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Original article
Prevalence of significant tricuspid regurgitation in patients with successful percutaneous mitral valvuloplasty for mitral stenosis: results from 12 years' follow-up of one centre prospective registry
  1. Seung-Pyo Lee1,2,
  2. Hyung-Kwan Kim1,2,
  3. Kyung-Hee Kim1,2,
  4. Ji-Hyun Kim1,
  5. Hyo Eun Park2,3,
  6. Yong-Jin Kim1,2,
  7. Goo-Yeong Cho2,4,
  8. Dae-Won Sohn1,2
  1. 1Cardiovascular Center, Seoul National University Hospital, Seoul, Korea
  2. 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  3. 3Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Korea
  4. 4Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea
  1. Correspondence to Professor Hyung-Kwan Kim, Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, 101 Daehak-ro, Jongro-gu, Seoul 110-744, Korea; hkkim73{at}


Background Percutaneous mitral valvuloplasty (PMV) is an attractive therapeutic option for mitral stenosis (MS).

Objective To investigate the incidence and development of tricuspid regurgitation (TR) long after successful PMV.

Design, patients and interventions A prospective cohort of 299 patients with symptomatic MS who underwent successful PMV as first-line treatment between 1988 and 2010.

Setting One tertiary university hospital.

Main outcome measures Significant TR, defined as a grade ≥3 on echocardiographic analysis.

Results Although most TR regressed in these patients immediately after the procedure, 56 patients developed significant TR during follow-up (median 12 years, IQR 8.0–18.0 years). The cumulative incidence of significant TR increased time-dependently (9.4%, 19.8% and 35.2% at 8, 12 and 18 years of follow-up, respectively). Atrial fibrillation (AF) and TR grade ≥2 before PMV were found to be independent predictors of significant TR (HR (95% CI) 3.049 (1.169 to 7.949) and 3.016 (1.303 to 6.982), p=0.023 and 0.010 for pre-PMV AF and pre-PMV TR grade ≥2, respectively). Even after, exclusion of patients with significant TR at baseline, pre-PMV TR grade ≥2 and AF remained important factors of de novo TR development. Mitral valve restenosis was also associated with late significant TR development.

Conclusions Significant TR after successful PMV in patients with MS is not uncommon long after PMV. TR development is closely associated with mitral valve restenosis. More attention should be paid during long-term follow-up to TR development in patients with MS who have significant pre-PMV TR and/or AF.

  • Atrial fibrillation
  • mitral stenosis
  • percutaneous procedures
  • tricuspid regurgitation
  • valvuloplasty
  • heart failure
  • cardiac function
  • imaging and diagnostics
  • echocardiography
  • valvular disease
  • MRI
  • arrhythmias
  • diastolic dysfunction
  • tricuspid valve disease
  • echocardiography-exercise
  • stress testing
  • cardiac imaging
  • valvular heart disease

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Despite a steady decrease in its incidence, rheumatic mitral stenosis (MS) still accounts for a substantial proportion of valvular heart disease in developing countries.1 MS typically induces a pressure overload in the left atrium (LA) over time, which leads to progressive atrial dilatation and finally, to the creation of a profibrillatory environment in the LA that manifests clinically as atrial fibrillation (AF).

Of the available treatments for MS, percutaneous mitral valvuloplasty (PMV) is less invasive than open surgery of the mitral valve (MV).2 Guidelines recommend PMV as the first therapeutic option for haemodynamically significant MS when MV morphology favours PMV.3 Successful PMV is known to reverse, in the short term, the haemodynamic threats of pulmonary hypertension,4–6 tricuspid regurgitation (TR)7 ,8 and LA remodelling9 posed by MS.

Patients with MS requiring PMV often have a degree of concomitant TR.10 ,11 More than one-third of patients with MS have been reported to have at least moderate TR.12 More importantly, marked TR before PMV is a significant predictor of outcome after PMV.13 AF, a common arrhythmia in patients with MS,14–18 is well known to predispose a patient to the development and progression of TR in patients with MV disease, which in turn impairs their quality of life and reduces survival.7 ,14 ,17 ,18 Although the impact on clinical outcome of significant TR before PMV is well known,9 ,19 the effect of de novo significant TR development or the redevelopment of TR in the long term after PMV is not. It is known that TR may develop in the long term in patients who have undergone successful left-sided valve surgery,17 ,20 and possibly, a similar phenomenon might occur long after successful PMV. In addition, a failure to correct associated TR after PMV raises concerns about TR progression over time. If this occurred, the long-term ‘sequelae’ of PMV might reduce the beneficial haemodynamic effects of PMV. The impact of progressive TR development after PMV on the long-term outcome has not been comprehensively investigated.

Accordingly, we analysed a prospective cohort of 299 patients with MS who had undergone successful PMV in order to document the incidence of significant TR long after successful PMV. The median follow-up period in this cohort is 12 years, which is the minimal time required to observe a long-term outcome such as TR (re)development, given that significant TR development after left-sided valve intervention was clinically evident only after 10 years of follow-up.20

Subjects and methods

Study subjects

The Seoul National University Hospital PMV registry was started in 1988 and prospectively enrolled patients with moderate or severe symptomatic MS undergoing PMV.9 Standard case report forms containing baseline clinical, anthropometric, echocardiographic and cardiac catheterisation data were obtained from all patients at baseline and during follow-up. Between April 1988 and December 2010, 397 patients underwent PMV as a first-line treatment for symptomatic MS, and were initially screened as candidates for this study. Patients with unsuccessful PMV results, defined as an immediate post-PMV mitral valve area (MVA) of <1.5 cm2 (n=40) or a mitral regurgitation grade of ≥3 (n=17), and those without follow-up data for any 12-month period after successful PMV (n=41) were excluded. Consequently, 299 patients constituted the study cohort (figure 1). The study protocol was approved by the institutional review board of our hospital. Baseline laboratory tests, anthropometric measures and medical history were systematically recorded during echocardiographic examinations.

Figure 1

Cohort selection flowchart of the 397 patients enrolled in the percutaneous mitral valvuloplasty database; 299 patients were included in the final analysis. F/U, follow-up; MR, mitral regurgitation; MVA, mitral valve area; PMV, percutaneous mitral valvuloplasty.

Echocardiographic examination

Comprehensive two-dimensional (2D) and Doppler echocardiographic examinations were performed in all patients <2 weeks before and 3 days after PMV with a commercially available echocardiography machine.

Left ventricular (LV) end-systolic/diastolic dimensions, LV end-diastolic wall thicknesses and LV ejection fractions were measured using standard M-mode tracings in parasternal short-axis view at the papillary muscle level. The echo score of the MV was calculated by adding up the grade of the leaflet thickening, mobility, calcification and subvalvular thickening, each on a scale from 1 to 4, as previously described.21

Mitral regurgitation and TR were assessed based on colour flow imaging findings, according to previous reports,14 ,20 using the following grading system: 0, none; 1, trivial; 2, mild; 3, moderate and 4, severe; grades were agreed by at least two expert echocardiography specialists.

Maximal LA volume was measured during end-systole using the prolate ellipsoid method and calculated as follows: LA volume= 0.523×D1×D2×D3, where D1 denotes the anteroposterior LA dimension measured at the standard parasternal long-axis view; D2 is the superoinferior LA dimension at the apical four-chamber view; and D3 is the LA width (minor axis) perpendicular to D2 from the apical four-chamber view.22

Pulmonary artery systolic pressure was calculated from the TR jet velocity after ensuring that no significant pressure gradient across the right ventricular outflow tract was present.

MVA was assessed using two-dimensional planimetry and the pressure half-time method. 2D planimetry was used because MVA on 2D planimetry has been proved to be closely correlated with anatomical MVA,.23 With the exception of immediate post-procedural MVA, the pressure half-time method was also used for comprehensive assessment of MVA. MVA is presented as the pre-procedural MVA, immediate post-procedural MVA and final MVA—that is, MVA at the final echocardiographic follow-up. An average of three measurements were made in patients with sinus rhythm and five measurements in patients with AF.

Cardiac catheterisation and PMV

Cardiac catheterisation was carried out by a standard technique using a Cournand catheter (USCI, Billerica, Massachusetts, USA). The PMV procedure was performed using a stepwise Inoue balloon technique with careful monitoring of the haemodynamic status. Mitral regurgitation grades were determined immediately after PMV with left ventriculography and graded according to the Sellers classification.24

Patient follow-up

A case report form that included information on the occurrence of significant valvular diseases requiring intervention, including restenosis of the treated MV and TR progression, was completed every 2–3 years at echocardiographic follow-up and at clinical follow-up each year. Restenosis of the treated MV was defined as a final MVA <1.5 cm2. Special emphasis was given to the collection of data related to the primary study end point—namely, significant TR (re)development. Significant TR was defined as TR with a grade ≥3. Patients reaching the primary end point or patients undergoing re-PMV/valve replacement during follow-up were censored.

Statistical analysis

Continuous or dichotomous variables are presented as mean ± SD or percentages and compared using the Student t test or the χ2 test, respectively. The cumulative incidence of events was analysed with Kaplan–Meier survival curves. Variables found to be associated with outcome were initially analysed with univariate Cox regression analysis and then, variables with a p value <0.10 were incorporated into a multivariate Cox regression model with an entry method which identified factors significantly predictive of the predefined end point. To identify the optimal cut-off value for late TR development, a receiver operating characteristic curve analysis was used. The cut-off value was defined as one with maximal sum of the sensitivity and specificity. All analysis was carried out with SPSS V. 17.0 (SPSS Inc) and a two-tailed p value <0.05 was considered statistically significant.


Of the 299 patients, 56 (re)developed marked TR after successful PMV over a median follow-up of 12 years (IQR 8–18 years). Of these 56 patients, 43 patients developed moderate TR, and 13 patients severe TR. The incidence of significant TR increased linearly with time—that is, 9.4%, 19.8% and 35.2% for 8, 12, 18 years of follow-up, respectively (figure 2A).

Figure 2

Cumulative incidence of late significant tricuspid regurgitation (A) in the entire study population and according to (B) pre-PMV rhythm status and (C) pre-PMV TR ≥ grade 3 or (D) pre-PMV TR ≥ grade 2. Significant TR was defined as a TR grade of ≥ 3. p Value adjusted for other variables. PMV, percutaneous mitral valvuloplasty; TR, tricuspid regurgitation.

The clinical and echocardiographic characteristics of patients, according to the presence or absence of significant TR at follow-up, are summarised in table 1. When the cohort was dichotomised based on significant TR at final follow-up, those who (re)developed significant TR were found to be older, and to be more likely to have AF. Before index PMV procedures, patients who (re)developed significant TR tended to have more severe MS (as represented by a smaller MVA and a higher echo score), a larger LA volume and were more likely to have pre-PMV significant TR (TR grade ≥3) as well as mild TR (TR grade 2). Immediately after the PMV procedures, although MVA and mean LA pressure equalised in patients with or without late significant TR, post-PMV pulmonary artery systolic pressure and LA volume remained greater in patients with late significant TR (table 1). Moreover, TR regressed markedly immediately after the procedure in a substantial majority of patients with pre-PMV significant TR, with only five patients having significant TR <6 months after PMV.

Table 1

Baseline clinical, pre- and post-PMV haemodynamic characteristics of the study participants

The results of Cox regression analysis for TR (re)development are summarised in table 2. Cox regression analysis showed that pre-PMV TR ≥ grade 3 and initial rhythm status significantly predicted late significant TR (re)development after successful PMV (table 2). Late significant TR was found to be 4.60 times more likely to develop in patients with pre-PMV AF than in patients with pre-PMV sinus rhythm (HR=4.601, 95% CI 1.689 to 12.537, adjusted p=0.003) (figure 2B). Also, patients with pre-PMV TR ≥ grade 3 were found to be 4.38 times more likely to (re)develop significant TR than those with a pre-PMV TR grade of <3 (HR=4.384, 95% CI 1.560 to 12.322, adjusted p=0.005) (figure 2C). Interestingly, pre-PMV TR ≥ grade 2 was a significant risk factor for (re)development of significant TR (HR=3.016, 95% CI 1.303 to 6.982, adjusted p=0.010) (figure 2D).

Table 2

Cox regression analysis of predicting significant TR after successful PMV in the entire population

To dissect the incidence and risk factors of de novo significant TR development, we analysed the population after excluding patients with significant TR before PMV (table 3). The incidence of significant TR increased linearly with time—that is, 7.9%, 16.5% and 31.7% for 8, 12, 18 years of follow-up, respectively (figure 3A). Again, pre-PMV AF was an important predictor of de novo TR development (HR=2.655, 95% CI 1.002 to 8.178, adjusted p=0.043) (figure 2B), as was pre-PMV TR grade 2 (HR=2.601, 95% CI 1.019 to 6.639, adjusted p=0.046) (figure 2C).

Table 3

Cox regression analysis of predicting significant TR after successful PMV in patients with pre-PMV TR < grade 3

Figure 3

Cumulative incidence of late significant TR tricuspid regurgitation in patients without pre-PMV significant TR (pre-PMV TR ≥3). Incidence of TR (A) in the entire population and according to (B) pre-PMV rhythm status and (C) pre-PMV TR grade 2. Significant TR was defined as TR grade of ≥3. p Value adjusted for other variables. PMV, percutaneous mitral valvuloplasty; TR, tricuspid regurgitation.

The effect of MV restenosis on TR (re)development was analysed by receiver operating characteristic curve analysis. The optimal final MVA value for predicting late significant TR was 1.55 cm2 (area under the curve 0.693, 95% CI 0.619 to 0.767, p<0.001, sensitivity 46.0%, specificity 87.0%). Based on this value, a significant proportion of patients with MV restenosis had late significant TR (27.8%, 42/151), as compared with those without (8.7%, 11/126) (p=0.012).


In this study, we examined the incidence and determinants of significant TR (re)development after successful PMV. It was found that a substantial proportion of patients with MS (re)developed TR in a time-dependent manner even after successful PMV. On multivariate analyses, pre-PMV AF, significant TR pre-PMV and MVA at final follow-up—that is, MV restenosis, were found to be the three factors predicting significant TR (re)development long after successful PMV. Since progressive decline of MVA over time has been well documented even after successful PMV,11 ,15 ,16 and there are no medical interventions to slow the progression of MV restenosis, the MVA achieved immediately after PMV may be of value in preventing late TR (re)development.

As proved by several earlier reports, including ours, significant TR is not rare even after successful surgical repair of left-sided valve lesions.13 ,14 ,20 The presence of AF has been consistently identified as a significant predictor of late TR development,14 ,17 ,20 and patients who underwent a concomitant successful Maze operation during their left-sided valve surgery have been reported to have significantly less TR during follow-up.14 In this study, a close link was also found between late TR (re)development and AF, which is not altogether surprising, when one considers that MS is a disease frequently associated with AF. Although the mechanism of TR progression in AF is still unknown, it is generally accepted that AF induces mechanical and electrical remodelling of the right atrium, leading to tricuspid annular dilatation that results in significant TR development.25 ,26 TR itself in turn leads to right ventricular dilatation and dysfunction, further tricuspid valve (TV) annular dilatation and papillary muscle displacement,27 all of which may worsen TR.25

Previous studies have focused only on mid-term outcomes of pre-PMV TR after successful PMV,7 ,8 ,13 ,19 and the results obtained were mixed. For example, some earlier studies concluded that TR regresses after successful PMV,7 ,8 which is partially supported by our data also, whereas others reported that this is not always the case.13 ,18–20 These contradictory results may be attributable to small cohort sizes or, more importantly, to limited duration of follow-up after PMV. In addition, previous reports investigated only changes in TR immediately after PMV or for up to 3 years, which does not take into account the possible development of TR late after successful intervention on diseased left-sided valves. TR appears to clinically manifest after more than 10 years after left-sided valve intervention.20 Thus, long-term echocardiographic and clinical observations are indispensable for reaching more definite conclusions about TR progression after successful PMV.

This study is the first to examine long-term follow-up results (median 12 years), mainly focusing on late TR after successful PMV. Once significant late TR develops, quality of life and prognosis of patients worsen,28–30 even in the absence of LV dysfunction or pulmonary hypertension. Management of such patients is challenging because advanced right ventricular dysfunction frequently coexists. Hence, the best option available is the prevention or detection of significant TR at an earlier stage, and for this, an understanding of the determinants of late TR is essential.

In addition to the presence of pre-PMV AF, significant TR before PMV was also found to be an independent predictor of late TR (re)development after successful PMV, even though in most patients significant regression of TR occurred immediately after PMV. Given the high incidence of AF in patients with MS and its close relationship to TR, it is not unexpected that significant TR before PMV is associated with late TR (re)development. However, multivariate Cox proportional analysis showed its ‘independent’ association with late TR (re)development. Although the mechanisms involved are not clear, we presume that TV annular dilatation plays a role.27 TV annular dilatation, often seen in patients with significant TR before PMV,18 ,25 ,26 is considered the most important contributor to the development of late TR.12 ,13 ,17 Although successful PMV can significantly reduce TR severity, it cannot correct pre-existing tricuspid annular dilatation, unlike MV replacement combined with TV repair, for which promising results were obtained in some small studies treating tricuspid annular dilatation and associated TR.31 Thus, a continuous subclinical interaction between AF and tricuspid annular dilatation after successful PMV could cause TR to progress gradually with time. Even after excluding those patients with significant pre-PMV TR, AF was a significant predictor of late TR development, demonstrating this long-term, continuous interaction between TR development and AF. Taken together, patients with pre-PMV AF and significant TR should be regarded as an important patient subset, to which we should pay more attention and provide earlier intervention.

Another important finding of our study is that patients who developed restenosis of the treated MV were more likely to (re)develop significant TR in the long term, highlighting a pivotal link between MS (re)development and the occurrence of late TR. The gradual but progressive increase in the haemodynamic burden induced by MV restenosis may lead to atrial enlargement with concomitant tricuspid annular dilatation and AF, all of which are generally accepted as the most important substrates of TR (re)development. Thus, the prevention of MV restenosis is an important therapeutic strategy to prevent late TR (re)development. Since no medical treatments have been proved to halt or slow the progression of MS, and MV restenosis after PMV is well known to be progressive,11 ,15 ,16 the best approach should be to secure as large an MVA as possible immediately after PMV, as suggested by Song and his colleagues.11 Avoiding PMV in patients with MS associated with significant TR, in particular when there is a marked enlargement of the tricuspid annulus, may be another option.

Despite the prospective nature of this study, it has several limitations. First, it cannot provide definite recommendations as to whether earlier intervention has long-term benefit in patients with MS—that is, it is unclear whether PMV before the development of AF or significant TR leads to better TV-related outcomes. Nevertheless, patients with multiple predictors of TR (re)development are an important patient subset, which merit increased attention. In addition, given the impact of AF on systemic thromboembolism, surgical treatment together with the Maze procedure may be a preferred treatment in some patient subsets.32 Second, this study does not provide guidance as to whether the surgical treatment of MS is a better option than PMV in patients with pre-PMV AF or significant TR. Although PMV carries a lower risk than MV surgery, with or without concomitantly performed TV surgery like tricuspid annuloplasty/TV replacement, the invasiveness of the operation cannot be overlooked. Third, TR is more sensitive to loading conditions than mitral regurgitation. Information on the tricuspid annular diameter might be helpful, but we do not have these data. Fourth, this study does not show that the (re)development of TR after successful PMV leads to a worse outcome. However, in a preliminary analysis of our patients, late TR (re)development after successful PMV was associated with a significant increase in TV-related procedures (data not shown); this needs to be confirmed in the near future.

In conclusion, the (re)development of late significant TR, even after successful PMV in patients with significant symptomatic MS is not uncommon, with an estimated incidence of 35.2% at a median of 12 years after PMV. The prevalence of significant TR after successful PMV was found to increase in a time-dependent fashion. This study identifies pre-PMV AF and significant TR before PMV as independent predictors for late TR (re)development. Our study also emphasises a close relationship between MV restenosis and late TR (re)development. Therefore, we recommend that more attention should be paid during follow-up to patients with symptomatic MS with pre-PMV AF and/or significant TR.

Key messages

  • We here provide unique, long-term data of a cohort of about 300 patients for whom percutaneous mitral valvuloplasty (PMV) was successful. The median follow-up in our cohort is 12 years. Such long-term data are important for patients with significant mitral stenosis because a substantial proportion of patients are in their third or fourth decade when undergoing PMV. These patients may survive for more than 20 years.

  • We found that significant TR (re)developed in a time-dependent manner even after successful PMV. This is in contrast to some previous reports which showed a mid-term beneficial effect of successful PMV on tricuspid regurgitation (TR).

  • Atrial fibrillation and a TR grade ≥3 before PMV procedure were important predictors of late TR (re)development after successful PMV.

  • Although not proved in our study, we provide a theoretical basis for the possible benefits of an early intervention for patients before atrial fibrillation or significant TR are established.


The authors thank Ok-Yi Park, a sonographer in the echocardiography laboratory for her helpful assistance in gathering the complete data.


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  • Funding This research was partly supported by the leading foreign research institute recruitment programme through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) (0640-20100001).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the institutional review board of Seoul National University Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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