspid valve repair (%)

10 (9)

6 (7)

4 (18)

AC C

EP

TE D

M AN U

SC

RI PT

Indexed band size and ring size were obtained by dividing the dimension of the device by the body surface area.

.09

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Table 4. Functional Variables

Group1

(N=110)

MVA > 1.5 cm2

P

< 1.5 cm2 (N=22)

459 +/- 90

474.5 +/- 77.6

400.3 +/- 112.5

.0004

12.8 +/- 2.8

13.7 +/- 5.5

9.2 +/- 4.9

.0006

108.1 +/- 44.9

115.4 +/- 44.1

78.9 +/- 35.8

.0005

5.8 +/- 1.7

5.9 +/- 1.7

5.1 +/- 1.4

.03

BNP baseline

93.4 +/- 89

82.2 +/- 87.4

138.1 +/- 82.9

.008

BNP exercise

118.8 +/- 97.5

109.4 +/- 100

156.2 +/- 77.7

.04

81.5 +/- 20.4

84.2 +/- 18.4

70.7 +/- 24.4

.005

61 +/- 21

63.5 +/- 20.4

50.7 +/- 20.9

.01

86.9 +/- 22

89.1 +/- 18.6

78.4 +/- 31.4

.02

Cycle ergometry

M AN U

Exercise Duration, min Exercise, W Exercise, METS

Physical function Vitality Social function

EP

BNP levels, pg/ml

SF36

SC

6-Minute Walk Distance, m

MVA

TE D

(N=88)

Group 2

RI PT

All

AC C

BNP, B-type natriuretic peptide; SF36, short-form 36 Item Health Survey.

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Table 5. Outcome Events during Follow-up* Mean gradient, mmHg >3 ≤5 75 79

0 0 0

RI PT

≤3 >5 35 31 Number of Patients Outcomes 0 2 0 2 Death 0 2 0 2 MV surgery 0 7 0 7 CHF CHF= congestive heart failure; MV=mitral valve; MVA=mitral valve area.

MVA, cm2 > 1.5 ≤ 1.5 88 22

AC C

EP

TE D

M AN U

SC

*These represented the number of events and not the number of patients, as some patients had multiple outcome events.

2 2 7

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Figure Legend: Figure 1. Correlations between mitral valve area (MVA) and the sizes of annular ring and band following

RI PT

mitral valve repair for degenerative mitral regurgitation. Figure 2. Correlation between mitral valve area and mean mitral diastolic gradient in 110 patients

AC C

EP

TE D

M AN U

SC

following mitral valve repair for degenerative mitral regurgitation.

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Figure 1.

4

RI PT

3.5 3 2.5 2 1.5 1 0.5 0 20

22

24

26

28

30

SC

MVA at Rest (cm2)

4.5

32

34

M AN U

Annuloplasty Size (mm)

AC C

EP

TE D

Band

Ring

36

38

40

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AC C

EP

TE D

M AN U

SC

RI PT

Figure 2.

AC C

EP

TE D

M AN U

SC

RI PT

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AC C

EP

TE D

M AN U

SC

RI PT

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