Background: Structural changes to the mitral annulus occur following aortic valve replacement (AVR) for severe aortic stenosis which may influence functional mitral regurgitation (MR). Methods: A retrospective review of 44 patients who underwent open AVR for aortic stenosis at a single center from 2010-2013 was performed. Patients undergoing concomitant aortic root surgery or with severe MR were excluded. MR was evaluated with preoperative and postoperative transthoracic echocardiograms. Univariate and multivariable analyses were performed to assess for factors associated with postoperative MR improvement and worsening. Results: Prior to AVR, none had severe MR, 5% (2 patients) had moderate, 9% (4 patients) mild-to-moderate, 46% (20 patients) mild, and 23% (9 patients) trace MR. Of patients with pre-operative MR, 44% (16 patients) experienced improvement of MR. Six patients had worsening of MR and the remaining 22 patients had no change. Cases of more severe MR were more likely to improve compared with mild or trace MR (P = 0.04). MR worsening was significantly more likely in patients with bicuspid aortic valves (83% vs. 24%; P = 0.004), and with larger aortic annulus diameters (P = 0.03). MR worsening was less frequent in cases of mitral annular calcification (0% vs 42%; P = 0.04) and left atrial enlargement (17% vs 65%; P = 0.03). Logistic regression analysis revealed negative predictors for MR improvement were mitral annular calcification (P = 0.04) and larger aortic annulus diastolic diameter (P = 0.05). Conclusion: Structural factors such as aortic annular size, mitral annular calcification and valve morphology may impact MR following AVR and should be investigated further as potential targets of surgical therapy.
The presence of mitral regurgitation (MR) is common in patients undergoing surgical aortic valve replacement (AVR) for aortic stenosis (AS), with reported incidence ranging from 10% to as high as 70% [
A retrospective review of patients undergoing AVR for AS at a single center from August 2010 to November 2013 was performed. Patients were evaluated by the heart team in a multidisciplinary valve clinic. Exclusion criteria were cases of degenerative MR or severe functional MR, as well as those undergoing concomitant aortic root reconstruction or AVR for aortic insufficiency. The in-house Institutional Review Board approved the review and informed consent was waived.
Carpentier-Edwards Magna Ease pericardial valves (Edwards Lifesciences, Irvine, CA) were implanted in all cases with pledgeted horizontal mattress suture technique. All patients received pre-operative and post-operative trans-thoracic echocardiographic (TTE) evaluations of MR by either of two attending cardiologists. Preoperative cardiac magnetic resonance imaging (CMR) was used to measure the aortic valve annulus in all patients.
Univariate analyses of factors associated with MR were performed. Continuous variables were normally distributed and therefore student t test was applied. Proportions were analyzed using x2 tests. Evaluation of MR improvement included only patients with preoperative MR. Evaluation of MR worsening included all patients in the cohort. Multivariable logistic regression analyses were applied using MR improvement and MR worsening as dependent variables.
Forty-four patients underwent AVR during the 3-year period, and met criteria for inclusion. Of these, 36 (81.8%) had some degree of pre-operative MR. Moderate MR was found in 2 cases (4.5%), mild-to-moderate in 4 (9.1%), mild in 20 (45.5%) and trace in 10 (22.7%) (
Patients with pre-operative MR were somewhat older (69.9 years ± 10 versus 61.0 ± 8; P = 0.02). Aortic annula measured by preoperative CMR during diastole were significantly smaller (22.8 mm ± 2 versus 24.6 ± 3;
MR severity | Pre-AVR (N = 44) | Post-AVR (N = 44) | % Improved | % Worsened |
---|---|---|---|---|
Moderate | 4.5% (2) | 0% | 100% | 0% |
Mild-moderate | 9.1% (4) | 4.5% (2) | 50% | 0% |
Mild | 45.5% (20) | 31.8% (14) | 30% | 0% |
Trace | 22.7% (10) | 54.5% (24) | 0% | 10% |
None | 18.2% (8) | 2.3% (1) | - | 62.5% |
Total MR | 81.8% (36) | 90.9% (40) | 44.4% | 2.8% |
MR: mitral regurgitation; AVR: aortic valve replacement.
P = 0.05) than those without MR, and this was nearly significant by systolic measurements (24.1 ± 2 versus 25.8 ± 3; P = 0.07). Incidence of mitral annular calcification (MAC) and left atrial enlargement (LAE) were much greater in patients with MR (P = 0.005 and 0.002, respectively) (
Among patients with pre-operative MR, cases of moderate and mild-to-moderate severity were more likely to improve compared with mild and trace (31.2% versus 5%; P = 0.04) (
Worsening of MR on post-operative TTE was found in 13.6% of the total 44 AVR cases, of which 5 had no MR identified pre-operatively. These patients had significantly more cases of bicuspid aortic valves (83.3% versus 23.7%; P = 0.004) and significantly larger average aortic annulus diameters as measured by CMR in systole (26.7 ± 3 versus 24.1 ± 2; P = 0.007), in diastole (25.6 ± 2 versus 22.8 ± 2; P = 0.003) and corroborated by larger average intra-operative valve sizing (24.0 ± 1 versus 22.8 ± 1; P = 0.03) (
Multivariable logistic regression analysis of MR improvement found the presence of MAC to be a negative predictor (P = 0.04) when controlling for aortic valve morphology, atrial fibrillation, or preoperative MR severity. In addition, for each millimeter increase in aortic annulus diameter during diastole, the likelihood of MR improvement decreased by 52% (P = 0.05). Logistic regression analysis did not identify independent predictors of MR worsening after controlling for the same variables.
MR (N = 36) | No MR (N = 8) | P-value | |
---|---|---|---|
Age (years) | 69.9 ± 10 | 61.0 ± 8 | 0.02 |
Diabetes | 61.1% (22) | 25.0% (2) | 0.06 |
BMI | 30.4 ± 6 | 32.8 ± 8 | 0.37 |
Hypertension | 86.1% (31) | 100% (8) | 0.26 |
ESRD | 2.8% (1) | 0% | 0.63 |
LVEF < 55% | 12.5% (1) | 27.8% (10) | 0.38 |
Current smoking | 37.5 (3) | 13.9% (5) | 0.11 |
MAC | 44.4% (16) | 0% | 0.005 |
Bicuspid | 22.2% (8) | 75.0% (6) | 0.004 |
AVA | 0.74 ± 0.1 | 0.75 ± 0.1 | 0.77 |
AV mean gradient | 44.2 ± 13 | 53.6 ± 24 | 0.13 |
AoA systolic diameter | 24.1 ± 2 | 25.8 ± 3 | 0.07 |
AoA diastolic diameter | 22.8 ± 2 | 24.6 ± 3 | 0.05 |
AVR prosthetic size | 22.9 ± 1 | 23.5 ± 1 | 0.20 |
LAE | 66.7% (24) | 10% (1) | 0.002 |
Atrial fibrillation | 14.3% (5) | 0% | 0.26 |
Maze procedure | 11.1% (4) | 0% | 0.32 |
CABG | 36.1% (13) | 50.0% | 0.47 |
Proportions expressed as %. Continuous variables expressed and mean ± stdev. MR: mitral regurgitation; BMI: body mass index; ESRD: end stage renal disease; LVEF: left ventricular ejection fraction; MAC: mitral annular calcification; AVA: aortic valve area; AV: aortic valve; AoA: aortic valve annulus; AVR: aortic valve replacement; LAE: left atrial enlargement; CABG: coronary artery bypass grafting.
MR Improvement (N = 16) | No MR Improvement (N = 20) | P-value | |
---|---|---|---|
Age (years) | 68.8 ± 9 | 70.7 ± 10 | 0.56 |
Diabetes | 62.5% (10) | 60.0% (12) | 0.88 |
BMI | 30.4 ± 6 | 30.4 ± 7 | 1.00 |
Hypertension | 87.5% (14) | 85.0% (17) | 0.83 |
ESRD | 0% | 5.0% (1) | 0.36 |
LVEF < 55% | 32.1% (5) | 25.0% (5) | 0.68 |
Current smoking | 12.5% (2) | 15.0% (3) | 0.83 |
MR worse than mild | 31.2% (5) | 5.0% (1) | 0.04 |
MAC | 31.2% (5) | 55.0% (11) | 0.20 |
Bicuspid | 18.8% (3) | 25.0% (5) | 0.65 |
AVA | 0.73 ± 0.1 | 0.75 ± 0.2 | 0.67 |
AV mean gradient | 48.8 ± 15 | 40.8 ± 10 | 0.07 |
AoA systolic diameter | 23.6 ± 2 | 23.1 ± 1 | 0.14 |
AoA diastolic diameter | 23.6 ± 2 | 23.3 ± 2 | 0.07 |
AVR prosthetic size | 22.6 ± 1 | 23.1 ± 1 | 0.23 |
LAE | 68.8% (11) | 65.0% (13) | 0.60 |
Atrial fibrillation | 18.8% (3) | 10.0% (2) | 0.40 |
Maze procedure | 12.5% (2) | 10.0% (2) | 0.81 |
CABG | 43.8% (7) | 30.0% (6) | 0.39 |
Proportions expressed as %. Continuous variables expressed and mean ± stdev. MR: mitral regurgitation; BMI: body mass index; ESRD: end stage renal disease; LVEF: left ventricular ejection fraction; MAC: mitral annular calcification; AVA: aortic valve area; AV: aortic valve; AoA: aortic valve annulus; AVR: aortic valve replacement; LAE: left atrial enlargement; CABG: coronary artery bypass grafting.
MR Worsening (N = 6) | No MR Worsening (N = 38) | P-value | |
---|---|---|---|
Age (years) | 60.7 ± 6 | 69.5 ± 10 | 0.04 |
Diabetes | 33.3% (2) | 57.9% (22) | 0.26 |
BMI | 32.0 ± 5 | 30.6 ± 7 | 0.64 |
Hypertension | 100% (6) | 86.8% (33) | 0.35 |
ESRD | 0% | 2.6% (1) | 0.69 |
LVEF < 55% | 33.3% (2) | 23.7% (9) | 0.61 |
Current smoking | 33.3% (2) | 15.8% (6) | 0.30 |
MR worse than mild | 0% | 15.8% (6) | 0.30 |
MAC | 0% | 42.1% (16) | 0.04 |
Bicuspid AV | 83.3% (5) | 23.7% (9) | 0.004 |
AVA | 0.78 ± 0.1 | 0.74 ± 0.1 | 0.51 |
AV mean gradient | 58.1 ± 26 | 44.0 ± 13 | 0.04 |
AoA systolic diameter | 26.7 ± 3 | 24.1 ± 2 | 0.007 |
AoA diastolic diameter | 25.6 ± 2 | 22.8 ± 2 | 0.003 |
AVR prosthetic size | 24.0 ± 1 | 22.8 ± 1 | 0.03 |
LAE | 16.7% (1) | 64.9% (24) | 0.03 |
Atrial fibrillation | 0% | 13.2% (5) | 0.34 |
Maze procedure | 0% | 10.5% (4) | 0.41 |
CABG | 50.0% (3) | 36.8% (14) | 0.54 |
Proportions expressed as %. Continuous variables expressed and mean ± stdev. MR: mitral regurgitation; BMI: body mass index; ESRD: end stage renal disease; LVEF: left ventricular ejection fraction; MAC: mitral annular calcification; AVA: aortic valve area; AV: aortic valve; AoA: aortic valve annulus; AVR: aortic valve replacement; LAE: left atrial enlargement; CABG: coronary artery bypass grafting.
A growing body of literature has identified reproducible structural changes in the MA following AVR. Improved imaging modalities, particularly 3-D trans-esophageal echocardiography (TEE), have enhanced our understanding of mitral-aortic coupling in this setting [
The implications of the MA parameter effects are often unclear, representing limitations in our understanding of the anatomic relationships. A review by Waisbren et al. of 227 patients undergoing AVR for AS found a greater improvement in MR when it was more severe pre-operatively [
Some have labelled the improvement of MR following AVR a “functional mitral annuloplasty” [
The finding of worse MR after AVR in our patients with bicuspid aortic valves suggests that variation in flexibility of the aortic annulus affects the mitral valve by altering tension across the aortic-mitral curtain. The absence of MAC in patients with MR worsening adds to previous discussions in the literature about AVR prosthesis compression of the mitral annulus. Although an inflexible prosthetic AV stent may reduce anterolateral dimension of the mitral annulus to increase mitral coaptation in some patients, it is conceivable that MAC shields the mitral annulus against this compression through its own rigidity. Interestingly, MAC was also a negative predictor of MR improvement, reinforcing the hypothesis that MAC stabilizes the mitral annulus.
That fact that larger aortic annula in our patients conferred greater risk of MR worsening is also congruent with the understanding that forces acting across the aortic-mitral curtain can affect mitral valve coaptation. Distortion conferred on the MA from the AV prosthesis may enhance alignment at some optimal distance, but when delivered to a larger extent could surpass that point of equilibrium creating worsening of MR.
Although not statistically significant, the percentage of patients with atrial fibrillation that experienced MR improvement was greater than those without improvement, and none had MR worsening. Of the 5 patients with pre-operative atrial fibrillation, 4 underwent Maze procedures via epicardial radiofrequency ablation. Atrial functional MR has been supported as a mechanism of MR improvement in other settings and may have contributed in some of our patients [
Several important aspects of our study limit its interpretation. Small sample size decreases statistical power, and indeed numerical trends in valve sizes and atrial fibrillation remained indeterminate. The cohort of preoperative MR patient also consisted of a large proportion of mild and trace MR. Although moderate MR carries more clinical influence pertaining to questions of survival and operative decision-making, milder cases of MR likely hold value in defining immediate structural effects on aortic-mitral coupling. Ultimately a prospective study that includes medium and long-term outcomes of MR and survival would elucidate the importance of early post- operative echocardiographic findings and their impact on ventricular remodeling.
The structural coupling of the aortic and mitral valve is a relationship that undergoes measurable changes following AVR for AS. Though this issue is made complex by functional changes due to decrease in trans-aortic pressure gradient and subsequent ventricular remodeling, the structural effects must be clearly defined in order to understand the impact on mitral valve function. Enhanced understanding has great potential to usher valve design innovation and individualized surgical decision-making that will improve clinical outcomes.
The authors have not received financial support for this research, and have no conflicts of interest.
Conor F.Hynes,Dominic A.Emerson,Michael D.Greenberg,Federico E.Mordini,Gregory D.Trachiotis,11, (2016) The Structural Impact of Aortic Valve Replacement on Mitral Regurgitation. World Journal of Cardiovascular Surgery,06,19-24. doi: 10.4236/wjcs.2016.62004