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Impact of prosthesis–patient mismatch on tricuspid valve regurgitation and pulmonary hypertension following mitral valve replacement
International Journal of Cardiology 168 (2013) 4150–4154
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Impact of prosthesis–patient mismatch on tricuspid valve regurgitation and pulmonary hypertension following mitral valve replacement☆ Emiliano Angeloni a,⁎,1, Giovanni Melina a,1, Umberto Benedetto a,1, Antonino Roscitano a,1, Simone Refice a,1, Cesare Quarto b, Cosimo Comito a,1, Philippe Pibarot c, Riccardo Sinatra a,1 a b c
Sapienza, University of Rome, Department of Cardiac Surgery, Ospedale Sant'Andrea, Roma, Italy Department of Cardiothoracic Surgery, Harefield Hospital, London UK Québec Heart & Lung Institute, Québec, QC, Canada
a r t i c l e
i n f o
Article history: Received 2 July 2012 Received in revised form 2 July 2013 Accepted 13 July 2013 Available online 7 August 2013 Keywords: Mitral mismatch Tricuspid regurgitation Pulmonary hypertension Cardiovascular surgery
a b s t r a c t Background: Mitral PPM can be equated to residual mitral stenosis, which may halt the expected postoperative improvement of PH and concomitant functional tricuspid regurgitation (fTR). Aim of the present study is to evaluate the impact of mitral prosthesis–patient mismatch (PPM) on late tricuspid valve regurgitation and pulmonary hypertension (PH). Methods: A total of 210 patients undergoing isolated mitral valve replacement (MVR) were investigated. Mitral valve effective orifice area was determined by the continuity equation and indexed for body surface area (EOAi) and PPM was defined as EOAi ≤ 1.2 cm2/m2. Pulmonary hypertension (PH) was defined as systolic pulmonary artery pressure (sPAP) N 40 mmHg. Clinical and echocardiographic follow-up (median 27 months) was 100% completed. A total of 88/210 (42%) patients developed mitral PPM. Results: There were no significative differences in baseline and operative characteristics between patients with and without PPM. At follow-up, the prevalence of fTR ≥ 2+ (57%vs.22%; p = 0.0001), and PH (62%vs.24%; p b 0.0001) were significantly higher in patients with PPM. On multivariable regression analysis, EOAi (p b 0.0001) and preoperative left ventricular (LV) end-diastolic diameter (p b 0.0001) were found to be independently associated with fTR decrease after MVR. In addition, EOAi (p b 0.0001) and LV ejection fraction (p b 0.0001) were independently associated with PH decrease after MVR. No significant differences in mortality rates were found between patients having or not PPM. Conclusions: This study shows that mitral PPM is associated with the persistence of fTR and PH following MVR. These findings support the realization of tricuspid valve annuloplasty when PPM is anticipated at the time of operation. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Previous studies reported that prosthesis–patient mismatch (PPM) is associated with worse hemodynamics, less regression of left ventricular hypertrophy, more cardiac events, and higher mortality rates after aortic valve replacement [1–4]. However, PPM following mitral valve replacement (MVR) has been less investigated. Previous studies reported that mitral PPM is not uncommon, ranging between 30 and 85% when in vivo evaluation of effective orifice area (EOA) is performed [5–7]. Two studies reported that mitral PPM is independently associated ☆ Dr. Pibarot received research grants from Edwards Lifesciences LLC (Irvine, CA) and Medtronic Inc. (Minneapolis, MN). Other authors have nothing to disclose. ⁎ Corresponding author at: University of Rome “La Sapienza”, Policlinico Sant'Andrea, Department of Cardiac Surgery, Via di Grottarossa 1035, 00189 Rome, Italy. Tel.: + 39 0633775593; fax: + 39 0633775483. E-mail address: [email protected] (E. Angeloni). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.07.116
with increased mortality [5,6], whereas another one found no significant impact on survival [7]. Mitral PPM can be equated to residual mitral stenosis resulting in increased trans-mitral gradients, increased left atrial pressure, and pulmonary hypertension (PH). These factors may lead to right ventricular dilatation/dysfunction and to atrial fibrillation, which may, in turn, lead to tricuspid annulus dilatation and functional tricuspid regurgitation (fTR). Indeed, tricuspid regurgitation is not uncommon in the settings of mitral valve disease. At least moderate fTR is present in more than one-third of patients presenting with mitral stenosis and in 15% of patients with mitral regurgitation [8]. Such patients are more likely to have NYHA functional class III or IV [9], and the persistence of fTR after MVR predicts poor outcome [10]. After earlier reports supporting conservative treatment of fTR [11], it was subsequently demonstrated that fTR might not resolve after isolated MVR [12,13]. Several factors (age, pulmonary hypertension, atrial fibrillation, and tricuspid annular diameter) may hinder the postoperative improvement of fTR [14,15]. Hence, current guidelines [16,17]
E. Angeloni et al. / International Journal of Cardiology 168 (2013) 4150–4154
recommend tricuspid valve repair in patients undergoing mitral valve surgery in the presence of severe tricuspid regurgitation (class I), and in the presence of moderate TR or of dilated tricuspid annulus (class IIa/b). The objective of this study was to investigate the impact of mitral PPM on fTR and pulmonary arterial hypertension following MVR.
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with the use of the continuous variable, i.e. EOAi rather than with the use of the dichotomous variable (PPM vs. no PPM).
3. Results 3.1. Perioperative analysis
2. Methods This study was reviewed and approved by the Institutional Review Board of the University of Rome, and a waiver of consent was granted. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. 2.1. Patients and variables We retrospectively reviewed a consecutive series of 446 patients who underwent elective isolated MVR for mitral valve disease at Sant'Andrea Hospital (“Sapienza”, University of Rome) from May 2004 to May 2011. Patients with previous cardiac surgery, and concomitant CABG or other valvular procedures were excluded; yielding to a final sample size of 210 patients. Data were prospectively collected and recorded in an electronic database, and clinical follow-up was completed with routine outpatient clinics. Patients who did not present at the visit were contacted by telephone, and all symptoms, mortality, and any complications that occurred during follow-up were recorded. All patients underwent a full median sternotomy and operation performed on cardio-pulmonary bypass. Cardiac arrest was obtained by means of antegrade cold blood cardioplegia, repeated every 15 minutes. The prostheses used in this series were Perimount Magna (Edwards Lifesciences LLC, Irvine, CA), CarboMedics Mechanical (Sorin-CarboMedics Inc, Austin, TX), and St. Jude Medical Standard Mechanical (St. Jude Medical Inc, St. Paul, MN). At least posterior chordal preservation was attempted in every patient. 2.2. Doppler-echocardiographic assessment Clinical and echocardiographic assessment were performed prior to MVR and at 12months after operation, and once a year afterwards. At each visit, all patients underwent a complete M-mode, bi-dimensional and Doppler trans-thoracic echocardiographic assessment with the use of a Sonos 7500 systems (Phillips Medical Ultrasound). All echocardiographic studies were reviewed in a core laboratory and independently reviewed by two echocardiographists. Left ventricular ejection fraction (LVEF) was calculated by using the Simpson's biplane method. Tricuspid regurgitation was diagnosed with color Doppler measurement of regurgitant jet flow area [18]. Non univocal findings at color Doppler measurement of tricuspid regurgitant jet flow area were assessed by means of vena contracta width and PISA radius, and TR degree was adjudicated consequently: TR N 2+ if vena contracta width N 6 mm, and PISA radius N 5 mm [18]. The intra- and inter-observer variability for the measurement of fTR in the echo corelab were 11 ± 6% and 10 ± 9%, respectively. The in-vivo prosthetic valve effective orifice area (EOA) was calculated with the use of the continuity equation, using the stroke volume measured in the LV outflow tract divided by the integral of the mitral valve transprosthetic velocity-time integral during diastole. Calculated values of EOA were then compared to the normal reference values of EOA provided for each type and size of prosthetic valve in the guidelines of the American Society of Echocardiography [19]. Prosthetic valve dysfunction was considered to be present when the measured EOA was b the normal reference EOA – 1SD. The indexed EOA (EOAi) was calculated by dividing the measured EOA by the patient's body surface area at the time of follow-up. Mitral PPM was defined [20] as an EOAi b 1.2 cm2/m2. The systolic pulmonary artery pressure was calculated by adding the systolic right ventricular pressure derived from the tricuspid regurgitation to the estimated right atrial pressure. Right atrial pressure was estimated from the diameter and the degree of collapse of the inferior vena cava during inspiration [5]. Pulmonary arterial hypertension was defined as a systolic pulmonary artery pressure (sPAP) N 40 mm Hg [5,7]. 2.3. Statistical analysis Data were prospectively collected and recorded in an electronic database; statistical analysis was performed using the Statistical Package for the Social Sciences, version 11.0 (SPSS, Chicago, IL). Variables were checked for normality by means of the Kolmogorov–Smirnov test for normal distribution and normality was accepted when p ≤ 0.05. Continuous data are expressed as the mean and standard deviation; categorical data are expressed as the percentage, comparisons were made using the 2-sample t and the χ2 or the Fischer exact tests, respectively. Univariate correlation to identify factors associated with fTR decrease following MVR was tested by means of one-way-analysis of variance (ANOVA). Age, gender, follow-up time and clinically relevant variables with a p value b0.2 on univariable analysis were incorporated into the multivariable stepwise model. As dealing with longitudinal data, mixed-effect regression models were adopted. In the univariable and multivariable regression analyses, data were expressed as regression coefficient (β) and p-value, statistical significance was defined as a p value ≤ 0.05. For these analyses, PPM was expressed
A total of 210 patients undergoing isolated MVR were investigated and 101/210 (48%) of those had fTR = 2+ not addressed at surgery. Overall, 88/210 (42%) patients developed mitral PPM but none had prosthetic valve dysfunction. As expected, prosthesis–patient mismatch resulted in significant differences in both mean EOAi (0.93 ± 0.08 vs. 1.28 ± 0.07 cm2/m2 for patients with or without PPM, respectively; p b 0.0001), and mean mitral trans-prosthetic gradients (4.7 ± 1.1 vs. 3.2 ± 2.5 mmHg for patients with or without PPM, respectively; p b 0.0001). At baseline, there was no significant difference between PPM and no-PPM groups (Table 1). Nearly 51% of patients (107/210) underwent surgery because of mitral stenosis, 29/210 (14%) patients had instead mixed mitral disease, and 74/210 (35%) patients had mitral regurgitation. These patients having mitral regurgitation did not receive mitral valve repair because of severe Barlow degeneration, presence of calcification, and presence of shortened chordate and/or papillary muscles; depending on primary surgeon decision at the time of surgery. No difference between PPM groups was found with regards to the mitral pathology and etiology: degenerative 74% vs. 73% (p = 0.99), rheumatic in 12% vs. 8% (p = 0.46), and endocarditis in 14% vs. 19% (p = 0.44); for patient with and without PPM, respectively. Atrial fibrillation was present in 79/210 (38%) patients and, depending on the history of the disease and the left atrial diameter (b50 mm), 18/79 (23%) of those (total of 18/210 or 8.5%) received a Maze procedure associated to MVR (no difference between patients having or not PPM, Table 1). Table 1 Perioperative data according to the presence of prosthesis–patient mismatch. Perioperative Variables
PPM (n = 88)
No-PPM (n = 122)
p value
Baseline characteristics Age, years Male gender, n (%) Body surface area, m2 Hypertension, n (%) Diabetes mellitus, n (%) Chronic renal disease, n (%) Chronic pulmonary disease, n (%) Cerebrovascular disease, n (%) History of Atrial fibrillation, n (%) LVEF, % LVEDD, mm RV long axis, mm LA diameter, mm Tricuspid annulus diameter, mm Prevalence of fTR = 2+, n (%) Systolic PA Pressure, mmHg Prevalence of PH, n (%) NYHA functional class, mean
67.4 ± 11.2 61 (69) 1.84 ± 0.29 52 (59) 13 (15) 3 (3.4) 8 (9) 4 (4.5) 33 (38) 63.5 ± 12.2 50.2 ± 7.6 73 ± 9 51 ± 12 42 ± 8 42 (48) 48 ± 15 63 (72) 3.7 ± 1.4
67.3 ± 12.5 85 (70) 1.93 ± 0.41 73 (60) 20 (16) 5 (4.1) 12 (10) 6 (5) 46 (38) 64.1 ± 14.6 49.8 ± 7.1 72 ± 11 51 ± 13 43 ± 7 58 (48) 47 ± 12 86 (70) 3.6 ± 1.7
0.86 0.74 0.08 0.92 0.66 0.72 0.82 0.86 0.79 0.47 0.38 0.42 0.87 0.34 0.84 0.49 0.47 0.82
Operative characteristics Mean prosthetic valve size, mm Mechanical prosthesis, n (%) Posterior chordal preservation, n (%) Associated Maze procedure, n (%) Operative mortality, n (%)
27.8 ± 2.6 59 (67) 36 (41) 8 (9) 4 (4.5)
29.6 ± 2.4 76 (62) 51 (42) 10 (9) 5 (4)
b0.0001 0.54 0.77 0.84 0.81
Continuous variables are expressed as the mean ± standard deviation, categorical variables as percentages. PPM: Prosthesis–patient mismatch; LVEF: Left ventricular ejection fraction; LVEDD: Left ventricular end-diastolic volume; RV: Right ventricular; LA: Left atrial; fTR: Functional tricuspid regurgitation; PA:Pulmonary artery; PH: Pulmonary hypertension; EOAi: Effective orifice area index; NYHA New York Heart Association.
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Leaflet apparatus preservation was attempted in every case, but at least posterior chordal preservation was actual only in 87/210 (41%) patients, due to the degree of calcification; there was no difference in leaflet preservation rate between PPM groups. At baseline there was no difference in the grade of fTR present in those patients with and without PPM (Fig. 1), in particular fTR = 2 + was present in 42/88 (48%) patients from the PPM group and 58/122 (48%) patients from the no-PPM group (p = 0.84). No difference was found neither in the prevalence of PH: 72% or 63/ 88 vs. 70% or 86/122 at baseline (p = 0.47), and 68% or 60/88 vs. 66% or 81/122 early after surgery (p = 0.46) for patients with and without PPM, respectively (Fig. 2). Overall operative mortality was 4.3% (9/210), and no statistically significant difference was found between patients showing or not PPM (4/88 or 4.5% vs. 5/122 or 4.1% respectively; p = 0.81) 3.2. Follow-up evaluation All patients had complete clinical and echocardiographic follow-up (median 27 months; range 12–48 months); data are presented in Table 2. At follow-up, the prevalence of fTR ≥ 2+ was significantly higher in patients with PPM (57%) compared to those without PPM (22%; p = 0.0001; Fig. 1). Furthermore, the prevalence of PH was also higher in patients with PPM (61% vs. 24%; p b 0.0001; Fig. 2); incidence of AF, instead, was similar: 30/88 (34%) among PPM patients, and 39/ 122 (32%) among patients without PPM (p = 0.87). A trend towards lesser right ventricular remodeling was found among patients with PPM, but it did not reach statistical significance. Tricuspid annular dilatation was similar at baseline (42 ± 8 mm vs. 43 ± 7 mm; p = 0.34) but there was a trend towards larger annulus dimension at follow-up (41 ± 9 mm vs. 39 ± 7 mm for PPM and no PPM group, respectively; p = 0.07). Univariate analysis of variance was performed to identify the predictors of postoperative fTR decrease (preoperative fTR–fTR at last followup). On univariable analysis, factors significantly associated with reduced fTR decrease were: larger preoperative left atrial diameter (p = 0.001), larger LV end-diastolic diameter (p = 0.001), lesser degree of mitral regurgitation (p = 0.001), lower LV ejection fraction (p = 0.01), and smaller prosthetic valve EOAi (i.e. higher degree of PPM; p = 0.0001). On multivariable regression analysis (Table 3), only smaller EOAi (p b 0.0001) and larger LV end-diastolic diameter (p b 0.0001) were found to be independently associated with smaller decrease in fTR after MVR. The model was well calibrated and showed satisfactory goodness-of-fit (model χ2 = 61, p b 0.0001; R2 adjusted = 0.76). A second linear regression analysis (Table 4) was performed to identify the factors associated with postoperative regression in PH (preoperative sPAP – sPAP at last follow-up) as dependent variable. On multivariable regression, only EOAi (p b 0.0001) and preoperative LV
Fig. 2. Prevalence of pulmonary hypertension (PH) stratified for the occurrence of prosthesis–patient mismatch (PPM) at baseline, early postoperatively and late after mitral valve replacement. PH: Pulmonary hypertension; PPM: Prosthesis–patient mismatch.
ejection fraction (p b 0.0001) were found to be independently associated with the postoperative regression of PH. The model was well calibrated and showed satisfactory goodness-of-fit (model χ2 = 66, p b 0.0001; R2 adjusted = 0.69). 3.3. Clinical impact Before surgery mean NYHA class was 3.7 ± 1.4 vs. 3.6 ± 1.7 for PPM and no-PPM group, respectively (p = 0.82). At follow-up, both mean NYHA class (2.6 ± 1.8 vs. 1.4 ± 0.8; p b 0.0001), and mean NYHA class decrease (−1.2 ± 2.3 vs. −2.2 ± 1.6; p = 0.0003) were significantly different in patients with PPM. Overall, 2/210 (0.9%) patients underwent re-operation because of massive tricuspid regurgitation and at rest dyspnoea; both patients were in the mitral PPM group. No statistically significant difference was found in mortality rates between groups (11/88 or 12.5% vs. 15/122 or 12.3% for patients with or without PPM, respectively; p = 0.83). 4. Discussion 4.1. Main findings The main finding of this study was that mitral PPM is associated with lesser regression of both fTR and PH following isolated MVR. These associations were independent of other preoperative and operative variables. In addition, patients with PPM also exhibited less improvement in NYHA functional class, thus further emphasising the clinical relevance of these results. There were no significant differences with regards to mortality between PPM and no-PPM groups, but it has to be pointed out that the
Fig. 1. Degrees of functional tricuspid regurgitation (fTR) stratified for the occurrence of prosthesis–patient mismatch (PPM) at baseline, and late after mitral valve replacement. fTR: Functional tricuspid regurgitation; PPM: Prosthesis–patient mismatch.
E. Angeloni et al. / International Journal of Cardiology 168 (2013) 4150–4154 Table 2 Follow-up data according to the presence of prosthesis–patient mismatch. Variables at Follow-up
PPM (n = 88)
NO PPM (n = 122)
p value
EOAi, cm2/m2 Mean mitral trans-prosthetic gradient, mmHg fTR ≥ 2+ prevalence, n (%) fTR decrease, median (95%CI) PH prevalence, n (%) Mean sPAP, mmHg sPAP decrease, mean NYHA functional class, mean NYHA class decrease, mean LVEDD, mm RV long axis, mm Tricuspid annulus diameter, mm Mean LVEF, % Mortality, n (%)
0.93 ± 0.08 4.7 ± 1.1
1.28 ± 0.07 3.2 ± 2.5
b0.0001 b0.0001
50 (57) −1.1 (−1.9 to 0.5) 54 (61) 41 ± 9 −2 ± 8 2.6 ± 1.8 −1.2 ± 2.3 49.6 ± 9.5 70 ± 12 41 ± 9
27 (22) −2.2 (−2.7 to −1.5) 29 (24) 31 ± 6 −10 ± 5 1.4 ± 0.8 −2.2 ± 1.6 48.1 ± 8.4 67 ± 14 39 ± 7
0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 0.0003 0.2 0.28 0.07
66.3 ± 14.2 11 (12.5)
67.1 ± 12.6 15 (12)
0.55 0.83
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Table 3 Multivariable regression analysisa of variables associated with tricuspid regurgitation decrease after mitral valve replacement. Variables
β coefficient
95% CI
p value
Age Male gender Preoperative LVEDD Preoperative LVEF Preoperative LA diameter Preoperative MR degree Prosthetic valve EOAi
−0.12 −0.04 −0.41 0.17 −0.22 0.10 0.32
−0.24 to 0.10 −0.18 to 0.22 −0.57 to −0.24 −0.01 to 0.25 −0.31 to 0.16 −0.02 to 0.15 0.19 to 0.52
0.09 0.32 b0.0001 0.08 0.08 0.11 b0.0001
CI: Confidence interval; LVEDD: Left ventricular end-diastolic diameter; LVEF: Left ventricular ejection fraction; LA: Left atrial; MR, Mitral regurgitation; EOAi: Indexed effective orifice area. a Model χ2 = 61, p b 0.0001; R2 adjusted = 0.76.
4.4. Strategies to avoid mitral PPM
Continuous variables are expressed as the mean ± standard deviation or median and its 95% confidence interval, categorical variables as percentages. PPM: Prosthesis–patient mismatch; EOAi: Effective orifice area index; fTR: Functional tricuspid regurgitation; CI: Confidence interval; PH: Pulmonary hypertension; sPAP: Systolic pulmonary artery pressure; NYHA New York Heart Association; LVEDD: Left ventricular end-diastolic volume; RV: Right ventricular; LVEF: Left ventricular ejection fraction.
median follow-up period was of 2 years, which is may be too short to investigate differences in mortality rates [7].
4.2. Expected benefits of MVR The surgical management of patients undergoing mitral valve surgery with concomitant fTR remains controversial. Mitral valve replacement itself should ideally improve pulmonary hypertension and tricuspid regurgitation without increasing operative times and risk. Conflicting results were reported with respect to concomitant tricuspid surgery [21,22]. It is well established that postoperative persistence and/or worsening of fTR is associated with worse outcomes [17,23]. This is mainly due to the fact that fTR is a consequence of adverse right ventricular remodelling, caused by chronic pressure overload, which finally results in dilatation of the tricuspid annulus [24,25]. The isolated treatment of the mitral valve only decreases afterload, but it does not correct tricuspid dilatation nor does it directly affect preload or right ventricular function [22]. Consequently, complete reversal of right ventricular remodelling may not occur, and tricuspid regurgitation may not decrease in many patients [23].
4.3. Mechanisms for the occurrence of late TR In a recent study from our Institution [15], we found that tricuspid annular dilatation is a key factor in the decision of combining or not tricuspid annuloplasty with mitral surgery. In the present study, conducted in a much larger cohort of patients with some degree of tricuspid regurgitation but not undergoing surgical correction, we found that, with similar baseline tricuspid annulus diameter, those patients with mitral PPM had lesser improvement of fTR and PH after MVR. Beside these findings, patients with PPM also showed a trend towards lesser right ventricular reverse remodelling, which likely results from the higher sPAP and more important fTR found in those patients. These factors may contribute to the persistence of tricuspid annular dilatation, which may further entertain the fTR. The results of this study underline the importance of avoiding PPM in patients undergoing isolated MVR, especially when fTR, tricuspid annular dilatation, severe PH or right ventricular dilatation are present.
In mitral valve surgery, the best option to avoid PPM is the performance of mitral valve repair, which is not always applicable. Indeed, some patients require MVR and, such is the case, in light of the results of this study, the realization of concomitant tricuspid valve annuloplasty should be performed in patients with preexisting fTR in whom PPM is anticipated at the time of operation. The similar mortality rates (early and at follow-up) of patients with and without PPM, suggest that mitral prosthesis–patient mismatch does not affect survival, as previously reported from other authors [7]. In the latter, we have to underline that the median follow-up time of our study was of only 27 months, whilst relevant tricuspid regurgitation can appear as late as 10 to 20 years after mitral valve replacement [8], and its clinical relevance can take even more time to result in heart failure and eventually death. 4.5. Limitations This is not a randomized study and, despite the use of a priori definitions of end points and covariates, selection bias or unidentified confounders may have influenced the results. As our findings are based upon an observational cohort, they may not necessarily be generalizable to all patients. Follow-up period was not long enough to assess differences in mortality, but this was not the primary outcome of the study. Further studies are needed to confirm and extend these findings. 5. Conclusion The results of the present study suggest that mitral PPM may hinder the regression of both fTR and PH in patients undergoing isolated MVR. This negative effect was also associated with worse functional capacity. These findings provide a strong impetus for the application of preventive strategies at the time of operation to avoid PPM or reduce it severity and for the realization of tricuspid valve annuloplasty when PPM is anticipated at the time of operation. Table 4 Multivariable regression analysisa of variables associated with systolic pulmonary artery pressure decrease after mitral valve replacement. Variables
β coefficient
95% CI
p value
Age Male gender Preoperative LVEDD Preoperative LVEF Preoperative LA diameter Preoperative MR degree Prosthetic valve EOAi
−0.10 −0.07 −0.28 0.37 −0.16 0.18 0.30
−0.21 to 0.15 −0.16 to 0.24 −0.36 to 0.14 0.25 to 0.51 −0.24 to 0.18 −0.26 to 0.17 0.17 to 0.48
0.12 0.46 0.07 b0.0001 0.10 0.09 b0.0001
CI: Confidence interval; LVEDD: Left ventricular end-diastolic diameter; LVEF: Left ventricular ejection fraction; LA: Left atrial; MR, Mitral regurgitation; EOAi: Indexed effective orifice area. a Model χ2 = 66, p b 0.0001; R2 adjusted = 0.69.
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Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 2006;48: e1-148. Vahanian A, Baumgartner H, Bax J, et al. Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology; ESC Committee for Practice Guidelines. 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;28:230–68. Lancellotti P, Moura L, Pierard LA, et al. European Association of Echocardiography. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). Eur J Echocardiogr 2010;11:307–32. Zoghbi WA, Chambers JB, Dumesnil JG, et al. American Society of Echocardiography's Guidelines and Standards Committee; Task Force on Prosthetic Valves; American College of Cardiology Cardiovascular Imaging Committee; Cardiac Imaging Committee of the American Heart Association; European Association of Echocardiography; European Society of Cardiology; Japanese Society of Echocardiography; Canadian Society of Echocardiography; American College of Cardiology Foundation; American Heart Association; European Association of Echocardiography; European Society of Cardiology; Japanese Society of Echocardiography; Canadian Society of Echocardiography.Recommendations for evaluation of prosthetic valves with echocardiography and doppler ultrasound: a report From the American Society of Echocardiography's Guidelines and Standards Committee and the Task Force on Prosthetic Valves. J Am Soc Echocardiogr 2009;22:975–1014. Pibarot P, Dumesnil JG. Prosthesis–patient mismatch: definition, clinical impact and prevention. Heart 2006;92:1022–9. Chan V, Burwash IG, Lam BK, et al. Clinical and echocardiographic impact of functional tricuspid regurgitation repair at the time of mitral valve replacement. Ann Thorac Surg 2009;88:1209–15. Dreyfus GD, Corbi PJ, Chan KM, Bahrami T. Secondary tricuspid regurgitation or dilatation: which should be the criteria for surgical repair? Ann Thorac Surg 2005;79:127–32. Song H, Kang DH, Kim JH, et al. Percutaneous mitral valvuloplasty versus surgical treatment in mitral stenosis with severe tricuspid regurgitation. Circulation 2007;116:I246–50. Fukuda S, Gillinov AM, Song JM, et al. Echocardiographic insights into atrial and ventricular mechanisms of functional tricuspid regurgitation. Am Heart J 2006;152: 1208–14. Ton-Nu TT, Levine RA, Handschumacher MD, et al. Geometric determinants of functional tricuspid regurgitation: insights from 3-dimensional echocardiography. Circulation 2006;114:143–9.
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Impact of prosthesis–patient mismatch on tricuspid valve regurgitation and pulmonary hypertension following mitral valve replacement☆ Emiliano Angeloni a,⁎,1, Giovanni Melina a,1, Umberto Benedetto a,1, Antonino Roscitano a,1, Simone Refice a,1, Cesare Quarto b, Cosimo Comito a,1, Philippe Pibarot c, Riccardo Sinatra a,1 a b c
Sapienza, University of Rome, Department of Cardiac Surgery, Ospedale Sant'Andrea, Roma, Italy Department of Cardiothoracic Surgery, Harefield Hospital, London UK Québec Heart & Lung Institute, Québec, QC, Canada
a r t i c l e
i n f o
Article history: Received 2 July 2012 Received in revised form 2 July 2013 Accepted 13 July 2013 Available online 7 August 2013 Keywords: Mitral mismatch Tricuspid regurgitation Pulmonary hypertension Cardiovascular surgery
a b s t r a c t Background: Mitral PPM can be equated to residual mitral stenosis, which may halt the expected postoperative improvement of PH and concomitant functional tricuspid regurgitation (fTR). Aim of the present study is to evaluate the impact of mitral prosthesis–patient mismatch (PPM) on late tricuspid valve regurgitation and pulmonary hypertension (PH). Methods: A total of 210 patients undergoing isolated mitral valve replacement (MVR) were investigated. Mitral valve effective orifice area was determined by the continuity equation and indexed for body surface area (EOAi) and PPM was defined as EOAi ≤ 1.2 cm2/m2. Pulmonary hypertension (PH) was defined as systolic pulmonary artery pressure (sPAP) N 40 mmHg. Clinical and echocardiographic follow-up (median 27 months) was 100% completed. A total of 88/210 (42%) patients developed mitral PPM. Results: There were no significative differences in baseline and operative characteristics between patients with and without PPM. At follow-up, the prevalence of fTR ≥ 2+ (57%vs.22%; p = 0.0001), and PH (62%vs.24%; p b 0.0001) were significantly higher in patients with PPM. On multivariable regression analysis, EOAi (p b 0.0001) and preoperative left ventricular (LV) end-diastolic diameter (p b 0.0001) were found to be independently associated with fTR decrease after MVR. In addition, EOAi (p b 0.0001) and LV ejection fraction (p b 0.0001) were independently associated with PH decrease after MVR. No significant differences in mortality rates were found between patients having or not PPM. Conclusions: This study shows that mitral PPM is associated with the persistence of fTR and PH following MVR. These findings support the realization of tricuspid valve annuloplasty when PPM is anticipated at the time of operation. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Previous studies reported that prosthesis–patient mismatch (PPM) is associated with worse hemodynamics, less regression of left ventricular hypertrophy, more cardiac events, and higher mortality rates after aortic valve replacement [1–4]. However, PPM following mitral valve replacement (MVR) has been less investigated. Previous studies reported that mitral PPM is not uncommon, ranging between 30 and 85% when in vivo evaluation of effective orifice area (EOA) is performed [5–7]. Two studies reported that mitral PPM is independently associated ☆ Dr. Pibarot received research grants from Edwards Lifesciences LLC (Irvine, CA) and Medtronic Inc. (Minneapolis, MN). Other authors have nothing to disclose. ⁎ Corresponding author at: University of Rome “La Sapienza”, Policlinico Sant'Andrea, Department of Cardiac Surgery, Via di Grottarossa 1035, 00189 Rome, Italy. Tel.: + 39 0633775593; fax: + 39 0633775483. E-mail address: [email protected] (E. Angeloni). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.07.116
with increased mortality [5,6], whereas another one found no significant impact on survival [7]. Mitral PPM can be equated to residual mitral stenosis resulting in increased trans-mitral gradients, increased left atrial pressure, and pulmonary hypertension (PH). These factors may lead to right ventricular dilatation/dysfunction and to atrial fibrillation, which may, in turn, lead to tricuspid annulus dilatation and functional tricuspid regurgitation (fTR). Indeed, tricuspid regurgitation is not uncommon in the settings of mitral valve disease. At least moderate fTR is present in more than one-third of patients presenting with mitral stenosis and in 15% of patients with mitral regurgitation [8]. Such patients are more likely to have NYHA functional class III or IV [9], and the persistence of fTR after MVR predicts poor outcome [10]. After earlier reports supporting conservative treatment of fTR [11], it was subsequently demonstrated that fTR might not resolve after isolated MVR [12,13]. Several factors (age, pulmonary hypertension, atrial fibrillation, and tricuspid annular diameter) may hinder the postoperative improvement of fTR [14,15]. Hence, current guidelines [16,17]
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recommend tricuspid valve repair in patients undergoing mitral valve surgery in the presence of severe tricuspid regurgitation (class I), and in the presence of moderate TR or of dilated tricuspid annulus (class IIa/b). The objective of this study was to investigate the impact of mitral PPM on fTR and pulmonary arterial hypertension following MVR.
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with the use of the continuous variable, i.e. EOAi rather than with the use of the dichotomous variable (PPM vs. no PPM).
3. Results 3.1. Perioperative analysis
2. Methods This study was reviewed and approved by the Institutional Review Board of the University of Rome, and a waiver of consent was granted. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. 2.1. Patients and variables We retrospectively reviewed a consecutive series of 446 patients who underwent elective isolated MVR for mitral valve disease at Sant'Andrea Hospital (“Sapienza”, University of Rome) from May 2004 to May 2011. Patients with previous cardiac surgery, and concomitant CABG or other valvular procedures were excluded; yielding to a final sample size of 210 patients. Data were prospectively collected and recorded in an electronic database, and clinical follow-up was completed with routine outpatient clinics. Patients who did not present at the visit were contacted by telephone, and all symptoms, mortality, and any complications that occurred during follow-up were recorded. All patients underwent a full median sternotomy and operation performed on cardio-pulmonary bypass. Cardiac arrest was obtained by means of antegrade cold blood cardioplegia, repeated every 15 minutes. The prostheses used in this series were Perimount Magna (Edwards Lifesciences LLC, Irvine, CA), CarboMedics Mechanical (Sorin-CarboMedics Inc, Austin, TX), and St. Jude Medical Standard Mechanical (St. Jude Medical Inc, St. Paul, MN). At least posterior chordal preservation was attempted in every patient. 2.2. Doppler-echocardiographic assessment Clinical and echocardiographic assessment were performed prior to MVR and at 12months after operation, and once a year afterwards. At each visit, all patients underwent a complete M-mode, bi-dimensional and Doppler trans-thoracic echocardiographic assessment with the use of a Sonos 7500 systems (Phillips Medical Ultrasound). All echocardiographic studies were reviewed in a core laboratory and independently reviewed by two echocardiographists. Left ventricular ejection fraction (LVEF) was calculated by using the Simpson's biplane method. Tricuspid regurgitation was diagnosed with color Doppler measurement of regurgitant jet flow area [18]. Non univocal findings at color Doppler measurement of tricuspid regurgitant jet flow area were assessed by means of vena contracta width and PISA radius, and TR degree was adjudicated consequently: TR N 2+ if vena contracta width N 6 mm, and PISA radius N 5 mm [18]. The intra- and inter-observer variability for the measurement of fTR in the echo corelab were 11 ± 6% and 10 ± 9%, respectively. The in-vivo prosthetic valve effective orifice area (EOA) was calculated with the use of the continuity equation, using the stroke volume measured in the LV outflow tract divided by the integral of the mitral valve transprosthetic velocity-time integral during diastole. Calculated values of EOA were then compared to the normal reference values of EOA provided for each type and size of prosthetic valve in the guidelines of the American Society of Echocardiography [19]. Prosthetic valve dysfunction was considered to be present when the measured EOA was b the normal reference EOA – 1SD. The indexed EOA (EOAi) was calculated by dividing the measured EOA by the patient's body surface area at the time of follow-up. Mitral PPM was defined [20] as an EOAi b 1.2 cm2/m2. The systolic pulmonary artery pressure was calculated by adding the systolic right ventricular pressure derived from the tricuspid regurgitation to the estimated right atrial pressure. Right atrial pressure was estimated from the diameter and the degree of collapse of the inferior vena cava during inspiration [5]. Pulmonary arterial hypertension was defined as a systolic pulmonary artery pressure (sPAP) N 40 mm Hg [5,7]. 2.3. Statistical analysis Data were prospectively collected and recorded in an electronic database; statistical analysis was performed using the Statistical Package for the Social Sciences, version 11.0 (SPSS, Chicago, IL). Variables were checked for normality by means of the Kolmogorov–Smirnov test for normal distribution and normality was accepted when p ≤ 0.05. Continuous data are expressed as the mean and standard deviation; categorical data are expressed as the percentage, comparisons were made using the 2-sample t and the χ2 or the Fischer exact tests, respectively. Univariate correlation to identify factors associated with fTR decrease following MVR was tested by means of one-way-analysis of variance (ANOVA). Age, gender, follow-up time and clinically relevant variables with a p value b0.2 on univariable analysis were incorporated into the multivariable stepwise model. As dealing with longitudinal data, mixed-effect regression models were adopted. In the univariable and multivariable regression analyses, data were expressed as regression coefficient (β) and p-value, statistical significance was defined as a p value ≤ 0.05. For these analyses, PPM was expressed
A total of 210 patients undergoing isolated MVR were investigated and 101/210 (48%) of those had fTR = 2+ not addressed at surgery. Overall, 88/210 (42%) patients developed mitral PPM but none had prosthetic valve dysfunction. As expected, prosthesis–patient mismatch resulted in significant differences in both mean EOAi (0.93 ± 0.08 vs. 1.28 ± 0.07 cm2/m2 for patients with or without PPM, respectively; p b 0.0001), and mean mitral trans-prosthetic gradients (4.7 ± 1.1 vs. 3.2 ± 2.5 mmHg for patients with or without PPM, respectively; p b 0.0001). At baseline, there was no significant difference between PPM and no-PPM groups (Table 1). Nearly 51% of patients (107/210) underwent surgery because of mitral stenosis, 29/210 (14%) patients had instead mixed mitral disease, and 74/210 (35%) patients had mitral regurgitation. These patients having mitral regurgitation did not receive mitral valve repair because of severe Barlow degeneration, presence of calcification, and presence of shortened chordate and/or papillary muscles; depending on primary surgeon decision at the time of surgery. No difference between PPM groups was found with regards to the mitral pathology and etiology: degenerative 74% vs. 73% (p = 0.99), rheumatic in 12% vs. 8% (p = 0.46), and endocarditis in 14% vs. 19% (p = 0.44); for patient with and without PPM, respectively. Atrial fibrillation was present in 79/210 (38%) patients and, depending on the history of the disease and the left atrial diameter (b50 mm), 18/79 (23%) of those (total of 18/210 or 8.5%) received a Maze procedure associated to MVR (no difference between patients having or not PPM, Table 1). Table 1 Perioperative data according to the presence of prosthesis–patient mismatch. Perioperative Variables
PPM (n = 88)
No-PPM (n = 122)
p value
Baseline characteristics Age, years Male gender, n (%) Body surface area, m2 Hypertension, n (%) Diabetes mellitus, n (%) Chronic renal disease, n (%) Chronic pulmonary disease, n (%) Cerebrovascular disease, n (%) History of Atrial fibrillation, n (%) LVEF, % LVEDD, mm RV long axis, mm LA diameter, mm Tricuspid annulus diameter, mm Prevalence of fTR = 2+, n (%) Systolic PA Pressure, mmHg Prevalence of PH, n (%) NYHA functional class, mean
67.4 ± 11.2 61 (69) 1.84 ± 0.29 52 (59) 13 (15) 3 (3.4) 8 (9) 4 (4.5) 33 (38) 63.5 ± 12.2 50.2 ± 7.6 73 ± 9 51 ± 12 42 ± 8 42 (48) 48 ± 15 63 (72) 3.7 ± 1.4
67.3 ± 12.5 85 (70) 1.93 ± 0.41 73 (60) 20 (16) 5 (4.1) 12 (10) 6 (5) 46 (38) 64.1 ± 14.6 49.8 ± 7.1 72 ± 11 51 ± 13 43 ± 7 58 (48) 47 ± 12 86 (70) 3.6 ± 1.7
0.86 0.74 0.08 0.92 0.66 0.72 0.82 0.86 0.79 0.47 0.38 0.42 0.87 0.34 0.84 0.49 0.47 0.82
Operative characteristics Mean prosthetic valve size, mm Mechanical prosthesis, n (%) Posterior chordal preservation, n (%) Associated Maze procedure, n (%) Operative mortality, n (%)
27.8 ± 2.6 59 (67) 36 (41) 8 (9) 4 (4.5)
29.6 ± 2.4 76 (62) 51 (42) 10 (9) 5 (4)
b0.0001 0.54 0.77 0.84 0.81
Continuous variables are expressed as the mean ± standard deviation, categorical variables as percentages. PPM: Prosthesis–patient mismatch; LVEF: Left ventricular ejection fraction; LVEDD: Left ventricular end-diastolic volume; RV: Right ventricular; LA: Left atrial; fTR: Functional tricuspid regurgitation; PA:Pulmonary artery; PH: Pulmonary hypertension; EOAi: Effective orifice area index; NYHA New York Heart Association.
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Leaflet apparatus preservation was attempted in every case, but at least posterior chordal preservation was actual only in 87/210 (41%) patients, due to the degree of calcification; there was no difference in leaflet preservation rate between PPM groups. At baseline there was no difference in the grade of fTR present in those patients with and without PPM (Fig. 1), in particular fTR = 2 + was present in 42/88 (48%) patients from the PPM group and 58/122 (48%) patients from the no-PPM group (p = 0.84). No difference was found neither in the prevalence of PH: 72% or 63/ 88 vs. 70% or 86/122 at baseline (p = 0.47), and 68% or 60/88 vs. 66% or 81/122 early after surgery (p = 0.46) for patients with and without PPM, respectively (Fig. 2). Overall operative mortality was 4.3% (9/210), and no statistically significant difference was found between patients showing or not PPM (4/88 or 4.5% vs. 5/122 or 4.1% respectively; p = 0.81) 3.2. Follow-up evaluation All patients had complete clinical and echocardiographic follow-up (median 27 months; range 12–48 months); data are presented in Table 2. At follow-up, the prevalence of fTR ≥ 2+ was significantly higher in patients with PPM (57%) compared to those without PPM (22%; p = 0.0001; Fig. 1). Furthermore, the prevalence of PH was also higher in patients with PPM (61% vs. 24%; p b 0.0001; Fig. 2); incidence of AF, instead, was similar: 30/88 (34%) among PPM patients, and 39/ 122 (32%) among patients without PPM (p = 0.87). A trend towards lesser right ventricular remodeling was found among patients with PPM, but it did not reach statistical significance. Tricuspid annular dilatation was similar at baseline (42 ± 8 mm vs. 43 ± 7 mm; p = 0.34) but there was a trend towards larger annulus dimension at follow-up (41 ± 9 mm vs. 39 ± 7 mm for PPM and no PPM group, respectively; p = 0.07). Univariate analysis of variance was performed to identify the predictors of postoperative fTR decrease (preoperative fTR–fTR at last followup). On univariable analysis, factors significantly associated with reduced fTR decrease were: larger preoperative left atrial diameter (p = 0.001), larger LV end-diastolic diameter (p = 0.001), lesser degree of mitral regurgitation (p = 0.001), lower LV ejection fraction (p = 0.01), and smaller prosthetic valve EOAi (i.e. higher degree of PPM; p = 0.0001). On multivariable regression analysis (Table 3), only smaller EOAi (p b 0.0001) and larger LV end-diastolic diameter (p b 0.0001) were found to be independently associated with smaller decrease in fTR after MVR. The model was well calibrated and showed satisfactory goodness-of-fit (model χ2 = 61, p b 0.0001; R2 adjusted = 0.76). A second linear regression analysis (Table 4) was performed to identify the factors associated with postoperative regression in PH (preoperative sPAP – sPAP at last follow-up) as dependent variable. On multivariable regression, only EOAi (p b 0.0001) and preoperative LV
Fig. 2. Prevalence of pulmonary hypertension (PH) stratified for the occurrence of prosthesis–patient mismatch (PPM) at baseline, early postoperatively and late after mitral valve replacement. PH: Pulmonary hypertension; PPM: Prosthesis–patient mismatch.
ejection fraction (p b 0.0001) were found to be independently associated with the postoperative regression of PH. The model was well calibrated and showed satisfactory goodness-of-fit (model χ2 = 66, p b 0.0001; R2 adjusted = 0.69). 3.3. Clinical impact Before surgery mean NYHA class was 3.7 ± 1.4 vs. 3.6 ± 1.7 for PPM and no-PPM group, respectively (p = 0.82). At follow-up, both mean NYHA class (2.6 ± 1.8 vs. 1.4 ± 0.8; p b 0.0001), and mean NYHA class decrease (−1.2 ± 2.3 vs. −2.2 ± 1.6; p = 0.0003) were significantly different in patients with PPM. Overall, 2/210 (0.9%) patients underwent re-operation because of massive tricuspid regurgitation and at rest dyspnoea; both patients were in the mitral PPM group. No statistically significant difference was found in mortality rates between groups (11/88 or 12.5% vs. 15/122 or 12.3% for patients with or without PPM, respectively; p = 0.83). 4. Discussion 4.1. Main findings The main finding of this study was that mitral PPM is associated with lesser regression of both fTR and PH following isolated MVR. These associations were independent of other preoperative and operative variables. In addition, patients with PPM also exhibited less improvement in NYHA functional class, thus further emphasising the clinical relevance of these results. There were no significant differences with regards to mortality between PPM and no-PPM groups, but it has to be pointed out that the
Fig. 1. Degrees of functional tricuspid regurgitation (fTR) stratified for the occurrence of prosthesis–patient mismatch (PPM) at baseline, and late after mitral valve replacement. fTR: Functional tricuspid regurgitation; PPM: Prosthesis–patient mismatch.
E. Angeloni et al. / International Journal of Cardiology 168 (2013) 4150–4154 Table 2 Follow-up data according to the presence of prosthesis–patient mismatch. Variables at Follow-up
PPM (n = 88)
NO PPM (n = 122)
p value
EOAi, cm2/m2 Mean mitral trans-prosthetic gradient, mmHg fTR ≥ 2+ prevalence, n (%) fTR decrease, median (95%CI) PH prevalence, n (%) Mean sPAP, mmHg sPAP decrease, mean NYHA functional class, mean NYHA class decrease, mean LVEDD, mm RV long axis, mm Tricuspid annulus diameter, mm Mean LVEF, % Mortality, n (%)
0.93 ± 0.08 4.7 ± 1.1
1.28 ± 0.07 3.2 ± 2.5
b0.0001 b0.0001
50 (57) −1.1 (−1.9 to 0.5) 54 (61) 41 ± 9 −2 ± 8 2.6 ± 1.8 −1.2 ± 2.3 49.6 ± 9.5 70 ± 12 41 ± 9
27 (22) −2.2 (−2.7 to −1.5) 29 (24) 31 ± 6 −10 ± 5 1.4 ± 0.8 −2.2 ± 1.6 48.1 ± 8.4 67 ± 14 39 ± 7
0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 0.0003 0.2 0.28 0.07
66.3 ± 14.2 11 (12.5)
67.1 ± 12.6 15 (12)
0.55 0.83
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Table 3 Multivariable regression analysisa of variables associated with tricuspid regurgitation decrease after mitral valve replacement. Variables
β coefficient
95% CI
p value
Age Male gender Preoperative LVEDD Preoperative LVEF Preoperative LA diameter Preoperative MR degree Prosthetic valve EOAi
−0.12 −0.04 −0.41 0.17 −0.22 0.10 0.32
−0.24 to 0.10 −0.18 to 0.22 −0.57 to −0.24 −0.01 to 0.25 −0.31 to 0.16 −0.02 to 0.15 0.19 to 0.52
0.09 0.32 b0.0001 0.08 0.08 0.11 b0.0001
CI: Confidence interval; LVEDD: Left ventricular end-diastolic diameter; LVEF: Left ventricular ejection fraction; LA: Left atrial; MR, Mitral regurgitation; EOAi: Indexed effective orifice area. a Model χ2 = 61, p b 0.0001; R2 adjusted = 0.76.
4.4. Strategies to avoid mitral PPM
Continuous variables are expressed as the mean ± standard deviation or median and its 95% confidence interval, categorical variables as percentages. PPM: Prosthesis–patient mismatch; EOAi: Effective orifice area index; fTR: Functional tricuspid regurgitation; CI: Confidence interval; PH: Pulmonary hypertension; sPAP: Systolic pulmonary artery pressure; NYHA New York Heart Association; LVEDD: Left ventricular end-diastolic volume; RV: Right ventricular; LVEF: Left ventricular ejection fraction.
median follow-up period was of 2 years, which is may be too short to investigate differences in mortality rates [7].
4.2. Expected benefits of MVR The surgical management of patients undergoing mitral valve surgery with concomitant fTR remains controversial. Mitral valve replacement itself should ideally improve pulmonary hypertension and tricuspid regurgitation without increasing operative times and risk. Conflicting results were reported with respect to concomitant tricuspid surgery [21,22]. It is well established that postoperative persistence and/or worsening of fTR is associated with worse outcomes [17,23]. This is mainly due to the fact that fTR is a consequence of adverse right ventricular remodelling, caused by chronic pressure overload, which finally results in dilatation of the tricuspid annulus [24,25]. The isolated treatment of the mitral valve only decreases afterload, but it does not correct tricuspid dilatation nor does it directly affect preload or right ventricular function [22]. Consequently, complete reversal of right ventricular remodelling may not occur, and tricuspid regurgitation may not decrease in many patients [23].
4.3. Mechanisms for the occurrence of late TR In a recent study from our Institution [15], we found that tricuspid annular dilatation is a key factor in the decision of combining or not tricuspid annuloplasty with mitral surgery. In the present study, conducted in a much larger cohort of patients with some degree of tricuspid regurgitation but not undergoing surgical correction, we found that, with similar baseline tricuspid annulus diameter, those patients with mitral PPM had lesser improvement of fTR and PH after MVR. Beside these findings, patients with PPM also showed a trend towards lesser right ventricular reverse remodelling, which likely results from the higher sPAP and more important fTR found in those patients. These factors may contribute to the persistence of tricuspid annular dilatation, which may further entertain the fTR. The results of this study underline the importance of avoiding PPM in patients undergoing isolated MVR, especially when fTR, tricuspid annular dilatation, severe PH or right ventricular dilatation are present.
In mitral valve surgery, the best option to avoid PPM is the performance of mitral valve repair, which is not always applicable. Indeed, some patients require MVR and, such is the case, in light of the results of this study, the realization of concomitant tricuspid valve annuloplasty should be performed in patients with preexisting fTR in whom PPM is anticipated at the time of operation. The similar mortality rates (early and at follow-up) of patients with and without PPM, suggest that mitral prosthesis–patient mismatch does not affect survival, as previously reported from other authors [7]. In the latter, we have to underline that the median follow-up time of our study was of only 27 months, whilst relevant tricuspid regurgitation can appear as late as 10 to 20 years after mitral valve replacement [8], and its clinical relevance can take even more time to result in heart failure and eventually death. 4.5. Limitations This is not a randomized study and, despite the use of a priori definitions of end points and covariates, selection bias or unidentified confounders may have influenced the results. As our findings are based upon an observational cohort, they may not necessarily be generalizable to all patients. Follow-up period was not long enough to assess differences in mortality, but this was not the primary outcome of the study. Further studies are needed to confirm and extend these findings. 5. Conclusion The results of the present study suggest that mitral PPM may hinder the regression of both fTR and PH in patients undergoing isolated MVR. This negative effect was also associated with worse functional capacity. These findings provide a strong impetus for the application of preventive strategies at the time of operation to avoid PPM or reduce it severity and for the realization of tricuspid valve annuloplasty when PPM is anticipated at the time of operation. Table 4 Multivariable regression analysisa of variables associated with systolic pulmonary artery pressure decrease after mitral valve replacement. Variables
β coefficient
95% CI
p value
Age Male gender Preoperative LVEDD Preoperative LVEF Preoperative LA diameter Preoperative MR degree Prosthetic valve EOAi
−0.10 −0.07 −0.28 0.37 −0.16 0.18 0.30
−0.21 to 0.15 −0.16 to 0.24 −0.36 to 0.14 0.25 to 0.51 −0.24 to 0.18 −0.26 to 0.17 0.17 to 0.48
0.12 0.46 0.07 b0.0001 0.10 0.09 b0.0001
CI: Confidence interval; LVEDD: Left ventricular end-diastolic diameter; LVEF: Left ventricular ejection fraction; LA: Left atrial; MR, Mitral regurgitation; EOAi: Indexed effective orifice area. a Model χ2 = 66, p b 0.0001; R2 adjusted = 0.69.
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