Which Type of Secondary Tricuspid Regurgitation Accompanying Mitral Valve Disease Should Be Surgically Treated?

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1 Ann Thorac Cardiovasc Surg 2013; 19: Online January 31, 2013 doi: /atcs.oa Original Article Which Type of Secondary Tricuspid Regurgitation Accompanying Mitral Valve Disease Should Be Surgically Treated? Tsuneo Ariyoshi, MD, Kouji Hashizume, MD, Shinichirou Taniguchi, MD, Takashi Miura, MD, Seiji Matsukuma, MD, Shun Nakaji, MD, and Kiyoyuki Eishi, MD Purpose: The purpose of this study was to examine changes in severity of secondary tricuspid regurgitation (TR) accompanying mitral valve disease, and to identify factors predicting failure of improvement in TR after mitral valve surgery. Methods: We studied 99 patients who had TR of grade 2+ preoperatively, 47 with tricuspid annuloplasty (TAP Group) performed concurrently, and 52 with mitral surgery alone (ntap Group). Predictors of failure of improvement in TR in the ntap Group were analyzed. Results: The mean follow-up period was 4.6 ± 2.7 years. There was a significant difference between the TAP and ntap Groups in TR improvement (93.6% vs. 67.3% respectively, p <0.001) and in change of TR grade (-2.1 ± 1.0 vs ± 1.0 respectively, p <0.001). Univariate analysis in the ntap Group identified rheumatic etiology, atrial fibrillation, mitral stenosis (MS), and large left atrium prior to surgery as risk factors for failure of improvement. In multivariate analysis atrial fibrillation was identified as a predictor of failure of improvement (p = 0.004). Conclusion: Our results suggest that TAP should be performed concurrently with mitral valve surgery in patients with secondary TR of grade 2+, especially those having atrial fibrillation, even if TR is not severe. Keywords: regurgitation, tricuspid valve, secondary Introduction It has been considered that the tricuspid valve should be repaired concurrently with surgery for mitral valve disease in patients with severe tricuspid regurgitation (TR). 1,2) However when the grade of TR is not severe concurrent The Department of Cardiovascular Surgery, Nagasaki University School of Medicine, Nagasaki, Nagasaki, Japan Received: February 14, 2012; Accepted: June 25, 2012 Corresponding author: Tsuneo Ariyoshi, MD. The Department of Cardiovascular Surgery, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Nagasaki , Japan tariyosh@nagasaki-u.ac.jp 2013 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved. tricuspid surgery is not performed at the time of mitral valve surgery in some cases, since improvement in TR may result from a reduction in right ventricular pressure and volume load. 3,4) However, it has been reported that TR may worsen in the late phase after surgery in some patients. 5,6) Factors associated with worsening of TR during the late phase after mitral valve surgery have not been fully characterized. The purpose of the present study was to retrospectively analyze the change in the severity of TR in the late phase after mitral valve surgery in patients with TR of grade 2+ or greater at the time of mitral valve surgery, and to identify the preoperative predictors of failure of improvement in TR after the surgery. Our intention was to elucidate which types of secondary TR accompanying mitral valve disease should be treated surgically at the time of mitral surgery. 428 Ann Thorac Cardiovasc Surg Vol. 19, No. 6 (2013)

2 Which Type of Secondary Tricuspid Regurgitation Accompanying Mitral Valve Disease Should Be Surgically Treated? Table 1 Preoperative and operative patient characteristics (n = 99) Age (range) 65.4 ± 10.4 (23 83) Gender Male Female Mean ± SD No. of patients (%) 38 (38.4) 61 (61.6) Rheumatic etiology 44 (44.4) Atrial fibrillation 72 (72.7) NYHA Class III 64 (64.6) Mitral stenosis 41 (41.4) Previous aortic or mitral surgery 18 (18.2) Left atrial dimension (mm) >60 mm 54.6 ± (34.3) LVEF(%) <50% 66.5 ± (11.1) Systolic PAP (mmhg) >40 mmhg 41.7 ± (47.5) Diabetes mellitus 12 (12.1) Renal dysfunction 6 ( 6.1) Previous mitral valve repair 45 (45.5) LVEF: left ventricular ejection fraction; PAP: pulmonary artery pressure Patients and Methods A total of 238 patients with mitral valve disease underwent mitral valve replacement (MVR) or mitral valvuloplasty at our institution between January 2001 and September 2010, including 99 with TR grade 2+ preoperatively. Severity of TR was classified from 1+ to 4+ according to the results of echocardiographic evaluation using the classification method previously reported. 7) Patients who had been diagnosed with congenital heart disease, dilated cardiomyopathy (DCM), ischemic heart disease, or infectious endocarditis before the surgery were excluded from the study. In addition, patients with postoperative recurrence of mitral regurgitation (MR) and those who were diagnosed with newonset aortic valve disease or coronary artery disease were excluded. All subjects underwent echocardiographic studies and cardiac catheterization before surgery. Patient characteristics and hemodynamic parameters prior to surgery are summarized in Table 1. A rheumatic etiology was diagnosed in 44 patients, and mitral stenosis (MS) was present in 41 patients. MVR was performed in 54 patients, with use of a bioprosthetic valve in patients age 70 or older. The decision to perform concomitant tricuspid valve repair in patients with TR grade 2+ was based on the surgeon s inspection during surgery. As shown in Table 2, patients were divided into two groups for comparison of preoperative and postoperative data, with 47 in the TAP Group and 52 in the ntap Group. In the TAP group 22/47 (46.8%) underwent annuloplasty with the De Vega technique, 8) and 25/47 (53.2%) had placement of a rigid ring. The 52 patients in the ntap Group received mitral surgery alone. The severity of TR was compared echocardiographically before and after the surgery, and the change in severity of TR was examined. Pulmonary hypertension was defined as present when systolic pulmonary artery pressure (PAP) exceeded 40 mmhg as measured at cardiac catheterization prior to surgery. Follow-up by echocardiography was performed after 1, 3, and 6 months, and after that at least annually after hospital discharge. The follow-up period was defined as the time elapsed between surgery and the most recent echocardiographic examination. Data are expressed as mean ± standard deviation (SD), and independent continuous scale data were analyzed using the Mann-Whitney U test for nonparametric data. All of risk factors were analyzed using the chi-square test or Fisher s exact test. Cox regression analysis was used to evaluate univariate and multivariate predictors which could influence failure of improvement in TR. A p-value of less than 0.05 was considered significant. Results There were no operative deaths during mitral valve surgery, and all 99 patients are included in the analysis. As shown in Table 1 the subjects consisted of 38 males and 61 females, and their mean age was 65.4 ± Before the surgery 72 patients (72.7%) had atrial fibrillation (AF), 64 (64.6%) had heart failure with New York Ann Thorac Cardiovasc Surg Vol. 19, No. 6 (2013) 429

3 Ariyoshi T, et al. Table 2 Comparison of perioperative variables between TAP and ntap groups TAP (n = 47) ntap (n = 52) p value Age (years) 66.1 ± ± Gender Male Female Rheumatic etiology Atrial fibrillation <0.001 NYHA Class III Mitral stenosis Previous aortic or mitral surgery Left atrial dimension >60 mm LVEF <50% Systolic PAP >40 mmhg Preoperative TR grade < Postoperativve TR grade <0.001 Improved No change or worsening 3 17 Change of TR grade -2.1 ± ± 1.0 <0.001 NYHA: New York Heart Association; LVEF: left ventricular ejection fraction, PAP: pulmonary artery pressure; TR: tricuspid regurgitation Heart Association (NYHA) Class III, 18 (18.2%) had a previous history of aortic or mitral surgery, 34 (34.3%) had a left atrial dimension (LAD) greater than 60 mm, 11 (11.1%) had a left ventricular ejection fraction (LVEF) of less than 50%, and 47 (47.5%) had a systolic PAP of greater than 40 mm Hg. The mean follow-up period was 4.6 ± 2.7 years (range, 0.5 to 10.1 years). There were 6 late deaths during the follow-up period. The causes of death were as follows: cerebrovascular event in 2 patients, cancer in 1 patient, left ventricular failure 4.5 years postoperatively in 1 patient with grade 3 + TR, and unknown cause in 2 patients. No reoperation was performed in any patient throughout the follow-up period. Comparison between TAP and ntap Groups (Table 2) Preoperatively, significant differences were found between the two groups in frequency of rheumatic etiology, AF, MS, and previous aortic or mitral surgery, all of which were more common in the TAP group. As would be anticipated, the preoperative TR grade was significantly more advanced in the TAP group. Postoperatively the TAP Group was significantly different from the ntap group in the frequency of TR improvement and mean change of TR grade. In the TAP group (n = 47), TR improved in 44 patients (93.6%), but did not improve in the remaining 3 patients (6.4%), with worsening in 1 case and no change in the other 2. All 3 of these patients had undergone a De Vega operation for TAP, but all patients who had placement of a rigid ring showed improvement in TR. In the ntap group (n = 52) TR improved in 35 patients (67.3%), but did not improve in the remaining 17 patients (32.7%) during the follow-up period after surgery. Among the 17 patients who did not show improvement TR worsened to grade 3+ or higher in 6 patients (11.5%) and was grade 3+ in 4 patients and grade 4+ in 2 patients. Risk factor analysis for late TR in the ntap Group (Table 3) When characteristics of patients in the ntap group were compared for those who showed improvement of TR (Improved group) vs. those who failed to show improvement (No change or worsening group), univariate analysis identified rheumatic etiology, AF, MS and LAD >60 mm as risk factors for failure of postoperative improvement of TR. However the Cox regression analysis identified only AF as a risk factor. There were no significant differences between the two groups in age, gender, or proportion of patients having the following characteristics: heart failure of NYHA Class III, previous aortic or 430 Ann Thorac Cardiovasc Surg Vol. 19, No. 6 (2013)

4 Which Type of Secondary Tricuspid Regurgitation Accompanying Mitral Valve Disease Should Be Surgically Treated? Table 3 Variables influencing improvement of TR grade after mitral valve surgery in the ntap group Postoperative TR P-value Improved (n = 35) No change or worsening (n = 17) Univariate Multivariate Age (years) 62.7 ± ± Gender Male 18 5 Female Rheumatic etiology Atrial fibrillation < Mitral stenosis NYHA Class III Previous aortic or mitral surgery Left atrial dimension >60 mm LVEF <50% Systolic PAP >40 mmhg Preoperative TR grade TR: tricuspid regurgitation; NYHA: New York Heart Association; LVEF: left ventricular ejection fraction; PAP: pulmonary artery pressure mitral valve surgery, LVEF <50%, systolic PAP 40 mmhg, and preoperative TR grade. Patients with and without atrial fibrillation (AF) in the ntap Group (Table 4) Compared to patients without AF (n = 28), those with AF (n = 24) had a significantly higher frequency of a rheumatic etiology, larger LAD, and performance of mitral valve surgery, along with lesser improvement in postoperative TR. In patients without AF improvement of TR in the follow-up period was observed in 95.8% of patients, more than twice the figure of 42.9% observed in patients with AF. Discussion There is little consensus on the appropriateness of surgical treatment for secondary TR in patients with mitral valve disease. 3,9,10) The indications for surgical treatment of secondary TR with lesser grades in the range of 2+ is especially controversial. Accordingly, we carried out this study to consider the influence of surgical treatment of the mitral valve on secondary TR. We believe that it is important to determine the risk factors posed by residual TR in patients having mitral surgery without TAP, and to analyze which type of secondary TR should be treated surgically at the time of mitral surgery. For this purpose, subjects were limited to patients having secondary TR 2+ as a complication of mitral valve disease. To reduce the complexity of statistical analysis patients with congenital heart disease, DCM, ischemic heart disease, or infectious endocarditis before surgery were excluded from the study. In addition, patients who as a sequel to prior surgery developed a recurrence of MR, new-onset aortic valve disease, or coronary artery disease were excluded. The causes of secondary TR associated with mitral valve disease are complex and multifactorial. Although preoperative pulmonary hypertension is one of the important causes of secondary TR, it has been reported that it does not serve as a predictor of worsening of TR in the late phase after mitral valve surgery. 10) Pulmonary hypertension was also not identified as a predictor of worsening of TR in the late phase in our study in the ntap Group (Table 3). This may have resulted from the fact that PAP is generally anticipated to decrease after mitral valve surgery. 11) However, involvement of the right ventricle may also play a role. Reduction in right ventricular function may also aggravate TR by inducing tricuspid annular dilatation and right ventricular remodeling. 12,13) Through diminished pumping ability it may also reduce the severity of pulmonary hypertension in some cases, and contribute to the complex role played by preoperative pulmonary hypertension as a predictor of Ann Thorac Cardiovasc Surg Vol. 19, No. 6 (2013) 431

5 Ariyoshi T, et al. Table 4 Comparison between patients with and without atrial fibrillation in the ntap group Atrial fibrillation (n = 28) No Atrial fibrillation (n = 24) P-value Age 67.9 ± ± Female gender Rheumatic etiology NYHA Class III Left atrial dimension (mm) 58.0 ± ± 9.0 <0.001 >60 mm LVEF (%) 66.6 ± ± <50% Systolic PAP (mmhg) 40.5 ± ± >40 mmhg Mitral Surgery 0.01 valve repair replacement 17 6 Postoperative TR <0.001 Improved 12 (42.9%) 23 (95.8%) No change or worsening 16 (57.1%) 1 ( 4.2%) NYHA: New York Heart Association; LVEF: left ventricular ejection fraction; PAP: pulmonary artery pressure; TR: tricuspid regurgitation worsening of TR. In our series rheumatic etiology, AF, MS and LAD 60 mm were identified as risk factors for failure of improvement in the ntap group (Table 3). It has been reported that patients with a rheumatic etiology are likely to have abnormal morphology, including abnormal leaflet anatomy and annular degeneration and enlargement, which may contribute to TR occurring long after mitral surgery. 14) Tricuspid annular dilatation is also widely reported to be the most consistent and important predictor of TR. 5,15) Residual TR after mitral surgery may be caused mainly by annular dilatation, since correcting tricuspid dilatation with the TAP procedure resulted in a significantly better outcome (Table 2). In the current study underlying etiologies were restricted to rheumatic and non-rheumatic (degenerative) causes, since criteria were established to exclude from the study patients in several other categories. As shown in (Table 3), in the ntap Group TR improved in 35 of the 52 patients (67.3%) after mitral valve surgery, whereas there was no improvement in the other 17 patients (32.7%), and in fact 6 patients (11.5%) worsened. However, when the patients with a rheumatic etiology were excluded, only in 1 patient TR worsened during the follow-up period. These findings may provide some insight into which patients with TR should have a TAP procedure performed concurrently with mitral surgery. More recently, Yilmaz, et al. also reported on changes in severity of late TR in 699 patients who underwent mitral valve repair for severe MR, 16) and concluded that tricuspid valve surgery is rarely necessary for most patients since lesser degrees of TR in patients with degenerative mitral disease are unlikely to progress. Our results agree with this report in demonstrating the rare necessity of TAP for non-rheumatic (degenerative) patients. However multivariate analysis failed to identify rheumatic etiology as a significant risk factor for late TR, possibly due to the close relationship between rheumatic etiology and AF. In our study only AF was identified by multivariate analysis as a significant predictor of late phase worsening of TR in the ntap Group (Table 3). AF has previously been reported to predispose to worsening of TR after mitral valve surgery. 6,17 19) In fact, we observed improvement of TR in 95.8% of patients without AF, a value twofold greater than in patients with AF (Table 4). Occurrence of AF may result in elevation of left atrial pressure, and also induce enlargement of the right atrium and tricuspid annular dilatation, all potentially important factors in causing worsening of TR. Such a mechanism may in addition lead to significantly larger LAD in patients with AF than in those without AF, as observed in (Table 4). Dreyfus, et al. evaluated 311 patients undergoing mitral valve repair of whom 148 (47.6%) had tricuspid valve 432 Ann Thorac Cardiovasc Surg Vol. 19, No. 6 (2013)

6 Which Type of Secondary Tricuspid Regurgitation Accompanying Mitral Valve Disease Should Be Surgically Treated? repair because of a tricuspid annular diameter of 70 mm or greater, and concluded that tricuspid dilatation is the main and ongoing cause of late TR. 20) Our results are also congruent with this report, and are consistent with the view that a rheumatic etiology and AF induce tricuspid annular dilatation. The seeming discrepancies between the Dreyfus 20) and Yilmaz 16) reports about variations in the incidence of late TR are probably largely related to differences in case mix. It may be noted that the frequency of AF (29.3% vs. 17.5%) and rheumatic etiology (14.1% vs. 0%) were higher in the Dreyfus report. It remains unclear why patients with degenerative mitral disease have less severe late TR following mitral surgery. Alterations in tricuspid annular function and contractility could be at least in part responsible, but further research is needed to resolve this issue. When patients were divided into two groups according to the TAP procedure, there was a significantly higher frequency of AF and rheumatic etiology in the TAP Group than in the ntap Group (Table 2), possibly based in part upon the surgeon s clinical experience. Despite the presence of several risk factors for a poor outcome in the TAP Group, the postoperative TR grade and change of TR grade were significantly improved compared to the ntap group in the follow-up period. Although on multivariate analysis only AF was identified as a significant predictor of worsening TR in the late phase in the ntap Group, a rheumatic etiology is thought to be one of the important factors causing tricuspid annular dilatation and leading to residual TR. Because of the significant relationship between AF and rheumatic etiology in the ntap Group, the relative contributions of AF and rheumatic etiology to annular dilatation are somewhat uncertain. Although it remains unknown whether a rheumatic etiology is an independent risk factor for late TR after mitral valve surgery, the presence of preoperative AF is clearly important. Tricuspid annular dilatation induced by AF may be considered a progressive disease, and it is probably important to perform a TAP concurrently with mitral surgery to prevent late TR. In this retrospective study, the sample size was small and the follow-up period was not long enough to examine the effect of AF on residual TR. In addition, we were unable to measure accurately the tricuspid annular diameter. Preoperative assessment using echocardiography or cardiac magnetic resonance scans is problematic because these methods still depend upon preload and afterload conditions at the time of measurement. Intraoperative sizing also does not reflect conditions in situ in the beating heart. Further studies will be necessary on these points. Conclusion In conclusion, when TAP was not concurrently performed, TR did not improve after mitral valve surgery in one-third of patients with TR of grade 2+ at the time of mitral valve surgery. Furthermore, worsening of TR was observed in one-third of those patients who did not show improvement of TR. Since tricuspid valvuloplasty can be completed in a short period of time and the risk for adverse events is low, 21,22) our results suggest that concurrent tricuspid valvuloplasty should be performed at the time of mitral valve surgery in patients with TR of grade 2+ that accompanies mitral disease, especially in those having atrial fibrillation. Disclosure Statement We have no relevant financial interests in this manuscript. References 1) Bonow RO, Carabello BA, Chatterjee K, et al. ACC/ AHA 2006 guidelines for the management of patients with valvular heart disease. J Am Coll Cardiol 2006; 48:e ) Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007; 28: ) Braunwald NS, Ross J Jr, Morrow AG. Conservative management of tricuspid regurgitation in patients undergoing mitral valve replacement. Circulation 1967; 35: I ) Duran CM, Pomar JL, Colman T, et al. Is tricuspid valve repair necessary? J Thorac Cardiovasc Surg 1980; 80: ) Groves PH, Hall RJ. Late tricuspid regurgitation following mitral valve surgery. J Heart Valve Dis 1992; 1: ) Matsuyama K, Matsumoto M, Sugita T, et al. Predictors of residual tricuspid regurgitation after mitral valve surgery. Ann Thorac Surg 2003; 75: ) Yada I, Tani K, Shimono T, et al. Preoperative evaluation and surgical treatment for tricuspid regurgitation associated with acquired valvular heart disease. The Kay-Boyd method vs the Carpentier-Edwards ring method. J Cardiovasc Surg 1990; 31: Ann Thorac Cardiovasc Surg Vol. 19, No. 6 (2013) 433

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