Progression or persistence of tricuspid regurgitation after mitral valve replacement in patients with pre-operative moderate tricuspid regurgitation

Abstract

Purpose

There is a paucity of data on factors contributing to post-operative tricuspid regurgitation among patients with pre-operative moderate functional tricuspid regurgitation undergoing mitral valve replacement for rheumatic heart disease, the most common cause of mitral valve disease in the developing world.

Methods

Between January 2013 and December 2018, 476 patients underwent mitral valve replacement in our institution, of which 135 fulfilled the exclusion criteria. Of the remaining 341 patients, 142 had moderate functional tricuspid regurgitation. Our primary objective was to estimate the number of patients with of post-operative moderate to severe tricuspid regurgitation. Secondary outcomes were to determine the factors associated with it.

Results

Among the 142 patients who had pre-operative moderate functional tricuspid regurgitation (TR), mitral stenosis (46.4%) was the predominant lesion. Concomitant tricuspid annuloplasty (TAP) was done in 41 patients (28.9%). The median duration of follow-up was 35 (11, 79.5) months. Post-operative moderate to severe TR was recorded in 41.5%. Atrial fibrillation was significantly associated with post-operative moderate to severe TR (p = 0.006). Among the patients who did not undergo TAP, post-operative moderate to severe TR (85%, 50/59) compared to post-operative mild TR (61%, 51/83) with a p-value of 0.003.

Conclusion

Our data show that concomitant tricuspid annuloplasty during mitral valve replacement can be considered even in patients with pre-operative moderate TR and that pre-operative atrial fibrillation is significantly associated with post-operative TR.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s12055-025-01965-0.

Introduction

Functional tricuspid regurgitation (TR) is a complex valvular lesion where the tricuspid valve (TV) leaks during systole in the absence of an organic pathology of leaflets. As our understanding of this disease has evolved, there has been a paradigm shift in the approach to functional TR. Functional TR is no longer considered a benign and self-resolving condition, as its impact on survival is well documented in the literature [1]. Consequently, concomitant tricuspid annuloplasty (TAP) is recommended for severe TR. However, managing moderate TR remains a topic of debate. Most of the literature on TR focuses on degenerative heart disease, while rheumatic heart disease (RHD) remains the leading cause of mitral valve disease in our country, where 13.2 million people were affected by it, accounting for about 40% of the disease burden in the world [2]. Although there is a marked decline in the overall disease burden in low and middle-income countries (LMICs) such as North Africa and China (71%), the decline in India is only 18%, making India the rheumatic capital of the world [2]. Further, the factors associated with the progression or regression of moderate TR in our population are lacking. Therefore, this study was conducted to assess the progression or persistence of pre-operative moderate functional TR and identify the factors associated with it after mitral valve replacement among patients with pre-operative moderate TR.

Methodology

Study design

This was a retrospective study, for which approval from the Institutional Review Board (IRB No.13609 dated 25.11.2020) and waiver of consent were obtained. Between January 2013 and December 2018, 476 patients underwent mitral valve replacement in our institution. Of these, 135 patients were excluded as they had one of the limiting criteria (Fig. 1). Of the remaining 341 patients, those with pre-operative mild and severe TR were excluded, and 142 with moderate functional TR were included in the study. The primary outcome of interest was identifying the number of patients with post-operative moderate to severe TR. The secondary outcome was to identify the factors associated with the same. Demographic, clinical data and peri-operative data were obtained from the hospital’s electronic database.

Fig. 1.

Patient flow chart. TR, tricuspid regurgitation

Echocardiogram

The echocardiogram was performed by a certified echocardiography technician and verified by a cardiologist. It was done using a Philips iE 33 ultrasound imaging system (©Koninklijke Philips N.V.) A two-dimensional Echocardiogram and colour-flow Doppler done within 3 months pre-operatively was taken as a ‘pre-operative’ study. All patients had an echocardiogram done at discharge. Since the frequency and the intervals between echocardiograms in the post-operative period were non-specific, the echocardiogram done at the last follow-up was considered for assessment. The degree of TR was evaluated using the flow convergence method and graded as mild, moderate or severe when the radius of Proximal Isovelocity Surface Area (PISA) at mid-systole was ≤ 5 mm, 6–9 mm and > 9 mm, respectively [3]. A decrease by one grade was considered regression and an increase by one grade was considered progression. The tricuspid annulus diameter was measured at the end-diastole in the apical four-chamber view. Pulmonary artery systolic pressure (PASP) was estimated from the maximum TR jet velocity and right atrial pressure. Pulmonary artery hypertension (PAH) was defined as a PASP of more than 40 mmHg. The left ventricular ejection fraction was measured using Simpson’s biplane method. The right ventricular (RV) dysfunction was defined by a tricuspid annular plane systolic excursion (TAPSE) of less than 17 mm. The right ventricular coupling is a ratio of TAPSE to PASP. The RV is considered uncoupled if the ratio is less than 0.31. If the left atrium (LA) is more than 6 mm, it is considered enlarged.

Surgical procedure

All 142 patients underwent mitral valve replacement with mechanical or bioprosthetic prosthesis via conventional median sternotomy under cardiopulmonary bypass, with aortic and bi-caval cannulation. Antegrade cold blood cardioplegia was administered for myocardial protection. All patients with a tricuspid annulus of over 40 mm underwent concomitant tricuspid ring annuloplasty. However, in patients with an annulus of 40 mm or less, TAP was performed only in those with significant regurgitation in saline testing.

Statistical plan

The sample size for this study was calculated based on an expected prevalence of post-operative moderate to severe TR of 14.4% [4], with a precision of 6% and a 95% confidence level. Using the standard formula for proportions, the required sample size was estimated to be 132 patients. The study included 142 patients, which ensured sufficient precision for estimating the prevalence of moderate to severe TR. Baseline characteristics and clinical events were presented as frequencies, with proportions for categorical variables. Pearson’s chi-square test or Fisher’s exact test was applied to categorical variables. Continuous variables were presented as mean with standard deviations or median with interquartile ranges (IQRs), and statistical comparisons were done using the independent t-test and Mann–Whitney U test. A p-value of less than 0.05 was considered significant. The statistical package SPSS 21.0. was used for statistical analysis.

Results

The mean age of the 142 patients included in this study was 44 ± 12.05 years, of which 93(65%) were female patients (Table 1). All 142 patients had rheumatic heart disease with severe mitral stenosis in 66 (46.4%), mitral regurgitation in 28 (19.7%) and mixed lesions in 48 (33.8%) patients. The mean left ventricular ejection fraction was 55.9 ± 4%. RV dysfunction was seen in 62 (43.7%) patients. Pulmonary artery hypertension was noted in 120 (85%), and the LA was enlarged in 75 (52.8%) patients. Atrial fibrillation was recorded in 103 patients (72.5%). The median duration of symptoms was 12 months (IQR 6–48), and majority of the patients had New York Heart Association (NYHA) class II symptoms (Table 1).

Table 1.

Baseline characteristics

Age (mean ± SD)	44.19 ± 12.05
Female	93 (65.5%)
Duration of symptoms in months (median, IQR)	12 (6–48)
NYHA (%)
1	1(0.7%)
2	111(78.2%)
3	28(19.7%)
4	2(1.4%)
Atrial fibrillation	103(72.5%)
LA size (%)
More than 6 mm	32 (22.5%)
Predominant mitral lesion (%)
Mitral stenosis	66 (46.4%)
LVEF (mean ± SD)	55.95 ± 4.55
Right ventricular dysfunction
TAPSE < 17 mm	62 (43.7%)
Pulmonary artery hypertension
> 40 mmHg	120 (84.5%)
RV-PA uncoupling
TAPSE/PASP < 0.31	64 (45.1%)
Tricuspid annulus size (%)
More than 40 mm	33 (23.2%)
TAP
Done	41 (28.9%)
Not done	101 (71.1)

NYHA New York Heart Association, LA left atrium, LVEF left ventricular ejection fraction, TAPSE tricuspid annular plane systolic excursion, TAP tricuspid annuloplasty, RV right ventricle, PA pulmonary artery, PASP pulmonary artery systolic pressure

The tricuspid annulus size was more than 40 mm in 33 (23.2%) patients. Concomitant TAP was done in 41 patients (28.9%). All 41 patients underwent ring stabilisation of the annulus with either rigid or three-dimensional rings (3D). The rings used were the Contour 3D (Medtronic®, Minneapolis, MN)—18 (sizes 26, 28, 30, 32); MC3 (Edwards Lifesciences® LLC, Irvine, CA)—21 (sizes 28, 30); and Carpentier-Edwards ring (Edwards Lifesciences® LLC, Irvine, CA)—2 (sizes 28, 30).

The median duration of follow-up was 35 (11, 79.5) months. Post-operative moderate to severe TR was recorded in 41.5% (59/142). Among the 41.5% (59/142) patients, 30% (18/59) had progression of TR, 40% (24/59) had transient regression to mild TR at discharge with subsequent progression to moderate or severe TR (moderate 20/24; severe 4/24) and 28% (17/59) had persistence of moderate TR (Fig. 2). Factors associated with post-operative moderate to severe TR in our cohort are depicted in Table 2.

Fig. 2.

Fate of moderate to severe TR. TR, tricuspid regurgitation

Table 2.

Factors associated with post-operative moderate to severe TR after mitral valve replacement

Variables	Moderate to severe TR (n = 59)	Mild TR (n = 83)	P-value
Age (mean ± SD)	46.34 ± 12.06	42.66 ± 11.89	0.073
Gender (%)
Male	20 (33.9)	29 (34.9)	0.898
Female	39 (66.1)	54 (65.1)
Duration of symptoms in months (median, IQR)	24 (12–48)	12 (6–48)	0.064
NYHA (%)
1	0	1 (1.2)	0.864
2	48 (81.4)	63 (75.9)
3	10 (16.9)	18 (21.7)
4	1 (1.7)	1 (1.2)
ECG (%)
Sinus rhythm	9 (15.3)	30 (36.1)	0.006
Atrial fibrillation	50 (84.7)	53 (63.9)
LA size (%)
≤ 6 mm	46 (78)	64 (77.1)	0.904
> 6 mm	13 (22)	19 (22.90)
Mitral lesion (%)
Mitral stenosis	33 (55.9)	33 (39.8)	0.160
Mitral regurgitation	10 (16.9)	18 (21.7)
Mixed lesion	16 (27.1)	32 (38.6)
LVEF
≤ 50%	4 (6.8)	4 (4.8)	0.719
> 50%	55 (93.2)	79 (95.2)
TAP (%)
Done	9 (15.3)	32 (38.6)	0.003
Not done	50 (84.7)	51 (61.4)
TAPSE (%)
≥ 17 mm	29 (49.2)	51 (61.4)	0.146
< 17 mm	30 (50.8)	32 (38.6)
Pulmonary artery systolic pressure (%)
≤ 40 mmHg	12 (20.3)	10 (12)	0.178
> 40 mmHg	47 (79.7)	73 (88)
Tricuspid annulus size (TAP not done) (n = 101) (%)
< 35 mm	37 (74)	39 (76.5)	0.774
≥ 35 mm	13 (26)	12 (23.5)
RV-PA coupling (%)
< 0.31	25 (42.4)	39 (47)	0.586
≥ 0.31	34 (57.6)	44 (53)

TR tricuspid regurgitation, NYHA New York Heart Association, ECG electrocardiogram, LA left atrium, LVEF left ventricular ejection fraction, TAP tricuspid annuloplasty, TAPSE tricuspid annular plane systolic excursion, RV-PA coupling right ventricle/pulmonary artery coupling

At the last follow-up in our cohort, post-operative pulmonary artery hypertension was noted in 44% (26/59) in the moderate to severe TR group and 6% (5/83) in the mild TR group (p < 0.001). Post-operative right ventricle-pulmonary artery (RV-PA) uncoupling was seen in 37% (22/59) in the moderate to severe TR group as opposed to 4.8% (4/83) in the mild TR group (p < 0.001).

Discussion

In this study, post-operative moderate to severe TR was 41.5% (59/142) as opposed to 3.3 to 5% reported in studies analysing degenerative mitral valve disease [5, 6]. Our findings are consistent with the literature, in which RHD was noted to have a higher prevalence of moderate to severe TR in the postoperative period [4]. In our study, mitral stenosis was the predominant lesion as compared to mitral regurgitation in degenerative mitral disease. Our study found no correlation between mitral stenosis and post-operative moderate to severe TR; the literature on this is sparse.

Functional TR is a spectrum, and the current understanding of the disease is quite clear at the extremes. However, ambiguity persists in the moderate category, owing to its potential to worsen or regress following left-sided valve surgery. The trigger in left-sided heart disease is the elevation of the left atrial pressure (LAP), which results in a progressive dilation of the LA. In our study, 22.5% of patients had dilated LA, which, contrary to the literature [7], did not have any significant association with post-operative moderate to severe TR.

Pulmonary arterial hypertension occurs as the elevated left atrial pressure is transmitted backwards, raising the pulmonary capillary wedge pressure [7]. This post-capillary pulmonary hypertension with normal transpulmonary gradient and pulmonary vascular resistance is a passive phenomenon, which is reversible after mitral valve surgery [8]. If the LAP is persistently elevated, the integrity of the alveolar-capillary complex is altered due to the deposition of collagen type IV, leading to a combined pre- and post-capillary pulmonary hypertension, which is irreversible [9]. Shiran et al. reported PAH as a predictor of post-operative TR [10]. However, in our study, pre-operative PAH did not correlate with post-operative TR, similar to the findings reported by Song et al.[5]. The lack of association could be explained by the expected fall in pulmonary artery pressure following mitral valve replacement.

In normal circulation, the RV ejects blood into a low-impedance and high-capacitance circulation, and its muscle fibres are peculiarly suited to adapt better for an increase in the pre-load rather than after-load. A sustained increase in pulmonary artery pressure causes negative remodelling of the RV, leading to compensatory hypertrophy. This leads to dysfunction characterised by chamber dilation and annular dilation, which accentuates this vicious cycle. RV dysfunction is associated with the severity of TR [11]. In this study, RV dysfunction was recorded in 43% of the patients in the pre-operative period, and it was not associated with post-operative moderate to severe TR. This could possibly be explained by the fact that the present study considered TAPSE as a measure of RV function as opposed to other quantitative methods such as fractional area change, which has a better correlation with the severity of TR [12].

Sustained pressure and volume overload and its effect on RV function are dynamic and expressed as RV-PA coupling. This has recently been proposed as an index of RV function as it overcomes load dependency in patients with TR [13]. Ideally, it is measured invasively based on the flow-volume loops, but echocardiographic measurement based on the TAPSE/PASP ratio correlates well with invasive studies [14]. In our study, the TAPSE/PASP ratio did not have a significant influence on post-operative moderate to severe TR (p = 0.586). Interestingly, in the post-operative study, patients with moderate to severe TR showed significant (p < 0.001) RV-PA uncoupling. This is likely due to the persistence of pulmonary artery hypertension, which was also significantly (p < 0.001) more common in the post-operative moderate to severe TR group.

Atrial fibrillation (AF) is recognised as an important risk factor for the development of functional TR in patients with left-sided valvular heart disease [15], with its prevalence ranging between 20 and 83% [16–18]. In our study, AF was significantly associated with post-operative moderate to severe TR (85%, 50/59) compared to post-operative mild TR (64%, 53/83), with a p-value of 0.006, consistent with the findings in the literature [19]. The understanding of the influence of chronic AF is evolving, and of late, it has been considered a separate entity in the pathophysiology of functional TR, termed atrial-TR. Chronic AF per se can result in tricuspid regurgitation with a unique pattern of tricuspid annular dilatation [20]. Traditionally, annular dilation is believed to be a culmination of negative remodelling of the right ventricle (Ventricular Functional-TR), secondary to pulmonary hypertension or left-sided valve disease [21], characterised by dilation of RV along with displacement of the papillary muscles with pronounced leaflet tethering. However, in atrial-TR, the pattern of annular dilatation and papillary muscle displacement is distinct, with atrial dilatation being predominant with less pronounced RV dilation and leaflet tethering [22–24]. Disruption of helical and rotational blood flow in the right atrium due to AF was thought to contribute to the progression of TR [25]. Also, in RHD, the rheumatic process can directly affect the annulus, thereby contributing to dilation [26]. Despite its proven association with the progression of functional TR, AF is not included in the American Heart Association and European Society of Cardiology guidelines. On the other hand, as per the Japanese guidelines, persistent AF, even in a mild TR, is a class IIb indication for a concomitant tricuspid valve repair [27].

As the disease progresses, the tricuspid annulus undergoes geometric deformation from an elliptical and non-planar ring to a circular and planar ring [28]. A tricuspid annulus diameter of more than 40 mm (more than or equal to 70 mm in a heart arrested in diastole) or indexed tricuspid annulus diameter of more than 21 mm/m² is considered significantly dilated [21, 29]. Dreyfus et al. proposed an intervention based on the tricuspid annulus dilatation and not regurgitation, as dilation of the annulus reflects the severity of the disease and is less dependent on preload, afterload and contractility, unlike tricuspid regurgitation [21]. However, a recent meta-analysis does not support this approach [30]. Also, the threshold for dilated annulus among patients with moderate TR has not yet been identified, and it is thought to be lower in patients with RHD. Shiran et al. proposed that a TV annulus diameter of ≥ 35 mm is significant, regardless of the severity of regurgitation [19]. On applying this criterion to our study, in the 101 patients who did not undergo tricuspid annuloplasty, there was no correlation with post-operative TR (p = 0.774).

A tricuspid valve dilation of more than 40 mm is a class II indication for concomitant tricuspid valve surgery [31, 32]. In our study, 41 (29%) patients underwent concomitant TAP, which is comparable to data from the Society of Thoracic Surgeons database, where intervention for moderate TR in patients undergoing left-sided valve surgery is 30.6% [33, 34]. Among the patients who did not undergo TAP, post-operative moderate to severe TR (85%, 50/59) was more frequently observed than post-operative mild TR (61%, 51/83), consistent with the literature on rheumatic mitral valve disease (p = 0.003) [4, 35].

Limitations

The major limitation of our study is its retrospective nature. There could be interobserver variability in the echocardiogram reports as it was not done by the same technician/cardiologist. The parameter used in our study to grade the severity of TR is semi-quantitative. Currently, in our clinical practice, we use quantitative parameters such as Effective Regurgitant Orifice Area and Regurgitant volume. However, these were not available during the period of our study. We did not record long-term follow-up, so it is difficult to comment on overall survival. The secondary objectives were exploratory, and a specific sample size calculation was not performed for them. While this may limit the generalisability or statistical power of some secondary analyses, the sample size derived from the primary objective was sufficient to give the expected effect sizes and population characteristics.

Conclusion

Our data show that concomitant tricuspid annuloplasty during mitral valve replacement can be considered even in patients with pre-operative moderate tricuspid regurgitation and that pre-operative atrial fibrillation is significantly associated with post-operative TR.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contribution

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Raj Kumar Joel. The first draft of the manuscript was written by Raj Kumar Joel. Mr. Nagaraj did the statistical analysis. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

None.

Data availability

Available at request.

Code availability

Not applicable.

Declarations

Informed consent

A waiver of consent was obtained from the institutional ethics committee.

Human and animal rights statement

Not applicable as no experimental new procedure was carried out and no animals were involved in this study.

Ethics approval

This study was approved by the Institution Review Board and Ethics Committee (IRB No.13609 dated 25.11.2020).

Conflict of interest

None.