Effect of Aortic Valve Replacement for Aortic Stenosis on Severity of Mitral Regurgitation

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1 ORIGINAL ARTICLES: ADULT CARDIAC SURGERY: The Annals of Thoracic Surgery CME Program is located online at To take the CME activity related to this article, you must have either an STS member or an individual nonmember subscription to the journal. Effect of Aortic Valve Replacement for Aortic Stenosis on Severity of Mitral Regurgitation Frédéric Vanden Eynden, MD, Denis Bouchard, MD, Ismaïl El-Hamamsy, MD, Ady Butnaru, MD, Philippe Demers, MD, Michel Carrier, MD, Louis P. Perrault, MD, Jean-Claude Tardif, MD, and Michel Pellerin, MD Department of Cardiac Surgery, Free University of Brussels, Brussels, Belgium; and Departments of Cardiovascular Surgery and Medicine, Montreal Heart Institute, Montreal, Quebec, Canada Background. Surgically addressing moderate mitral regurgitation (MR) at the time of aortic valve replacement (AVR) for aortic stenosis remains uncertain. The purpose of this study was to examine the change in moderate (2 ) or moderate-severe (3 ) MR after isolated AVR for aortic stenosis to determine preoperative factors predictive of improvement in MR. Methods. Using an institutional databank of prospectively collected data, all patients undergoing isolated AVR for aortic stenosis with moderate (2 ) to moderatesevere (3 ) MR between 1994 and 1996 at the Montreal Heart Institute were evaluated. Results. Eighty patients with preoperative and postoperative transthoracic echocardiographic follow-up were identified. Preoperative MR was moderate (2 ) in 78 patients (97.5%) and moderate-severe (3 ) in 2 patients (2.5%). Mitral regurgitation was classified as rheumatic (32%), ischemic (32%), functional (21%), and myxomatous (15%). At 1-year follow-up transthoracic echocardiography, MR improved by 1 or 2 grades in 29 patients (35%), was unchanged in 44 (55%), and worsened in 7 (10%). On multivariate analysis, isolated ischemic and functional MR were the only preoperative factors predictive of MR improvement after AVR (p 0.01): 54% of ischemic and 44% of functional MR patients showed improvement in MR after AVR compared with 23% of rheumatic and 17% of myxomatous MR patients. Conclusions. Etiology of MR was a significant prognostic factor for improvement in MR grade. Since there was little improvement in the rheumatoid and myxomatous group, replacement or repair should strongly be considered. For functional and ischemic mitral regurgitation, a surgical correction should be performed on an individual basis. (Ann Thorac Surg 2007;83: ) 2007 by The Society of Thoracic Surgeons Aortic valve replacement (AVR) for aortic stenosis is the most frequently performed surgery for valvular heart disease. Mitral regurgitation (MR) is a common finding in patients with aortic valve stenosis, with an incidence as high as 67% reported in the literature [1]. Whether a concomitant mitral procedure should be performed is usually not an issue when MR is mild; most surgeons will not expose the patient to excessive morbidity for grade 1 MR nor let a patient with grade 4 MR leave the operating room untreated. But when MR is moderate, the question is whether a second valve should be replaced or repaired at the same time. In the literature, functional mitral regurgitation appears to have a better prognosis than structural regurgitation after AVR. Because the concurrent replacement of both valves is associated with higher postoperative mortality (5% to 12.5%) Accepted for publication Dec 27, Address correspondence to Dr Bouchard, Department of Surgery, Montreal Heart Institute, 5000 Bélanger Est, Montreal, Quebec, Canada H1T1C8; denis.bouchard@icm-mhi.org. and morbidity rates [2, 3], mitral valve surgery could be avoided if it were possible to reliably predict that MR would improve after AVR. In contrast, combined valve surgery would be warranted for patients with significant or progressive MR after isolated AVR. The purpose of our study was to evaluate in a cohort of patients (1) the changes in MR severity that occur after isolated aortic valve replacement for aortic stenosis for moderate (2 ) and moderate-to-severe (3 ) mitral regurgitation; (2) the clinical and echocardiographic findings that may be preoperative predictors of MR improvement after aortic valve surgery, focusing on the cause of mitral regurgitation; and (3) the long-term survival benefit of improvement in MR after isolated AVR. Patients and Methods Patient Population and Data Collection A retrospective review of prospectively collected data from 80 consecutive patients who underwent isolated AVR from January 1994 to December 1996 was conducted 2007 by The Society of Thoracic Surgeons /07/$32.00 Published by Elsevier Inc doi: /j.athoracsur

2 1280 VANDEN EYNDEN ET AL Ann Thorac Surg AORTIC VALVE REPLACEMENT EFFECT ON MR SEVERITY 2007;83: Table 1. Preoperative Patient Characteristics MR Classification n 80 n 26 n 12 n 26 n 16 Sex male (%) 42 (52) 13 (50) 6 (50) 19 (73) 5 (31) Age Body surface area Smoking (%) 17 (21) 10 (38) 2 (20) 3 (11) 2 (12) Hypertension (%) 50 (62) 15 (57) 7 (58) 16 (61) 12 (75) Diabetes mellitus (%) 10 (13) 0 2 (20) 6 (23) 2 (12) Aortic bicuspidy (%) 9 (11) 4 (15) 2 (20) 1 (3) 2 (12) AVA Septum LVED diameter Left atrium diameter LVEF NYHA (%) 1 1 (1) (4) (30) 8 (31) 1 (8) 7 (27) 8 (50) 3 49 (62) 17 (65) 8 (67) 17 (65) 7 (43) 4 6 (7) 1 (4) 3 (25) 1 (4) 1 (7) MGAV AVA aortic valve area; LVED left ventricular end-diastolic; LVEF left ventricular ejection fraction; MGAV mean gradient across the aortic valve; MR mitral regurgitation; NYHA New York Heart Association. at the Montreal Heart Institute. To be included, patients had to have moderate or moderate-to-severe MR on preoperative echocardiography and complete echographic follow-up at 1 year. Exclusion criteria were severe aortic regurgitation, moderate or severe mitral stenosis, prior mitral valve surgery, and associated surgery (other than coronary artery bypass graft surgery) at the time of AVR. Charts were reviewed for preoperative characteristics and operative characteristics; the indexed effective orifice area (EOAi) was calculated according to the literature [4]. Echocardiographic tapes (when available) or detailed reports were reviewed by a single echocardiographist. All patients had an echographic study before surgery and 1 year after AVR. Survival analysis was performed based on follow-up conducted at the valve clinic; last follow-up visit and deceased date were considered for analysis. This study was approved by the Montreal Heart Institute Ethics Committee. Consent was waived by the Committee. Echocardiographic Analysis The peak and mean gradients across the aortic valve were calculated using the Bernoulli equation, and the aortic valve area was assessed using the continuity equation. The severity of MR was assessed using several color-flow and spectral Doppler criteria, including MR area, MR/left atrium (LA) area ratio (the area of the regurgitant jet relative to the LA size), antegrade mitral flow velocity, and pulmonary venous flow, together with other two-dimensional criteria of MR severity (left ventricle dimensions and function, LA dimensions, and mitral valve morphology). Attenuation of the systolic component of the pulmonary veins (PV) flow generally resulted in grading the MR as moderate, whereas systolic wave inversion resulted in considering the MR as severe. Two-dimensional and M-mode echocardiography were used to detect the underlying cause of MR. Thickening and calcification of the leaflet tissue and subvalvular Table 2. Operative Characteristics MR Classification n 80 n 26 n 12 n 26 n 16 Biological valves 51 (63%) 16 (61%) 7 (58%) 16 (61%) 12 (75%) Mechanical valves 29 (27%) 10 (39%) 5 (42%) 10 (39%) 4 (25%) EOAi Lowest EOAi CABG associated 25 (31%) 1 (4%) 1 (8%) 22 (84%) 1 (7%) Aortoplasty 5 (6%) 3 (12%) 1 (8%) 1 (4%) 0 CABG coronary artery bypass graft surgery; EOAi indexed effective orifice area.

3 Ann Thorac Surg VANDEN EYNDEN ET AL 2007;83: AORTIC VALVE REPLACEMENT EFFECT ON MR SEVERITY 1281 Table 3. Echographic Characteristics at One Year n 80 n 26 n 12 n 26 n 16 Septum LVED diameter Left atrium diameter LVEF MGAV LVED left ventricular end-diastolic diameter; LVEF left ventricular ejection fraction; MGAV mean gradient across the aortic valve. apparatus with restricted leaflet motion and commissural fusion combined with mild mitral stenosis and a history of rheumatic fever were criteria retained for rheumatic origin. Myxomatous origin was recognized when the mitral valve met the criteria for classic or nonclassic mitral leaflet prolapse (Carpentier type II): a maximum superior displacement of one or both mitral leaflets of more than 2 mm relative to the line connecting the annular hinge points during systole, whether the leaflet was superior or inferior to 5 mm. When valvular anatomy was normal and MR was caused by failure in coaptation of mitral leaflets because of their restricted motion (Carpentier type IIIb) and there was a history of myocardial infarction, the MR was attributed to an ischemic origin. When none of these criteria was met, the MR was targeted as functional (Carpentier type I). Mitral regurgitation severity was scored as follows: absent or trace 0, mild 1, moderate 2, moderate to severe 3, and severe 4 [5, 6]. A change in MR was considered significant when there was at least a 1 score difference between preoperative and postoperative studies. When no morphologic abnormality was found, the MR was classified as functional. The presence or absence of mitral annulus calcification was determined with twodimensional parasternal and apical views. The left ventricular end-diastolic diameter and the thickness of the interventricular septum and posterior wall were measured by two-dimensionally guided M-mode echocardiography using standard American Society of Echocardiography criteria. Left atrial diameter was measured using M-mode in the parasternal view. Left ventricular ejection fraction was determined with the apical views and the modified Simpson formula. Because changes in MR severity in the immediate and short-term postoperative period may not reflect those in a more stable setting, we elected to focus on the postoperative echocardiogram performed 1 year after isolated AVR. Statistical Methods Univariate analysis of preoperative patient history and physical characteristics and echocardiographic findings was performed for the overall group. Student s t test was used to compare continuous variables and Fisher s exact test, to compare categorical variables. Univariate analysis was used to determine possible predictors of MR evolution, using a p value of less than 0.05 as a cutoff for significance. Significant factors were then analyzed in a multivariate logistic regression analysis to determine predictors of regurgitation improvement. Survival analysis was done using the Kaplan-Meier method, and statistical significance was obtained using the Breslow test. A p value of less than 0.05 was considered significant. The data were analyzed using the statistical package program SPSS 13 (SPSS, Chicago, Illinois). Results Patient Characteristics The study group consisted of 80 patients (38 women, 42 men, aged years) who underwent AVR for aortic Table 4. Mitral Regurgitation Before and After Aortic Valve Replacement n 80 n 26 n 12 n 26 n 16 Mitral regurgitation preoperatively Moderate Moderate to severe Mitral regurgitation postoperatively Trace Mild Moderate Moderate to severe Severe

4 1282 VANDEN EYNDEN ET AL Ann Thorac Surg AORTIC VALVE REPLACEMENT EFFECT ON MR SEVERITY 2007;83: stenosis and had moderate or moderate-to-severe mitral regurgitation on preoperative echocardiography. Table 1 lists the preoperative clinical and echocardiographic characteristics. Preoperatively, the majority of patients were in New York Heart Association (NYHA) class II or III (73 patients, 91.2%). Left ventricular ejection fraction was 50% 13%. Gross pathology examination revealed 9 bicuspid aortic valves (11.2%). Morphologic intrinsic changes of the mitral apparatus (either myxomatous or rheumatic) were found in 38 patients (47%), 26 (33%) having ischemic MR and 14 (20%) having functional MR. Operative Characteristics Table 2 lists the operative characteristics. The majority of the prosthetic valves were biological (51 patients, 63%). A coronary artery bypass graft procedure was associated in 25 of 80 patients (31%), and 22 of these 25 (88%) were in the ischemic MR group. Five patients had an aortoplasty that consisted of a pericardial patch enlargement of the aorta. The mean EOAi was 0.86 cm 2 /m 2, and there were no annular enlargement. Echocardiographic Changes After AVR Postoperative echocardiographic findings at 1 year are listed in Table 3. As expected, there was a significant change (p ) in mean aortic gradient from mm Hg before AVR to mm Hg after AVR. The interventricular septum end-diastolic thickness did not significantly regress. The left ventricular enddiastolic diameter and the atrial diameter did not change appreciably after operation. For the whole group, the left ventricular ejection fraction was preserved. Severity of Mitral Regurgitation Before and After AVR The preoperative and postoperative degrees of MR for all patients are listed in Table 4. The degree of MR decreased in 29 of 80 patients (36%), remained unchanged in 44 of 80 patients (55%), and worsened in 7 of 80 patients (9%) 1 year after AVR. Improvement was more frequent in the ischemic MR group, 14 of 26 (54%), and in the functional MR group, 7 of 16 (43%), than in the rheumatoid group, 6 of 26 (23%), or the myxomatous group, 2 of 12 (17%). The change in the distribution of MR severity before and after AVR was significant (p ). The distribution of postoperative MR according to preoperative MR is shown in Figure 1. Predictors of Improvement in MR After AVR Preoperative risk factors such as age (p 0.40), the presence of hypertension (p 0.28), sex (p 0.47), and NYHA status (p 0.5) did not correlate with postoperative change in MR. Preoperative echographic studies showed no correlation of MR evolution with septum thickness (p 0.3), left ventricular end-diastolic diameter (p 0.5), or left auricular diameter (p 0.8). Preoperative left ventricular ejection fraction was suspected as a prognostic factor but did not reach statistical significance on multivariate analysis (p 0.19). Postoperative EOAi (p 0.68) and concomitant CABG surgery (p 0.71) had no effect on MR regression after Fig 1. Changes in mitral regurgitation (MR) after aortic valve replacement are shown. Improvement in postoperative MR was found at 1 year. (Open bars improved; solid bars same or worse.) AVR. The etiology of mitral regurgitation before AVR, namely, ischemic, functional, rheumatic, or myxomatous, was independently correlated with MR improvement (p 0.013). Survival Analysis Survival of patients according to etiology of MR (Fig 2) rheumatic plus myxomatous and ischemic plus functional was similar at 10 years after isolated AVR (p 0.867). Patients who showed MR improvement after isolated AVR had a better 10-year survival than did patients who had no changes or had deteriorating MR (p 0.072; Fig 3). Comment The present study suggests that, overall, a third of patients showed a significant improvement of the degree of MR 1 year after isolated AVR. Patients with MR improvement were more likely to have ischemic or functional MR at the time of AVR and these patients had better 10-year survival rates compared with patients with stable or worse MR. In patients with severe aortic stenosis, concomitant MR either may be caused by morphologic changes of the mitral valve or may be secondary to aortic stenosis and increased afterload and left ventricular dysfunction or a combination of both. The degree of MR depends on the regurgitant orifice and the systolic pressure gradient between the left ventricle and left atrium. The former may be affected by ventricular remodeling after AVR; the latter may be affected by replacing a stenotic aortic valve, thereby lowering the left ventricular systolic pressure [7]. Given the morphologic and physiologic modification after AVR, the degree of MR might improve. Whether the mitral valve should be repaired or replaced during the same operation in patients with severe aortic stenosis undergoing AVR is controversial when considering patients with moderate (2 ) or moderate-tosevere (3 ) MR. Because the concurrent replacement of

5 Ann Thorac Surg VANDEN EYNDEN ET AL 2007;83: AORTIC VALVE REPLACEMENT EFFECT ON MR SEVERITY 1283 Fig 2. Survival according to mitral regurgitation etiology. Vertical hatch marks represent censored patients. (AVR aortic valve replacement; isch/funct ischemic/functional; rheum/funct rheumatic/functional.) both valves is associated with higher postoperative mortality (5% to 12.5%) and morbidity [2, 3], mitral valve surgery could be avoided if it were possible to reliably predict in which circumstances MR would improve after AVR. In contrast, combined valve surgery would be warranted for patients with unchanged but significant or progressive MR after isolated AVR. Thus, it is crucial to predict which are the preoperative clinical and echocardiographic factors influencing the improvement or deterioration of MR in patients undergoing AVR. In our study, we had a significant change in the distribution of MR severity before and after AVR toward improvement: 36% of patients improved by 1 or 2 on the scale of MR at 1 year. This finding is consistent with other reports in the literature including all types of MR. Tunick and associates [8] studied MR evolution at a mean of 58 days after AVR. Half of the patients had structural valve lesions, and of the 44 patients studied, 11 had moderate MR. In those 11 patients, 10 showed an improvement of MR after AVR [8]. In contrast, Adams and associates [9] had only 4 patients improving in the sample of 16 patients with moderate MR at a mean of 176 days after surgery. Given the sample size, they could not identify prognostic factors. More recently, Brasch and associates [10] studied 27 patients, 16 of them having grade 2 or 3 MR, and 9 (44%) of those experienced an improvement of MR. Larger left ventricular mass was the only significant prognostic of MR improvement when considering the whole group at mean follow-up of 2.2 months [10]. Etiology of MR was not reported, but 96% had mitral calcifications and 33% had thickening of the leaflets. Bareirro and coworkers [11] reported 80% improvement Fig 3. Survival according to postoperative mitral regurgitation (MR) improvement. Vertical hatch marks represent censored patients. (AVR aortic valve replacement.)

6 1284 VANDEN EYNDEN ET AL Ann Thorac Surg AORTIC VALVE REPLACEMENT EFFECT ON MR SEVERITY 2007;83: in the functional group and 50% improvement in the myxomatous group, but of the 70 patients studied, only 37 had a postoperative echography. We showed that the most significant prognostic factor was the etiology of MR: ischemic and functional MR improved at echocardiographic analysis 1 year after isolated AVR whereas rheumatic and myxomatous disease remained stable or deteriorated. Although etiology was a strong prognostic factor, we had also 5 of 26 patients (23%) improved in the rheumatoid group and 2 of 12 (17%) in the myxomatous group. The MR amendment has been more extensively studied in the literature in the functional group [12 14]. Seven patients (7 of 16, 43%) in our study with functional MR improved, as shown by Moazami and associates [15] after a mean 818 days of follow-up. This figure was confirmed by Absil and colleagues [16] (40 patients of a cohort of 58 patients with grade 2 or 3 improved) and by Ruel and associates [17]. Ruel showed that functional MR improved in 68.4% of patients with moderate MR and no additional identified risk factors (left atrial diameter 5 cm, atrial fibrillation, mean aortic gradient 40 mm Hg), in 63.5% if one risk factor was present, and in 44.4% if two risk factors were present. In our study, the most important improvement was seen in the ischemic group, occurring in 14 patients (14 of 26, 54%). Christenson and associates [18] specifically assessed this issue, showing improved MR in 19 of 21 patients (90%) with AVR and CABG-associated procedure and improved MR in 12 of 19 patients (63%) in the AVR only group [18]. Patients with MR improvement after isolated AVR seemed to have a better 10-year survival compared with patients with stable or deteriorating MR. This observation did not reach statistical significance (p 0.072), and other confounding variables such as left ventricular ejection fraction were not assessed; however, it is consistent with other reports in the literature in which the burden of MR, even mild, is an independent prognostic factor for worse long-term survival as seen in the setting of ventricular dysfunction [19] or ischemic mitral regurgitation [20]. In conclusion, our patients undergoing isolated AVR for aortic stenosis with significant MR before surgery showed that MR improved in ischemic and functional MR whereas MR deteriorated in rheumatic and myxomatous etiology at 1-year echographic follow-up. The decision to repair or replace the mitral valve at the time of AVR remains difficult, but preoperative echocardiographic analysis of the mitral valve morphology gives the surgeon the most important prognostic factor for the change in MR severity: the etiology of MR. 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