Introduction
Rheumatic valvular disease continues to be prevalent in developing countries, with mitral stenosis being the most frequent valve disorder 1. During the past two decades, percutaneous mitral valvuloplasty (PMV) has emerged as the procedure of choice in most patients with symptomatic mitral stenosis 2. Several large series reported an excellent outcome both on the short and long run 3-7, as well as a low incidence of serious complications 8. Moreover, in patients with mitral valve morphology suitable for balloon valvuloplasty, results of randomized trials comparing PMV with surgical commissurotomy (both open and closed) have demonstrated comparable clinical, echocardiographic, and hemodynamic outcome between the two therapeutic strategies, in addition to shorter hospital stay and lower morbidity and mortality in the setting of PMV 9-13.
Late recurrence of symptoms after PMV is chiefly related to mitral restenosis 6. The incidence of restenosis varies widely among centers and techniques, but is reported to approach 40% at 7 years follow-up 14. A few

reports are available about redo PMV; however, they demonstrate encouraging results in selected patients with favorable characteristics 15. In a retrospective study design, we tried to explore the immediate results of redo PMV in comparison with initial PMV.
Methods
Patient selection:
We included 30 consecutive patients with symptomatic moderate to severe mitral stenosis (group A) [defined as mitral valve area (MVA) <1.5 cm2] and 40 consecutive patients with symptomatic moderate to severe mitral restenosis after successful initial PMV (group B) [defined as a MVA <1.5 cm2 and loss of >50% of the initial gain of valve area by the first PMV], admitted to our cath labs during the period from May 2006 to April 2007, to undergo PMV. Patients were considered eligible for enrollment if they had no more than grade 2/4 mitral regurgitation (MR) by echocardiography. We excluded patients with unfavorable mitral valve morphology [defined as a Massachusetts General Hospital (MGH) score ≥12], patients with previous

.

Correspondence:Dr Wail Nammas, Cardiology Department, Ain Shams University Hospitals, Faculty of Medicine, Ain Shams University. Abbassia, Cairo, Egypt. P.O. 11381
E-mail: wnammas@hotmail.com

surgical mitral commissurotomy, patients with concomitant valve disease that needs surgical intervention, patients indicated for coronary artery bypass surgery, and patients with limited life expectancy due to coexistent disease (for example: malignancy). Before inclusion, an informed consent was obtained from each patient and the study protocol was reviewed and approved by our local institutional human research committee as it conforms to the ethical guidelines of the 1975 Declaration of Helsinki as revised in 2002.
Echocardiographic Assessment:
Assessment of the mitral valve was performed in all patients by trans-thoracic echocardiography within 24 hours after admission. Doppler echocardiography was performed using a General Electric Vivid 7 Pro cardiac ultrasound machine (General Electric, Norway). A 2.5 MHz phased array probe was used to obtain standard 2D, and Doppler images. Patients were examined in the left lateral recumbent position using standard parasternal and apical views. MVA was assessed by planimetery method in the parasternal short axis view. Mean diastolic pressure gradient across the MV was measured from Doppler spectral analysis of diastolic mitral flow in the apical 4 chamber view. Semi-quantification of MR grade was obtained by color flow mapping of MR jet using Helmcke classification 16.
Scoring of the mitral valve was done by the Massachusetts General Hospital (MGH) scoring system 17. Left atrial diameter was measured in parasternal long and short axis views. Other chamber size was also assessed as well as other valve abnormalities.
Immediately before the procedure, all patients underwent trans-esophageal echocardiographic assessment using the same cardiac ultrasound machine (General Electric, Norway). Image acquisition was performed with a trans-esophageal 5 MHz multi-plane phased array probe at mid-esophageal level. Assessment was done in the standard way to exclude the presence of thrombi in the left atrium or left atrial appendage, to measure mitral annular diameter and interatrial septal thickness.
Percutaneous Mitral Valvuloplasty:
PMV was performed by the antegrade trans-septal approach using either the standard single balloon technique described by Inoue and colleagues 18 or the multi-track technique based on the method described by Benhoffer et al 19. Balloon size was chosen according to the usual method for the Inoue technique, while for the multi-track technique, it was based on the mitral annular diameter (measured by echocardiography) as follows: sum of diameters of the two balloons equals mitral annular diameter. Right and left heart hemodynamic data were recorded before and after the procedure. Adequate result was assessed in the cath lab by invasive measurement of the mean diastolic pressure gradient across the mitral valve.

Patient assessment by trans-thoracic echocardiography was repeated 48 hours following the procedure to evaluate final MVA (by planimetery method), mean diastolic pressure gradient across the mitral valve, and the presence and grade of MR, if any.
Definitions:
Procedural success was defined as an increase of 50% or more of MVA with a final MVA ≥1.5 cm2, without major complications. Major complications were defined as the occurrence of any of the following: more than grade II MR, cerebrovascular stroke, cardiac tamponade or periprocedural death. Restenosis was defined as loss of >50% of the initial gain of valve area by the preceding PMV with a final MVA <1.5 cm2.
Statistical Analysis:
All continuous variables were presented as mean ± SD, if they were normally distributed. Differences in the normally distributed variables were assessed using the t-test and the paired t-test for dependent variables. Categorical variables were described with absolute and relative (percentage) frequencies. Pearson χ2 and un-paired t tests were used to compare the distribution of categorical and continuous variables, respectively, between the two individual study groups. Pearson’s correlation coefficient was used to study the relationship between the final MVA and the initial MGH score of the mitral valve in either group. All tests were two-sided and a probability value of P<0.05 was considered statistically significant. Analyses were performed with SPSS version 12.0 statistical package (SPSS Inc., Chicago, IL, USA).

Results
A total of 70 patients including 30 consecutive patients with moderate to severe de novo mitral stenosis (group A) and 40 consecutive patients with moderate to severe mitral restenosis after initial PMV (group B) were enrolled in the current study. The mean age of the study population was 33.7 ± 6 years, 25.7% (18 patients) being males. Eighteen patients (25.7%) were in atrial fibrillation. In group B, the mean time from the initial PMV to redo PMV was 5.8 ± 2.2 years. No patient had any sign of rheumatic activity between the initial and redo procedure. Table 1 shows baseline clinical characteristics and initial echocardiographic findings of the 2 individual study groups. No statistically significant difference was found between the two groups concerning any of the baseline clinical or initial echocardiographic characteristics except for atrial fibrillation which was found more frequently in group B in comparison to group A [15(37.5%) versus 3(10%) respectively, p<0.05].

In group A, the procedure was performed by the multi-track technique in 23 (76.7%) and by the Inoue technique in 7 (23.3%) patients, while in group B, the procedure was performed by the multi-track technique in 25 (62.5%) and by the Inoue technique in 15 (37.5%) patients (p>0.05). According to our definition, procedural success was achieved in 28 (93.3%) patients in group A, and in 37 (92.5%) patients in group B (p>0.05). Table 2 shows post-procedural hemodynamic and echocardiographic data of the 2 individual study groups. No statistically significant difference was found between the two groups concerning any of the parameters of immediate procedural outcome (p>0.05 for all).

Table 1 Baseline clinical characteristics and initial echocardiographic findings of the 2 individual study groups

Table 2 Post-procedural hemodynamic and echocardiographic data of the 2 individual study groups

In group A, one patient (3.3%) developed cerebrovascular stroke immediately following the procedure and died 2 days later. This patient had atrial fibrillation, but had no thrombi shown by trans-esophageal echocardiography the day before the procedure. He received the usual dose of heparin after trans-septal puncture (5 000 IU), and had a normal procedure duration (45 minutes). One patient (3.3%) had a suboptimal final MVA after the procedure. Another patient in group A developed a puncture site hematoma, and another developed rapid atrial fibrillation that required electrical cardioversion. In group B, two patients (6.7%) developed severe MR: one of them had grade IV MR and consequently required emergency mitral valve replacement, and the other had grade III MR and was treated conservatively. Similar to group A, one patient (3.3%) had a suboptimal

final MVA after the procedure. One patient in group B developed ventricular tachycardia treated by electrical cardioversion, one developed allergic drug reaction and another developed vasovagal reaction. There were no cases of cardiac tamponade, and no cases required blood transfusion or peripheral vascular repair.
          There was a significant negative correlation between the final MVA following the procedure and the initial MGH score of the mitral valve, in both group A and B (correlation coefficient r = -0.441 and -0.397 respectively, p<0.05 for both).
Discussion
          The current study is the first to present a direct head-to-head comparison between the outcome of redo PMV for patients with mitral restenosis after successful initial PMV, and that of first PMV in patients with de novo mitral stenosis, in a retrospective study design. It demonstrated that redo PMV can be safely performed in selected patients, with an immediate procedural success of 92.5%, an adequate final MVA comparable to that of first PMV (with a gain of MVA similar to that of first PMV), and a relatively low complication profile, quite comparable to that of first PMV.
Treatment strategies for mitral restenosis:
          The chief cause of functional deterioration after successful percutaneous or surgical mitral commissurotomy is valve restenosis 20-24. The reported rate of restenosis varies widely among series; however, approximately 7% to 21% of patients develop recurrent symptoms after successful percutaneous procedure 9,25-28. Owing to the extensive valve deformity commonly found in these patients, mitral valve replacement is often performed 29. However, mitral valve replacement carries a higher risk of morbidity and mortality, as compared to surgical commissurotomy. Moreover, the problems related to the valve prosthesis worsen the long-term outcome. Yet, a few data are available about open mitral commissurotomy for mitral restenosis 15. Formerly, closed mitral commissurotomy was shown as an effective option for restenosis following an initial closed commissurotomy, particularly, in young patients with pliable valves 20. Recently, PMV has emerged as a therapeutic option for symptomatic mitral restenosis, with promising mid-term outcome, especially, in patients with favorable characteristics 15.

Immediate outcome of redo PMV:
The immediate procedural success rate in the group of restenosis compared favorably with that of the group of de novo mitral stenosis (92.5% versus 93.3% respectively). Additionally, it compares well with that previously reported by Iung et al 15 and is far better than that of Pathan et al 30 (91% and 75% respectively). In fact, the lower success rate in the later series could be attributed to a greater extent of valve pathology (higher MGH score and more calcification) and less favorable patient characteristics (older age, more atrial fibrillation and history of surgical commissurotomy) 30. Young age (in our series 33.7 ± 6 years) is a known strong predictor of good immediate outcome of PMV 5,7. In contrast, patients with atrial fibrillation are at a higher risk of poor outcome 24,31. In our series, atrial fibrillation was significantly more prevalent in group B in comparison to group A (p<0.05). This may have contributed to the higher rate of severe MR (6.7%) after the redo procedure; nevertheless, the overall success rate was similar to the other group, as mentioned before. The outcome of redo PMV would have been better should the two groups have had similar patient characteristics.

The safety of PMV was formerly demonstrated in several large series 5,7,25. In the current series, severe MR occurred in 6.7% of patients in group B, while no patient in group A had severe MR. Although it is difficult to compare the results of redo PMV with those of initial PMV due to obvious patient heterogeneity, repeated valve injury and healing process due to multiple interventions may be an adding factor in this scene 30. The occurrence of stroke in one patient in group A (3,3%) may express the unpredictable nature of this complication. This patient had atrial fibrillation; however, he had no thrombi by trans-esophageal echocardiography. This may justify the view that redo PMV should be performed only in symptomatic patients 15.
We excluded patients with MGH score ≥12, and as shown in table 1, MGH score was quite similar between the two groups (7.7 ± 1.2 and 7.7 ± 1.6 for groups A and B respectively). The favorable mitral valve morphology (based on MGH score in our series) may have well participated to the relatively high procedural success rate in both groups. Recent reports have emphasized the importance of commissural morphology (chiefly commissural calcification) and subvalvular involvement in determining immediate outcome of PMV 32-34. More recently, a novel scoring system was suggested based only on these 2 parameters and better predicted immediate outcome after the procedure 35. Excluding other parameters (namely, leaflet thickness and mobility) not closely related to the outcome of PMV would have further improved the immediate success rate of the procedure in the current series (92.5%).
Clinical Implications:
The feasibility of redo PMV with a relatively high procedural success rate and an acceptable complication profile - as compared to first PMV for de novo mitral stenosis – makes it an appealing therapeutic strategy for patients with recurrent valve stenosis. In these patients, the procedure of redo PMV would constitute a suitable alternative to surgery on the long-term. This might be particularly attractive in young females with child-bearing potential, in order to defer the need for valve replacement. Over and above, it might serve as an acceptable approach to avoid surgery in selected patients with high operative risk.
Conclusions:
The procedure of redo PMV for patients with mitral restenosis after initial successful PMV is feasible with a high procedural success rate, and can be accomplished at a low complication profile, that favorably compare with those of PMV performed for patients with de novo mitral stenosis.

Limitations of the study:
          Our findings are based on a single center study with a relatively small sample size of the cohort, a fact that makes it difficult to generalize our results to all patients with mitral restenosis. Multicenter studies using the same protocol and examining a larger number of patients are needed before reaching solid conclusions. Moreover, our patients underwent PMV with either the Inoue technique or the multi-track techniuqe, and it is unknown whether our data can be safely extrapolated to patients undergoing the double balloon technique and patients undergoing percutaneous metallic valvotomy. Additionally, success rates were defined based on echocardiographic data irrespective of hemodynamic data. Furthermore, comparative follow-up of both groups in our series, is necessary to determine outcome on the intermediate and long term (follow-up is already underway). Additionally, patients in our series are relatively young with a favorable MGH score. Our data may not be applicable to older patients with less favorable valve characteristics.Finally, selection of patients with mitral stenosis did not employ the recently ascertained determinants of outcome such as commissural calcification, a fact that may certainly influence outcome.

Acknowledgement
We would like to express our deep gratitude to all the staff members of the cath labs in cardiology department, Ain Shams University Hospitals; who have sincerely and rigorously supported the performance of this work.

References
1.Carroll JD, Feldman T. Percutaneous mitral balloon valvotomy and the new demographics of mitral stenosis. JAMA 1993;270:1731–6.
2.Prendergast B, Shaw T, Iung B, Vahanian A, Northridge DB. Contemporary criteria for the selection of patients for percutaneous balloon mitral valvuloplasty. Heart 2002;87(5):401–4.
3.Iung B, Cormier B, Ducimetiére P, Porte JM, Nallet O, Michel PL, et al. Functional results 5 years after successful percutaneous mitral commissurotomy in a series of 528 patients and analysis of predictive factors. J Am Coll Cardiol 1996;27:407–14.
4.Palacios IF, Tuczu ME, Weyman AE, Newell JB, Block PC. Clinical follow-up of patients undergoing percutaneous mitral balloon valvotomy. Circulation 1995;91:671–6.

20.Harken DE, Black H, Taylor WJ, Thrower WB, Ellis LB. Reoperation for mitral stenosis. A discussion of postoperative deterioration and methods of improving initial and secondary operations. Circulation 1961;23:7–12.
21.Ellis LB, Singh JB, Morales DD, Harken DE. Fifteen- to twenty-year study of one thousand patients undergoing closed mitral valvuloplasty. Circulation 1973;48:357–64.
22.John S, Bashi VV, Jairaj PS, Muralidharan S, Ravikumar E, Rajarajeswari T, et al. Closed mitral valvotomy: early results and long-term follow-up of 3724 consecutive patients. Circulation 1983;68:891–6.
23.Seltzer A, Cohn KE. Natural history of mitral stenosis: a review. Circulation 1972;45:878–90.
24.Iung B, Cormier B, Ducimetie`re P, Porte JM, Garbarz E, Michel PL, et al. Re´sultats a` 5 ans de la commissurotomie mitrale percutane´e a` partir d’une se´rie de 606 patients. Arch Mal Coeur 1996;89:1591–8.
25.Herrmann HC, Ramaswamy K, Isner JM, Feldman TE, Carroll JD, Pichard AD, et al. Factors influencing immediate results, complications and short-term follow-up status after Inoue balloon mitral valvotomy: a North American multicenter study. Am Heart . 1992;124:160–6.
26.Desideri A, Vanderperren O, Serra A, Barraud P, Petitclerc R, Lespérance J, et al. Long term (9 to 33 months) echocardiographic follow-up after successful percutaneous mitral commissurotomy. Am J Cardiol 1992;69:1602–6.
27. Vahanian A, Michel PL, Cormier B, Vitoux B, Michel X, Slama M, et al. Results of percutaneous mitral commissurotomy in 200 patients. Am J Cardiol 1989;63:847–52.
28.Palacios IF, Block PC, Wilkins GT, Weyman AE. Follow-up of patients undergoing percutaneous mitral balloon valvotomy. Circulation 1989;79:573–9.
29.Dean LS, Mickel M, Bonan R, Holmes DR Jr, O'Neill WW, Palacios IF, et al. Four-year follow-up of patients undergoing percutaneous balloon mitral commissurotomy. A report from the NHLBI balloon valvuloplasty registry. J Am Coll Cardiol 1996;28:1452–7.
30.Pathan AZ, Mahdi NA, Leon MN, Lopez-Cuellar J, Simosa H, Block PC, et al. Is redo percutaneous mitral balloon valvuloplasty (PMV) indicated in patients with post-PMV mitral restenosis? J Am Coll Cardiol 1999;34(1):49-54.
31.Cohen DJ, Kuntz RE, Gordon SP, Piana RN, Safian RD, McKay RG, et al. Predictors of long-term outcome after percutaneous balloon mitral valvuloplasty. N Engl J Med 1992;327:1329–35.
32.Post JR, Feldman T, Isner J, Herrmann HC. Inoue balloon mitral valvotomy in patients with severe valvular and subvalvular deformity. J Am Coll Cardiol 1995;25(5):1129-36.
33.Sutaria N, Shaw TR, Prendergast B, Northridge D. Transoesophageal echocardiographic assessment of mitral valve commissural morphology predicts outcome after balloon mitral valvotomy. Heart 2006;92(1):52-7.
34.Bezdah L, Drissa MA, Kasri R, Baccar H, Belhani A. Echocardiographic factors determining immediate result of percutaneous mitral balloon commissurotomy. Tunis Med 2007:85(6):479-84.
35.Rifaie O, Esmat I, Abdel-Rahman M, Nammas W. Can a novel echocardiographic score better predict outcome after percutaneous balloon mitral valvuloplasty? Echocardiography 2009;26(2):119-27.