Long-term clinical and echocardiographic results after successful mitral balloon valvotomy and predictors of long-term outcome
Mohamed Eid Fawzy1,*,
Hesham Hegazy1,
Mohamed Shoukri2,
Fayez El Shaer1,
Abdulmoneim ElDali2 and
Mohammed Al-Amri1
1Department of Cardiovascular Diseases (MBC-16), King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 11211, Saudi Arabia
2Biostatistics, Epidemiology and Scientific Computing Department, King Faisal Specialist Hospitaland Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia
Received 14 September 2004; revised 13 February 2005; accepted 17 February 2005; online publish-ahead-of-print 8 April 2005.
* Corresponding author. Tel: +966 1 474 7272; fax: +966 1 442 7482. E-mail address: fawzy100{at}hotmail.com
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Abstract
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Aims To assess the long-term outcome of mitral balloon valvotomy (MBV) and identify predictors of restenosis- and event-free survival.
Methods and results We report the immediate and long-term clinical and echocardiographic results in 493 patients, mean age 31±11, who underwent successful MBV and were followed-up for 0.515 years (median 5±3) with clinical and echocardiographic examination. After MBV, mitral valve area increased from 0.84±0.2 to 1.83±0.53 cm2 (P<0.0001) as measured by catheter and from 0.92±0.17 to 1.96±0.29 cm2 as measured by two-dimensional echo. Restenosis occurred in 86/493 (17.4%) patients and it was less frequent in patients with low echo score. Actuarial freedom from restenosis at 5, 7, 10, and 13 years were 89±1, 81±2, 68±3, and 51±6%, respectively, and was significantly higher in patients with low echo score. Event-free survival (death, redo MBV, mitral valve replacement, New York Heart Association functional Class III or IV) at 5, 7, 10, and 13 years were 92±1, 87±2, 80±3, and 74±3%, respectively, and was significantly higher for patients with low echo score. Cox regression analysis identified mitral echocardiographic score (MES) >8 as predictors of restenosis (P=0.0004) and MES and age as predictors of event-free survival (P=0.0003 and 0.004, respectively).
Conclusion MBV has excellent long-term results for selected patients with mitral stenosis. The long-term outcome after this procedure can be predicted from baseline clinical and valvular characteristics.
Key Words: Rheumatic heart disease Mitral valve Valvuloplasty
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Introduction
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Since its introduction in 1984 by Inoue et al.,1 mitral balloon valvotomy (MBV) has emerged as the treatment of choice for severe pliable rheumatic mitral stenosis (MS). Although numerous studies have documented favourable immediate and intermediate follow-up results,17,1013,15 long-term echocardiographic follow-up studies of MBV are few.14,1619 In the present study, we report on the immediate and long-term clinical and echocardiographic follow-up results of 493 patients who underwent successful MBV in our hospital. Analysis of these data allows the identification of factors that influence the long-term outcome.
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Methods
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Study population
Between December 1989 and December 2003, 524 consecutive patients with severe MS underwent MBV as first procedure, patients who had previous surgery or balloon valvotomy are not included in this study. Their baseline characteristics are described in Table 1. On the basis of immediate results, the procedure was successful in 504 (96%) patients and unsuccessful in the remaining 20 patients [severe mitral regurgitation (MR) in nine patients, 11 patients had post-procedure mitral valve area (MVA) <1.5 cm2 all of them had echo score >8]. These 20 patients were excluded from further analysis. Successful results were defined as post-procedure MVA
1.5 cm2 as assessed by echocardiography and no MR grade>2/4 according to Sellers classification.8 Eleven patients who came from neighbouring countries were lost to follow-up. The remaining 493 patients (98% of the 504 eligible patients) were followed-up for a 0.515 median 5 years and are the subject of this report. Written informed consent was obtained from all patients prior to MBV.
Echocardiographic and Doppler examination
Two-dimensional echocardiography (2D echo) and Doppler echocardiographic studies were performed 12 weeks before the procedure using commercially available equipment (HewlettPackard Unit Sonos 1500 and 5500). In addition to the mean transmitral valve gradient, the MVA was calculated from the Doppler study using the pressure half-time method and also by planimetry using the short axis 2D echo view. Pulmonary artery systolic pressure was estimated by continuous wave Doppler echocardiography using the modified Bernoulli equation [4x(peak tricuspid regurgitant jet velocity)2] with 10 mmHg added for the estimated right atrial pressure. The morphologic features of the mitral valve were semiquantitated according to the mitral echocardiographic score (MES) as described by Wilkins et al.9 The mitral valve morphology was considered favourable if the MES
8 and unfavourable if MES>8. The echo Doppler studies were repeated immediately after MBV, 6 months and annually thereafter up to 15 years. Transesophageal echocardiogram (TEE) was carried out before MBV for patients with AF or history of systemic embolism or obese patient (weight
80 kg) when the left atrium is not properly visualized.
Mitral balloon valvotomy
All patients underwent MBV using the stepwise Inoue's balloon technique as described previously.6,7 Standard haemodynamic measurements of the right and left heart pressures included simultaneous measurements of left atrial and left ventricular pressures, mean mitral gradient and MVA calculated using the Gorlin formula, cardiac output was determined by the Fick or thermodilution method. All haemodynamic measurements were obtained before and immediately after MBV. A computer (Micro-Siemens-Elema AB, Solna, Sweden) was used for the calculation of the haemodynamic parameters. Left ventriculography was performed before and after MBV to assess the presence and severity of MR using the Sellers classification.8
Follow-up
Clinical and echocardiographic assessments were carried out 6 months after MBV and annually thereafter for up to 15 years. Event-free survival was assessed [events were defined as death from all cause, mitral valve replacement (MVR) or repeated MBV, New York Heart Association (NYHA) functional Class III or IV]. Restenosis following valvotomy (defined as loss of >50% of the original increase in MVA, with follow-up MVA<1.5 cm2) was also examined. Clinical evaluation was accomplished by direct interview of the patient at clinic visits. Follow-up was concluded in January 2005.
Statistical analysis
Invasive and echocardiographic data obtained before and immediately and long-term after MBV were compared using the Student's t-test (paired, two-tailed) for continuous data. Spearman's rank correlation (r) was used to measure the correlation between variables. KaplanMeier estimates were used to determine freedom from restenosis and event-free survival for the whole group and for patients with MES
8 and >8, respectively (survival with freedom from redo MBV, MVR or cardiac death or NYHA functional Class III or IV), only patients with successful MBV were included in the analysis. The survival curve between groups were compared using the log-rank test. Stepwise Cox multivariable regression analysis was used to identify predictors of restenosis and event-free survival. (The assumption of proportionality of hazard was assessed using CoxSnell residuals. The log-negativelog of the survival function plot was a straight line ensuring the validity of the proportionality assumption). The variables included in the analysis were age, sex, atrial fibrillation (AF), MES, prevalvotomy NYHA functional class, and pre- and post-procedure values for MVA and pulmonary artery pressure and moderate MR. Descriptive statistics for the continuous variables are reported as median±1 inter-quartile range. The type I error rate was set at
=0.05. Controlling the type I error at the nominal 0.05 level was achieved using Bonferroni's correction as a result of multiplicity. All data were entered prospectively in a computerized database beginning 1989. Analysis was performed with SAS Statistical Software (SAS version 8, Statistical Analysis System SAS Institute Inc., Cary, NC, USA).
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Results
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Immediate haemodynamic results
The left atrial pressure, mean mitral gradient, pulmonary artery systolic pressure decreased significantly after MBV with corresponding increase in MVA from 0.84±0.2 to 1.83±0.53 cm2 (P<0.0001) as measured by catheter (Table 2) and from 0.92±0.17 to 1.96±0.29 cm2 (P<0.0001) as measured by 2D echo (Table 3). A significant inverse relationship was found between MES and post-procedure MVA (r=0.33; P<0.0001); patients with MES
8 had larger immediate valve area whether measured by catheter 1.92±0.53 cm2 (P=0.02) or 2D echo 2±0.3 cm2 (P=0.009). Also there was good correlation between post-procedure Doppler MVA and 2D echo MVA (r=0.55; P<0.0001). MR was absent after the procedure in 338 patients and was recorded as grade 1 in 126 patients, grade 2 in 40 patients.
Complications
The incidence of major adverse in-hospital events are shown in Table 4. There were no in-hospital deaths. Pericardial tamponade occurred in four patients and they underwent pericardiocentesis in the catheterization lab; and MBV was carried out successfully a few months later. Cerebrel thromboembolic events occurred in three patients, all of whom were in AF. All were taking warfarin before the procedure and TEE was not carried out before the procedure for these three patients. One of these patients recovered completely and two patients developed stroke. Atrial septal defect was detected by echo colour flow mapping immediately after MBV in 116 patients (23%).
Clinical and echocardiographic follow-up
Eleven patients were lost follow-up came from neighbouring countries (these 11 patients had similar demographic characteristics to the rest of the study population mean age 32±10 years and echo score 7.8±1 and immediate MVA 1.92±0.26 cm2). The remaining 493 patients (98% of the eligible) were followed-up at clinic visits with clinical and echocardiographic examination for a period 0.515 (median 5) years. The MVA at last follow-up was 1.7±0.39 cm2. It was larger in patients with favourable mitral valve morphology (MES
8) 1.8±0.37 cm2 (P=0.004). Left atrial size as determined by echocardiographic anteriorposterior dimension was 48±7.6 mm at baseline, a significant reduction in left atrial dimension was observed at follow-up to (43.7±7.2 mm) P<0.0001 (Table 3). New onset AF was encountered in 26 patients (5%) at follow-up and the prevalence of AF was 90/493 (18%) (Table 3).
Regression of pulmonary hypertension
Comparison of values for systolic pulmonary artery pressure obtained by Doppler before valvotomy to those seen at follow-up demonstrated a significant regression of pulmonary hypertension overtime. The pulmonary artery systolic pressure fell from 48.6±17.4 mmHg before MBV to 31±10 mmHg at follow-up (P<0.0001).
Restenosis
Restenosis was encountered in 86 out of the 493 patients (17.4%) who had successful MBV and occurred less frequently in patients with MES
8 (12.4%). Stepwise Cox multivariable regression analysis identified MES as predictor of restenosis (P=0.0004). The estimated restenosis-free survival for the whole population and patients with MES
8 and >8 is depicted in Figure 1. Only patients with successful MBV were included in the analysis. Values for actuarial freedom from restenosis at 5, 7, 10, and 13 years for the whole population study were 89±1, 81±2, 68±3, and 51±6%, and were significantly higher for patients with MES
8: 93±1, 88±2, 78±3, and 63±6%, respectively (P<0.0001).

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Figure 1 Freedom from restenosis by KaplanMeier estimates for all patients and for patients with MES 8 and >8. Numbers at the bottom represent patients alive and uncensored at each year of follow-up.
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Follow-up events
Four deaths occurred at follow-up, two deaths after MVR, one patient died after large cerebral infarction following cerebral embolism in the patient with AF, and one patient died following status epilepticus not related to the patient's cardiac condition. Fourty-eight out of 86 patients who developed restenosis underwent reintervention for severe symptomatic restenosis (redo MBV 30 patients and MVR 18 patients), eight patients were in NYHA functional Class III are waiting for reintervention. The remaining 30 patients with restenosis were asymptomatic and their MVA was not critical (>1.2 cm2). The event-free survival at 5, 7, 10, and 13 years for the whole study population was 92±1, 87±2, 80±3, and 74±3%, and was significantly higher for patients with MES
8: 95±1, 91±2, 86±3, and 84±3%, respectively (P=0.0004). The predictors of event-free survival were low echo score and age (P=0.0003 and 0.004, respectively).
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Discussion
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Several studies have described the salutary immediate and mid-term results of balloon valvotomy for severe MS.17,1012,15 However, long-term echocardiographic follow-up studies of MBV are few.14,1619 This study provides a longer follow-up period compared with other studies.1318
Immediate results
There was a significant inverse relationship between the MES and post-procedure MVA and mitral valve morphology was the best predictor of post-procedure mitral opening, a finding concurring with the reports of other investigators.9,1419 However, good results could also be obtained in cases with relatively high echo score. Some increase in MR immediately post-valvotomy was frequent but severe MR was rather uncommon in our series and occurred mainly in patients with high echo score.
Restenosis
The restenosis rate in this series (17.4%) and was lower in patients with low echo score. Restenosis rate after MBV has been reported to range from 3 to 70% at 13 years.1113 The restenosis-free probability is 81% at 7 years, 68% at 10 years, and 51% at 13 years and concur with the report by Ben Farhat et al.18 [80% at 7 years and 66% at 10 years in young population (mean age 33±13 years, similar to our patients)]. Hernandez et al.17 on the other hand reported a 39% restenosis rate at 7 years in older patients (mean age 53 years). In this series, the predictors of being free from restenosis were a low echo score, findings that concur with reports of other investigators.5,9,11,1419
Event-free survival
The event-free survival at 5, 7, 10, and 13 years for the overall study population with successful MBV were 92±1, 87±1, 80±3, and 74±3%, respectively and were significantly higher for patients with MES
8 (Figure 2). These findings concur with the report of Ben Farhat et al.18 Long-term event-free survival data have been reported by other investigators, Cohen et al.14 found a 51% event-free survival at 6 years in 146 patients (mean age 59 years, MES 7.7). Iung et al.16 reported an event-free survival rate of 61% at 10 years in 528 patients with successful MBV (mean age 49 years). Hernandez et al.17 (561 patients with successful procedure, mean age 53 years) reported an event-free survival rate of 69% at 7 years for the whole group and 88% for their subgroup with low MES. Palacios et al.19 (879 patients with successful procedures, mean age 55 years) described a rate of 38 and 22% at 12 years for patients with MES
8 and >8, respectively. Differences in age, clinical characteristics, and valve morphology may account for the lower long-term event-free survival in the above reports from the USA and Europe when compared with our patients in this series. It is important to emphasize that patients with low score had a high probability of being event-free at 10 years (86%).

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Figure 2 KaplanMeier event-free survival estimates (alive and free of redo MBV, MVR, NYHA III or IV) for all patients and for patients with MES of 8 and >8. Numbers at the bottom represent patients alive and uncensored at each year of follow-up.
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Regression of pulmonary hypertension
Severe pulmonary hypertension is present in a large proportion of patient with severe MS. As previously demonstrated by us, severe pulmonary hypertension is present in 38% of the patients with severe MS. Immediately following valvotomy, pulmonary hypertension decreases slightly with further substantial regression occurring over time, a finding consistent with the results of previously reported studies.2022
Regression of left atrial size
Significant reduction of LA size occurs following successful mitral valvotomy. These findings further support previous report by us demonstrating reduction of LA size after successful MBV.23 New onset of AF post-MBV was encountered in 26 patients (5%) and prevalence of AF at follow-up was 90/493 (18%). This figure is much lower when compared with the findings reported by Diker et al.24 where they reported 29% incidence of AF in patients with isolated MS with similar baseline characteristics to our patients (mean age 37.8±15) year.
Limitation of the study
A limitation of the present study is 11 patients lost follow-up. They came from neighbouring countries; however, they have similar demographic characteristics when compared with the rest of the population and the immediate result after MBV were also similar. The findings in this series were observed in a population of young patients and, thus, cannot be extrapolated to older patients.
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Conclusions
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MBV has excellent long-term results in patients with favourable mitral valve morphology but those with less favourable anatomy may still have reasonable good haemodynamic and symptomatic relief. The long-term outcome after this procedure can be predicted from baseline clinical and valvular characteristics.
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Acknowledgement
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We thank Lydia B. Robosa for secretarial assistance.
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