Changes in mitral valve geometry in patients with significant aortic regurgitation (AR) have not been evaluated. The aim of the present study was to assess the prevalence of significant secondary mitral regurgitation (MR; grade ≥ 2) and the geometric characteristics of the mitral valve in patients with moderate and severe AR (grade ≥ 2) undergoing aortic valve and root surgery.
One-hundred twenty patients (mean age, 54 ± 15 years; 65% men) with AR grade ≥ 2 undergoing aortic valve and root surgery were retrospectively evaluated. The presence of MR grade ≥ 2 and geometry of the mitral valve were assessed on preoperative transthoracic echocardiography. Left ventricular (LV) dimensions and mitral valve geometry were compared between patients with MR grade ≥ 2 and patients without.
MR grade ≥ 2 was present in 28 patients (23%). Patients with MR grade ≥ 2 had higher European System for Cardiac Operative Risk Evaluation II scores and more often used β-blockers and diuretics than their counterparts. Patients with MR grade ≥ 2 had larger tenting areas (mean, 1.59 ± 0.79 vs 1.25 ± 0.41 cm 2 ; P = .003), larger inter–papillary muscle distances (mean, 28.4 ± 9.5 vs 24.8 ± 5.2 mm; P = .014), larger left atria (mean, 40.9 ± 13.7 vs 32.0 ± 12.2 mL/m 2 ; P = .002), and lower LV ejection fractions (mean, 47.3 ± 12.2% vs 54.3 ± 9.3%; P = .002) as compared to patients with MR grade < 2. However, there were no differences in indexed LV volumes. On multivariate logistic regression analysis, LV ejection fraction (odds ratio, 0.94; 95% confidence interval, 0.89–0.99; P = .018) and indexed left atrial volume (odds ratio, 1.05; 95% confidence interval, 1.01–1.10; P = .019) remained independently associated with MR grade ≥ 2 after correcting for tenting area and inter–papillary muscle distance.
Among patients with AR grade ≥ 2 undergoing aortic valve and root surgery, the prevalence of MR grade ≥ 2 was 23%. Lower LV ejection fraction and larger left atrial volume were independently associated with MR grade ≥ 2.
MR was present in 23% of patients with AR.
Mitral valve geometry was assessed in patients with and without MR.
Lower LVEF was associated with significant MR.
The prevalence of secondary mitral regurgitation (MR) in patients with significant aortic regurgitation (AR) ranges between 6% and 45%. The left ventricular (LV) pressure and volume overload caused by significant AR leads to LV dilation, with subsequent changes in papillary muscle position and tethering of the mitral leaflets, which may cause coaptation failure and regurgitation. The prognostic implications of concomitant secondary MR in patients with significant AR are not benign, and it has been shown that mitral valve surgery in addition to aortic valve surgery is associated with better prognosis. However, it remains unclear why some patients with significant AR have concomitant significant secondary MR while other patients do not show MR.
A pioneer study using three-dimensional transthoracic echocardiography suggested that patients with significant AR show significantly larger total mitral leaflet area compared with patients without AR, which may reflect mitral leaflet remodeling to prevent failure of mitral leaflet coaptation. However, changes in mitral valve geometry, including the subvalvular apparatus in patients with significant AR, have not been evaluated. In addition, the effects of confounding factors such as concomitant ischemic heart disease on LV remodeling and the development of secondary MR in this specific subpopulation have not been elucidated. Therefore, the aims of the present study were to investigate the prevalence of significant MR, evaluate changes in mitral valve geometry, and investigate the associates of MR in patients with significant AR.
Preoperative two-dimensional echocardiograms from 166 patients with AR grade ≥ 2 referred for valve-sparing aortic root reconstruction to the Cardio-Thoracic Surgery Department of Leiden University Medical Center from 2001 to 2014 were evaluated. Patients with acute endocarditis, connective tissue disease, insufficient image quality, organic MR, or mitral stenosis were excluded ( Figure 1 ).
Clinical characteristics were prospectively collected in the departmental cardiology information system (EPD-Vision; Leiden University Medical Center, Leiden, The Netherlands) and retrospectively analyzed. Mitral valve geometry, MR grade, AR grade, and LV volumes and function were analyzed. Mitral valve geometry was compared between patients with moderate or severe secondary MR and patients without.
The institutional review board approved this retrospective analysis of clinically acquired data and waived the need for patient written informed consent.
Two-Dimensional Transthoracic Echocardiography
Transthoracic echocardiography was performed preoperatively using commercially available ultrasound systems (System Five, Vivid 7, and Vivid E9; GE Vingmed Ultrasound AS, Horten, Norway) equipped with 3.5-MHz or M5S transducers. Parasternal, apical, subcostal, and suprasternal views were obtained at rest with patients in the left decubitus position. Two-dimensional and Doppler data were acquired according to current recommendations. The echocardiographic data were digitally stored in cine-loop format, and data were retrospectively analyzed using commercially available software (EchoPAC version 112.0.1; GE Vingmed Ultrasound AS).
AR grade was assessed using a multiparametric approach including the measurement of the jet width relative to the LV outflow tract (LVOT) width and the vena contracta in the parasternal and apical views. AR was graded as grade 2 (mild to moderate; jet width/LVOT width ratio of 0.25–0.45 and/or vena contracta of 3.0–4.5 mm), grade 3 (moderate to severe; jet width/LVOT width ratio of 0.46–0.64 and/or vena contracta of 4.6–5.9 mm), or grade 4 (severe; jet width/LVOT width ratio ≥ 0.65 and/or vena contracta ≥ 6.0 mm). The severity of secondary MR was quantitatively determined by the proximal isovelocity surface area method or by measuring the vena contracta in the parasternal long-axis view, according to current recommendations. MR was graded as absent when there was no regurgitant jet. Among patients with regurgitant jets, the proximal isovelocity surface area method could be performed in 45 patients. In the remaining 33 patients, vena contracta measurement in the parasternal long-axis view was used to classify MR. Secondary MR was defined as mild (regurgitant volume < 15 mL or vena contracta of 0.1 to 2.9 mm), moderate (regurgitant volume of 15 to 29 mL or vena contracta of 3 to 6.9 mm), or severe (regurgitant volume ≥ 30 mL or vena contracta ≥ 7 mm).
Mitral valve geometry was assessed in the parasternal long-axis view ( Figure 2 ). Retrospectively, the images were zoomed in on the mitral valve. The measurements were performed by two independent observers, and values were averaged. The length of coaptation between the anterior and posterior mitral leaflets (coaptation length), the distance between the annular plane and the coaptation point (coaptation height), and the area enclosed between the annular line and the mitral leaflets (tenting area) were measured in mid-systole. Anterior and posterior mitral leaflet length was measured in mid-diastole. The parasternal short-axis view was used to measure the end-diastolic inter–papillary muscle distance. The mitral annulus was measured at end-systole in the apical views. The anterior-posterior diameter and intercommissural diameter were obtained from the apical four- and two-chamber views, respectively.
Left atrial volume, LV end-diastolic volume, and LV end-systolic volume were measured in the apical two- and four-chamber views and indexed to body surface area (left atrial volume index [LAVi], LV end-diastolic volume index, and LV end-systolic volume index [LVESVi]). Sphericity index was calculated by dividing the length by the width of the left ventricle in the apical four-chamber view, as previously described. LV ejection fraction (LVEF) was calculated according to Simpson’s biplane method.
After medial sternotomy, cardiopulmonary bypass was set through cannulation of the distal ascending aorta or the subclavian or femoral artery (in patients with ascending aortic pathology). The aorta was incised at the level of the pulmonary artery and resected until the sinotubular junction.
Intraoperatively, the surgeon decided whether valve-sparing aortic root reconstruction was feasible. In these patients, either the sinotubular junction was restored using a vascular graft or the native sinuses of Valsalva were resected, a graft was implanted using the reimplantation technique (modified David procedure), or the remodeling technique (Yacoub procedure) and the coronary buttons were reimplanted. Otherwise, aortic valve and root replacement using the Medtronic Freestyle stentless bioprosthesis (Medtronic, Minneapolis, MN) was performed. In these patients, the coronary buttons were mobilized, and the aortic root and valve were completely excised. The bioprosthesis was then implanted, usually with 120° clockwise rotation, with interrupted sutures at one plane at the level of the nadir of the sinus. Thereafter, the coronary buttons were reattached to the bioprosthesis.
If secondary MR was present, concomitant mitral valve surgery was performed at the discretion of the surgeon. In all patients in whom concomitant mitral valve surgery was performed, restrictive ring annuloplasty was used to repair the mitral valve. No mitral valve replacements were performed.
All data analyses were performed using SPSS version 20.0 (IBM, Armonk, NY). Continuous variables are reported as mean ± SD or as medians and interquartile ranges, as appropriate. Categorical variables are reported as counts and percentages. Patients with no or mild MR (grade < 2) were compared with patients with moderate or severe MR (grade ≥ 2). Continuous and categorical variables were compared by using the Student t test (or the Mann-Whitney U test for variables not normally distributed) and the χ 2 test, respectively. Mitral valve geometric changes were compared between patients with normal left ventricles (LVESVi < 31 mL/m 2 ) and patients with dilated left ventricles (LVESVi ≥ 31 mL/m 2 ). Multivariate logistic regression analysis was performed to investigate the independent associates of significant (moderate or severe) secondary MR. All echocardiographic variables with P values < .05 on univariate logistic regression analysis were included in the multivariate model. The odds ratio and 95% confidence interval were calculated. All statistical tests were two sided. P values < .05 were considered to indicate statistical significance. Interobserver and intraobserver variability of mitral valve geometry measurements was evaluated using Bland-Altman analysis in 40 randomly selected patients. Furthermore, the coefficients of variation were calculated for coaptation length, coaptation height, and tenting area.
A total of 120 patients (mean age, 54 ± 15 years; 65% men) were included in the present analysis. AR was grade 2 in 52 patients (43%), grade 3 in 43 (36%), and grade 4 in 25 (21%). Forty-two patients (35%) did not have MR. Mild, moderate, and severe MR were observed in 50 (42%), 25 (21%), and three (2%) patients, respectively. The prevalence of significant secondary MR (moderate and severe) was 23%. Patients were divided into two groups according to the presence and severity of secondary MR: patients without significant secondary MR ( n = 92) were compared with those with moderate or severe secondary MR ( n = 28). Table 1 shows the differences in baseline clinical characteristics between groups.
|Variable||Nonsignificant secondary MR||Significant secondary MR||P|
|( n = 92)||( n = 28)|
|Age (y)||53.3 ± 15.2||57.7 ± 13.7||.174|
|Men||58 (63%)||20 (71%)||.556|
|Smoking||25 (27%)||7 (25%)||.989|
|Diabetes||3 (3%)||2 (7%)||.719|
|Hypertension||45 (49%)||18 (64%)||.226|
|Dyslipidemia||20 (22%)||3 (11%)||.252|
|NYHA functional class||1.000|
|I and II||70 (76%)||21 (75%)|
|III and IV||22 (24%)||7 (25%)|
|Creatinine clearance (mL/min)||103 ± 37||85 ± 29||.023|
|Coronary artery disease||16 (17%)||6 (21%)||.838|
|Previous myocardial infarction||.435|
|Anterior||1 (1%)||1 (4%)|
|Nonanterior||3 (3%)||2 (7%)|
|ACE inhibitor or angiotensin receptor blocker||45 (49%)||19 (68%)||.123|
|β-blocker||31 (34%)||18 (64%)||.008|
|Calcium channel antagonist||17 (19%)||2 (2%)||.253|
|Diuretics||25 (27%)||15 (54%)||.018|
|Grade 2||39 (42%)||13 (46%)|
|Grade 3||36 (39%)||7 (25%)|
|Grade 4||17 (19%)||8 (29%)|
|EuroSCORE II (%)||2.4 (1.6–4.5)||3.6 (2.5–7.8)||.003|
|Aortic valve/root technique||.048|
|Repair||51 (55%)||22 (79%)|
|Replacement||41 (45%)||6 (21%)|
|CABG||19 (21%)||6 (21%)||1.000|
|Mitral valve repair||2 (2%)||11 (39%)||<.001|
|Tricuspid valve repair||1 (1%)||9 (32%)||<.001|
Patients were comparable regarding age, gender, and comorbidities. Patients with significant secondary MR had a higher frequency of prior myocardial infarction than patients without MR; however, this difference was not statistically significant. In addition, the presence of cardiovascular risk factors and the need for coronary artery bypass grafting was not different between patients with and without MR. However, β-blockers and diuretics were more frequently used among patients with MR grade ≥ 2 compared with their counterparts.
Patients with moderate or severe secondary MR had higher European System for Cardiac Operative Risk Evaluation II scores (median, 3.6% [interquartile range, 2.5%–7.8%] vs 2.4% [interquartile range, 1.6%–4.5%]; P = .003) compared with their counterparts. Seventy-three patients (61%) underwent valve-sparing aortic root reconstruction. The remaining 47 patients (39%) were considered ineligible for repair during surgery and underwent aortic valve and root replacement using the Medtronic Freestyle stentless bioprosthesis.
Concomitant coronary artery bypass grafting was performed in 25 patients (21%). Concomitant mitral valve surgery with restrictive ring mitral annuloplasty was performed in 13 patients (11%). Concomitant tricuspid valve surgery (annuloplasty) was performed in 10 patients (8%).
Echocardiographic Measurements Associated with Preoperative Secondary MR
The preoperative echocardiographic data are presented in Table 2 . LV volumes and mitral valve geometric measurements in the parasternal long-axis view were available in all 120 patients, whereas inter–papillary muscle distance and LAVi were available in 108 and 119 patients, respectively. Coaptation length, coaptation height, and the lengths of the anterior and posterior leaflets were comparable in both groups. Patients with moderate or severe secondary MR had larger tenting areas (1.59 ± 0.79 vs 1.25 ± 0.41 cm 2 , P = .003) and larger inter–papillary muscle distances (28.4 ± 9.5 vs 24.8 ± 5.2 mm, P = .014) compared with those without significant secondary MR. There was a tendency toward larger mitral annular diameters among patients with MR grade ≥ 2. LV end-diastolic volume index was comparable between patients with and without secondary MR, whereas LVESVi was slightly larger (nonsignificant) in patients with moderate or severe secondary MR. Consequently, the LVEF was significantly lower in patients with moderate or severe secondary MR (47.3 ± 12.2% vs 54.3 ± 9.3%, P = .002).
|Variable||Non-significant secondary MR||Significant secondary MR||P|
|( n = 92)||( n = 28)|
|Anterior leaflet length (mm)||24.6 ± 4.1||24.6 ± 4.1||.970|
|Posterior leaflet length (mm)||18.3 ± 3.2||18.9 ± 3.6||.383|
|Coaptation length (mm)||7.8 ± 1.7||7.3 ± 1.9||.273|
|Coaptation height (mm)||8.0 ± 2.3||8.5 ± 2.6||.287|
|Tenting area (cm 2 )||1.25 ± 0.41||1.59 ± 0.79||.003|
|Inter–papillary muscle distance (mm)||24.8 ± 5.2||28.4 ± 9.5||.014|
|Mitral annular AP diameter (mm)||31.0 ± 4.9||33.1 ± 6.0||.068|
|Mitral annular intercommissural diameter (mm)||31.4 ± 5.2||33.5 ± 5.6||.068|
|LAVi (mL/m 2 )||32.0 ± 12.2||40.9 ± 13.7||.002|
|LVEDVi (mL/m 2 )||77.4 ± 27.9||79.6 ± 28.9||.715|
|LVESVi (mL/m 2 )||36.1 ± 17.5||42.8 ± 23.9||.104|
|Sphericity index||1.59 ± 0.27||1.59 ± 0.25||.949|
|LVEF (%)||54.3 ± 9.3||47.3 ± 12.2||.002|