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Abstract

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OBJECTIVES

The goal of this study was to quantify the mitral valve (MV) annulus, the MV shape and the anatomical MV orifice area throughout the cardiac cycle using 4-dimensional MV analysis software in patients with primary mitral regurgitation (PMR) and secondary mitral regurgitation (SMR) in comparison to a healthy control group.

METHODS

Three-dimensional transoesophageal echocardiograms of the MV were acquired for 29 patients with PMR, for 28 patients with SMR and for 18 healthy control subjects. The MV was quantified with regards to anterior-posterior and lateromedial diameter, annular area and circumference, intertrigonal (IT) distance, annular sphericity index, annular height to commissural width ration, and anatomical MV orifice area throughout the cardiac cycle using 3-dimensional transoesophageal echocardiography-based 4-dimensional MV advanced analysis software.

RESULTS

Normal annulus dynamics display a systolic enlargement followed by an early-diastolic plateau phase and a late-diastolic contraction. The IT distance showed a linear association with the anterior-posterior diameter (= 1.11 × IT distance) and lateromedial diameter (= 1.44 × IT distance) in the control subjects. Mitral regurgitation is associated with a less dynamic, planar and dilated annulus with small variations between PMR and SMR. The IT distance was less affected by mitral regurgitation compared to the control subjects.

CONCLUSIONS

The novel 4-dimensional MV analysis allows new insights into the dynamic MV geometry in patients with PMR and SMR compared to the control subjects. The IT distance may be used to predict annuloplasty ring sizing.

Mitral regurgitation , Mitral valve repair , 3-Dimensional echocardiography , Mitral valve geometry

INTRODUCTION

The mitral valve (MV) is a complex asymmetrical dynamic structure consisting of valvular leaflets, annulus and subvalvular apparatus with tendinous chords and papillary muscles [1–3]. The exact, synchronized interaction of the different MV structures with the left atrium and the left ventricle leads to a physiological closing during systole and opening during diastole. Herewith are the physiological and pathophysiological characteristics of the MV and their dynamic changes throughout the cardiac cycle from the most important area of interest, particularly with regards to the surgical or interventional treatment of mitral regurgitation (MR). However, the depth of medical knowledge about the dynamic changes in the MV annulus, the shape and the anatomical MV orifice area (AMVOA) throughout the cardiac cycle in patients with MR is limited.

Pioneering echocardiographic and computer tomographic (CT) work with 3-dimensional (3D) reconstruction defined the mitral annulus as ‘saddle shaped’ with dynamic changes throughout the cardiac cycle [1, 4–7]. The presence of MR is associated with a dilatated and more planar mitral annulus, which leads to a loss of MV competency and progression of MR [1, 8].

Recently, the feasibility and reproducibility of the novel model-based 3D MV quantification have been demonstrated using 3D transoesophageal echocardiography (3D-TOE) [1, 4, 5, 8–11]. Advances in 3D-TOE-based MV analysis software allows simultaneous quantification of the MV annulus, shape and AMVOA throughout the cardiac cycle [4-dimensional (4D) MV analysis] [12–14]. However, only limited data on the clinical utility of 3D-TOE-based 4D MV analysis exist.

The aims of this study were to analyse the MV geometry using 4D MV analysis software in patients with primary MR (PMR) and secondary MR (SMR) in comparison with a healthy control group as well as to quantify the geometrically differences of MV between PMR and SMR. Special focus was given to (i) quantification of annular dimensions, shape and AMVOA, (ii) their dynamic changes throughout the cardiac cycle and (iii) determination of a reliable predictor for annuloplasty ring size to be used in surgical MV repair.

MATERIALS AND METHODS

Study population

Three study groups were identified: 2 groups with MR and 1 control group without MR. Patients with MR were divided into 2 groups based on the MR mechanism: the PMR group and the SMR group. Between April 2013 and November 2016, we prospectively included patients undergoing clinically indicated TOE (PMR and SMR groups) or with a written consent form (control group) at our centre. Inclusion criteria for the 2 MR groups were as follows: (i) isolated MR; (ii) no mitral stenosis; (iii) no clinically relevant other heart valve diseases (regurgitation or stenosis > mild). Inclusion criteria for the control group included no clinically relevant heart valve diseases (regurgitation or stenosis > mild). Exclusion criteria for all groups included (i) poor visualization of MV with 3D-TOE; (ii) poor spatial and temporal resolution of MV in 3D-TOE (frame rate ≤ 8 frames/cardiac cycle, stitching artefacts); and (iii) prior heart valve interventions or surgery. The study was approved by the ethics committee of the medical faculty of Leipzig University. All patients provided written informed consent before inclusion in the study.

Data acquisition using transoesophageal echocardiography

3D-TOE data sets from the MV were acquired according to recommendations of the American Society of Echocardiography and the European Association of Echocardiography by certificated echocardiographers under stable haemodynamic conditions with the patients in the supine position [15, 16]. 3D-TOE imaging was performed using an iE33 ultrasound system equipped with an X7-2t transducer (Philips GmbH, Hamburg, Germany) or an Acuson SC2000 ultrasound system equipped with a Z6Ms transducer (Siemens Healthineers GmbH, Erlangen, Germany).

4-Dimensonal assessment of the mitral valve

For 4D MV quantification, we used the Auto Valve advanced analysis software (Siemens Healthineers, Erlangen, Germany) as previously published (Fig. 1) [12–14, 17, 18]. Accuracy, reproducibility and reliability of the 4D MV analysis software was investigated by the authors in a previous study [13]. All selected 3D-TOE data sets were screened for suitability for 4D MV quantification. We defined the beginning of systole as the frame before the opening of the aortic valve and the end of diastole as the frame showing complete MV closure. Relevant MV variables such as the AMVOA, anterior-posterior (AP) diameter, lateral-medial (LM) diameter, intertrigonal (IT) distance, annular circumference, annular area, annular sphericity index (ASI) and annular height to commissural width ratio (AHCWR) were measured throughout the cardiac cycle. The AMVOA was defined as the MV orifice projected into its least square plane. The ASI refers to the ratio between the AP and the LM diameters. Quantification of annular dimensions are given in Fig. 2. A schematic overview about time-adjusted MV quantification is given in Fig 3.

Mitral valve (MV) assessment by 4-dimensional MV analysis. (A) Detection of the position of the MV in the 3-dimensional transoesophageal echocardiography data set with a computed MV model throughout the cardiac cycle. (B) Analysis software allows manual adjustments if indicated. (C) Quantification of annular parameters throughout the cardiac cycle. Ao: aorta; LA: left atrium; LV: left ventricle.
Figure 1:

Mitral valve (MV) assessment by 4-dimensional MV analysis. (A) Detection of the position of the MV in the 3-dimensional transoesophageal echocardiography data set with a computed MV model throughout the cardiac cycle. (B) Analysis software allows manual adjustments if indicated. (C) Quantification of annular parameters throughout the cardiac cycle. Ao: aorta; LA: left atrium; LV: left ventricle.

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Representation of the quantification of the geometry of the mitral valve throughout the CC and the definition of 6 specific times during the CC using examples from the AMVOA. AMVOA: anatomic mitral valve orifice area; CC: cardiac cycle; PMR: primary mitral regurgitation; SMR: secondary mitral regurgitation.
Figure 2:

Representation of the quantification of the geometry of the mitral valve throughout the CC and the definition of 6 specific times during the CC using examples from the AMVOA. AMVOA: anatomic mitral valve orifice area; CC: cardiac cycle; PMR: primary mitral regurgitation; SMR: secondary mitral regurgitation.

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Intercommissural (A) and transvalvular (B) views of the mitral valve annulus with quantification of annular dimensions. (C) Calculation of the AHCWR and ASI. AH: annular height; AHCWR: annular height to commissural width ratio; AP: anterior-posterior; ASI: annular sphericity index; CW: commissural width; IT: intertrigonal distance; LM: lateral-medial; LT: lateral trigone; MT: medial trigone.
Figure 3:

Intercommissural (A) and transvalvular (B) views of the mitral valve annulus with quantification of annular dimensions. (C) Calculation of the AHCWR and ASI. AH: annular height; AHCWR: annular height to commissural width ratio; AP: anterior-posterior; ASI: annular sphericity index; CW: commissural width; IT: intertrigonal distance; LM: lateral-medial; LT: lateral trigone; MT: medial trigone.

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Statistical analyses

Data were tested for normal distribution by the Kolmogorov–Smirnov or χ2 normality test. Normally distributed data are expressed as mean ± standard deviation and categorical data, as proportions and percentage. An unpaired t-test was used to evaluate for statistically significant differences between the control group and the PMR group, the control group and the SMR group and the PMR group and the SMR group. Linear regression analysis and scatterplots were used to investigate linear relationships of different annular dimensions in the control group.

The geometrical relationship of the AP and LM diameters and the IT distance is calculated using the following formula: AP diametert = Xt * IT distancet. The coefficient Xt is calculated by dividing the mean AP diameter by the mean IT distance for time point t. The same algorithm is used for the description of the geometrical relationship between the LM diameter and the IT distance (LM diametert = Yt * IT distance; Yt = mean LM diametert/mean IT distancet).

A value of P-value <0.05 was considered statistically significant. Analyses were performed using IBM SPSS Statistics Version 21 (SPSS Inc., Chicago, IL, USA).

RESULTS

Patient population

Between January 2013 and December 2016, 105 patients underwent prospectively 3D-TOE. Thirty patients were not included due to exclusion criteria. Seventy-five patients were included in this study: 18 patients in the control group, 29 patients in the PMR group and 28 patients in the SMR group. Patient characteristics are presented in Table 1.

Table 1:
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Patient characteristics

VariablesControl subjects (n = 18)PMR (n = 29)P-valueaSMR (n = 28)P-valueb
Clinical
 Age (years), mean ± SD67 ± 1063 ± 200.1477 ± 80.002c
 Female gender, n (%)5 (28)10 (35)0.6310 (36)0.75
 Body mass index (kg/m2), mean ± SD30 ± 525 ± 30.00128 ± 50.10c
 Hypertension, n (%)17 (94)17 (59)0.0126 (93)1.00c
 Diabetes, n (%)7 (39)1 (4)0.00213 (46)0.76c
 Hyperlipidaemia, n (%)14 (78)8 (28)0.00117 (61)0.41c
 Atrial fibrillation, n (%)1 (6)17 (59)<0.00119 (68)<0.001
Echocardiography
 LV ejection fraction (%), mean ± SD50 ± 962 ± 120.00140 ± 160.02c
 MR grade, n (%)
  None/mild18 (100)<0.001<0.001
  Moderate6 (21)<0.0012 (7)<0.001
  Severe23 (79)<0.00126 (93)<0.001
 Vena contracta (mm), mean ± SD1 ± 27 ± 11<0.0018 ± 2<0.001
Status during echocardiography, mean ± SD
 Systolic blood pressure (mmHg)128 ± 15122 ± 140.14127 ± 220.82
 Diastolic blood pressure (mmHg)75 ± 972 ± 110.3473 ± 140.56
 Heart rate (min−1)76 ± 1179 ± 150.5778 ± 160.69
VariablesControl subjects (n = 18)PMR (n = 29)P-valueaSMR (n = 28)P-valueb
Clinical
 Age (years), mean ± SD67 ± 1063 ± 200.1477 ± 80.002c
 Female gender, n (%)5 (28)10 (35)0.6310 (36)0.75
 Body mass index (kg/m2), mean ± SD30 ± 525 ± 30.00128 ± 50.10c
 Hypertension, n (%)17 (94)17 (59)0.0126 (93)1.00c
 Diabetes, n (%)7 (39)1 (4)0.00213 (46)0.76c
 Hyperlipidaemia, n (%)14 (78)8 (28)0.00117 (61)0.41c
 Atrial fibrillation, n (%)1 (6)17 (59)<0.00119 (68)<0.001
Echocardiography
 LV ejection fraction (%), mean ± SD50 ± 962 ± 120.00140 ± 160.02c
 MR grade, n (%)
  None/mild18 (100)<0.001<0.001
  Moderate6 (21)<0.0012 (7)<0.001
  Severe23 (79)<0.00126 (93)<0.001
 Vena contracta (mm), mean ± SD1 ± 27 ± 11<0.0018 ± 2<0.001
Status during echocardiography, mean ± SD
 Systolic blood pressure (mmHg)128 ± 15122 ± 140.14127 ± 220.82
 Diastolic blood pressure (mmHg)75 ± 972 ± 110.3473 ± 140.56
 Heart rate (min−1)76 ± 1179 ± 150.5778 ± 160.69
a

Control versus PMR.

b

Control versus SMR.

c

P-value <0.05, PMR versus SMR.

LV: left ventricle; MR: mitral regurgitation; PMR: primary mitral regurgitation; SD: standard deviation; SMR: secondary mitral regurgitation.

Table 1:
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Patient characteristics

VariablesControl subjects (n = 18)PMR (n = 29)P-valueaSMR (n = 28)P-valueb
Clinical
 Age (years), mean ± SD67 ± 1063 ± 200.1477 ± 80.002c
 Female gender, n (%)5 (28)10 (35)0.6310 (36)0.75
 Body mass index (kg/m2), mean ± SD30 ± 525 ± 30.00128 ± 50.10c
 Hypertension, n (%)17 (94)17 (59)0.0126 (93)1.00c
 Diabetes, n (%)7 (39)1 (4)0.00213 (46)0.76c
 Hyperlipidaemia, n (%)14 (78)8 (28)0.00117 (61)0.41c
 Atrial fibrillation, n (%)1 (6)17 (59)<0.00119 (68)<0.001
Echocardiography
 LV ejection fraction (%), mean ± SD50 ± 962 ± 120.00140 ± 160.02c
 MR grade, n (%)
  None/mild18 (100)<0.001<0.001
  Moderate6 (21)<0.0012 (7)<0.001
  Severe23 (79)<0.00126 (93)<0.001
 Vena contracta (mm), mean ± SD1 ± 27 ± 11<0.0018 ± 2<0.001
Status during echocardiography, mean ± SD
 Systolic blood pressure (mmHg)128 ± 15122 ± 140.14127 ± 220.82
 Diastolic blood pressure (mmHg)75 ± 972 ± 110.3473 ± 140.56
 Heart rate (min−1)76 ± 1179 ± 150.5778 ± 160.69
VariablesControl subjects (n = 18)PMR (n = 29)P-valueaSMR (n = 28)P-valueb
Clinical
 Age (years), mean ± SD67 ± 1063 ± 200.1477 ± 80.002c
 Female gender, n (%)5 (28)10 (35)0.6310 (36)0.75
 Body mass index (kg/m2), mean ± SD30 ± 525 ± 30.00128 ± 50.10c
 Hypertension, n (%)17 (94)17 (59)0.0126 (93)1.00c
 Diabetes, n (%)7 (39)1 (4)0.00213 (46)0.76c
 Hyperlipidaemia, n (%)14 (78)8 (28)0.00117 (61)0.41c
 Atrial fibrillation, n (%)1 (6)17 (59)<0.00119 (68)<0.001
Echocardiography
 LV ejection fraction (%), mean ± SD50 ± 962 ± 120.00140 ± 160.02c
 MR grade, n (%)
  None/mild18 (100)<0.001<0.001
  Moderate6 (21)<0.0012 (7)<0.001
  Severe23 (79)<0.00126 (93)<0.001
 Vena contracta (mm), mean ± SD1 ± 27 ± 11<0.0018 ± 2<0.001
Status during echocardiography, mean ± SD
 Systolic blood pressure (mmHg)128 ± 15122 ± 140.14127 ± 220.82
 Diastolic blood pressure (mmHg)75 ± 972 ± 110.3473 ± 140.56
 Heart rate (min−1)76 ± 1179 ± 150.5778 ± 160.69
a

Control versus PMR.

b

Control versus SMR.

c

P-value <0.05, PMR versus SMR.

LV: left ventricle; MR: mitral regurgitation; PMR: primary mitral regurgitation; SD: standard deviation; SMR: secondary mitral regurgitation.

Anatomical mitral valve orifice area

Dynamic changes of AMVOA for MR groups and controls are compared in Table 2 and shown in Fig. 4A. Analysis showed the length of systole and diastole in all groups during 30% and 70% of the cardiac cycle, respectively. During mid-systole, the PMR group (0.9 ± 0.6 cm2) showed a larger AMVOA compared to the SMR group (0.4 ± 0.4 cm2). Control subjects showed no clinically significant systolic AMVOA. During early-systole, the AMVOA increased rapidly in all groups with a maximum AMVOA between the early-diastolic and mid-diastolic phases. The maximum AMVOA was found in the SMR group at 60% of the cardiac cycle. The control group showed a diastolic twin-peaked curve, which is abrogated in both MR groups.

Time-adjusted line plots of mitral annular dimensions and AMVOA throughout the cardiac cycle in the controls (black line) and patients with PMR (green line) and SMR (red line). In each panel, the systolic and diastolic phases were defined according to mitral valve opening and closing. (A) AMVOA. (B) AHCWR. (C) AP diameter. (D) LM diameter. (E) Annular circumference. (F) Annular area. (G) IT distance. (H) ASI. AHCWR: annular height to commissural width ratio; AMVOA: anatomical mitral valve orifice area; AP: anterior-posterior; ASI: annular sphericity index; IT: intertrigonal; LM: lateral-medial; PMR: primary mitral regurgitation; SMR: secondary mitral regurgitation.
Figure 4:

Time-adjusted line plots of mitral annular dimensions and AMVOA throughout the cardiac cycle in the controls (black line) and patients with PMR (green line) and SMR (red line). In each panel, the systolic and diastolic phases were defined according to mitral valve opening and closing. (A) AMVOA. (B) AHCWR. (C) AP diameter. (D) LM diameter. (E) Annular circumference. (F) Annular area. (G) IT distance. (H) ASI. AHCWR: annular height to commissural width ratio; AMVOA: anatomical mitral valve orifice area; AP: anterior-posterior; ASI: annular sphericity index; IT: intertrigonal; LM: lateral-medial; PMR: primary mitral regurgitation; SMR: secondary mitral regurgitation.

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Table 2:
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MV geometry throughout the cardiac cycle in controls, PMR and SMR

SystoleEarly-systole (10% of CC)
Mid-systole (20% of CC)
End-systole (30% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)0.2 ± 0.20.9 ± 0.5a0.5 ± 0.5c0.2 ± 0.10.9 ± 0.6a0.4 ± 0.4c0.3 ± 0.31.2 ± 1.0a0.5 ± 0.4c
Annular dimensions
 AP diameter (mm)26.9 ± 3.234.3 ± 4.4a33.4 ± 4.6b27.7 ± 3.635.5 ± 5.1a34.1 ± 4.6b28.1 ± 3.535.8 ± 5.1a35.1 ± 4.8b
 LM diameter (mm)35.5 ± 3.342.2 ± 6.0a40.1 ± 4.5b35.7 ± 3.542.3 ± 5.7a40.3 ± 4.8b36.0 ± 3.442.4 ± 5.7a40.7 ± 4.8b
 IT distance (mm)25.2 ± 3.327.0 ± 4.226.9 ± 3.525.0 ± 3.527.2 ± 4.027.2 ± 3.726.5 ± 3.827.5 ± 4.127.7 ± 4.0
 Annular circumference (mm)106.9 ± 9.7126.1 ± 16.6a122.2 ± 12.5b107.5 ± 10.3127.3 ± 16.0a123.3 ± 13.0b109.2 ± 9.8128.5 ± 16.8a124.6 ± 13.5b
 Annular area (cm2)8.2 ± 1.411.8 ± 3.1a11.2 ± 2.2b8.4 ± 1.612.1 ± 3.0a11.4 ± 2.3b8.5 ± 1.512.5 ± 3.3a11.7 ± 2.4b
Annular shape
 ASI0.76 ± 0.090.85 ± 0.09a0.86 ± 0.11b0.78 ± 0.090.88 ± 0.10a0.87 ± 0.12b0.79 ± 0.110.89 ± 0.08a0.89 ± 0.11b
 AHCWR0.25 ± 0.060.22 ± 0.070.21 ± 0.060.23 ± 0.060.20 ± 0.070.20 ± 0.060.21 ± 0.060.18 ± 0.060.20 ± 0.04
SystoleEarly-systole (10% of CC)
Mid-systole (20% of CC)
End-systole (30% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)0.2 ± 0.20.9 ± 0.5a0.5 ± 0.5c0.2 ± 0.10.9 ± 0.6a0.4 ± 0.4c0.3 ± 0.31.2 ± 1.0a0.5 ± 0.4c
Annular dimensions
 AP diameter (mm)26.9 ± 3.234.3 ± 4.4a33.4 ± 4.6b27.7 ± 3.635.5 ± 5.1a34.1 ± 4.6b28.1 ± 3.535.8 ± 5.1a35.1 ± 4.8b
 LM diameter (mm)35.5 ± 3.342.2 ± 6.0a40.1 ± 4.5b35.7 ± 3.542.3 ± 5.7a40.3 ± 4.8b36.0 ± 3.442.4 ± 5.7a40.7 ± 4.8b
 IT distance (mm)25.2 ± 3.327.0 ± 4.226.9 ± 3.525.0 ± 3.527.2 ± 4.027.2 ± 3.726.5 ± 3.827.5 ± 4.127.7 ± 4.0
 Annular circumference (mm)106.9 ± 9.7126.1 ± 16.6a122.2 ± 12.5b107.5 ± 10.3127.3 ± 16.0a123.3 ± 13.0b109.2 ± 9.8128.5 ± 16.8a124.6 ± 13.5b
 Annular area (cm2)8.2 ± 1.411.8 ± 3.1a11.2 ± 2.2b8.4 ± 1.612.1 ± 3.0a11.4 ± 2.3b8.5 ± 1.512.5 ± 3.3a11.7 ± 2.4b
Annular shape
 ASI0.76 ± 0.090.85 ± 0.09a0.86 ± 0.11b0.78 ± 0.090.88 ± 0.10a0.87 ± 0.12b0.79 ± 0.110.89 ± 0.08a0.89 ± 0.11b
 AHCWR0.25 ± 0.060.22 ± 0.070.21 ± 0.060.23 ± 0.060.20 ± 0.070.20 ± 0.060.21 ± 0.060.18 ± 0.060.20 ± 0.04
DiastoleEarly-diastole (40% of CC)
Mid-diastole (70% of CC)
End-diastole (100% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)2.4 ± 2.12.0 ± 1.72.1 ± 3.02.3 ± 0.93.8 ± 2.5a3.6 ± 1.4b0.2 ± 0.20.9 ± 0.6a0.7 ± 0.5b
Annular dimensions
 AP diameter (mm)27.9 ± 4.035.5 ± 5.3a35.5 ± 4.7b27.6 ± 3.134.1 ± 4.5a34.5 ± 4.7b25.8 ± 2.933.1 ± 4.4a33.1 ± 4.5b
 LM diameter (mm)36.5 ± 3.742.1 ± 5.8a40.6 ± 4.4b37.6 ± 3.441.6 ± 4.7a40.1 ± 4.735.0 ± 3.241.9 ± 5.4a39.8 ± 4.5b
 IT distance (mm)26.5 ± 3.827.5 ± 4.127.7 ± 4.026.5 ± 3.427.5 ± 4.227.2 ± 3.525.5 ± 3.127.7 ± 4.427.1 ± 3.3
 Annular circumference (mm)109.7 ± 9.7127.3 ± 17.0a124.1 ± 12.5b109.4 ± 9.2124.6 ± 14.8a122.9 ± 13.3b105.1 ± 8.8125.5 ± 15.6121.9 ± 12.7b
 Annular area (cm2)8.5 ± 1.612.3 ± 3.3a11.6 ± 2.3b8.5 ± 1.411.7 ± 2.8a11.3 ± 2.3b7.8 ± 1.211.7 ± 2.9a11.1 ± 2.2b
Annular shape
 ASI0.77 ± 0.110.90 ± 0.09a0.91 ± 0.12b0.76 ± 0.110.85 ± 0.07a0.89 ± 0.11b0.74 ± 0.090.83 ± 0.08a0.85 ± 0.11b
 AHCWR0.17 ± 0.060.16 ± 0.050.17 ± 0.050.15 ± 0.050.15 ± 0.040.19 ± 0.050.25 ± 0.070.22 ± 0.070.21 ± 0.06
DiastoleEarly-diastole (40% of CC)
Mid-diastole (70% of CC)
End-diastole (100% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)2.4 ± 2.12.0 ± 1.72.1 ± 3.02.3 ± 0.93.8 ± 2.5a3.6 ± 1.4b0.2 ± 0.20.9 ± 0.6a0.7 ± 0.5b
Annular dimensions
 AP diameter (mm)27.9 ± 4.035.5 ± 5.3a35.5 ± 4.7b27.6 ± 3.134.1 ± 4.5a34.5 ± 4.7b25.8 ± 2.933.1 ± 4.4a33.1 ± 4.5b
 LM diameter (mm)36.5 ± 3.742.1 ± 5.8a40.6 ± 4.4b37.6 ± 3.441.6 ± 4.7a40.1 ± 4.735.0 ± 3.241.9 ± 5.4a39.8 ± 4.5b
 IT distance (mm)26.5 ± 3.827.5 ± 4.127.7 ± 4.026.5 ± 3.427.5 ± 4.227.2 ± 3.525.5 ± 3.127.7 ± 4.427.1 ± 3.3
 Annular circumference (mm)109.7 ± 9.7127.3 ± 17.0a124.1 ± 12.5b109.4 ± 9.2124.6 ± 14.8a122.9 ± 13.3b105.1 ± 8.8125.5 ± 15.6121.9 ± 12.7b
 Annular area (cm2)8.5 ± 1.612.3 ± 3.3a11.6 ± 2.3b8.5 ± 1.411.7 ± 2.8a11.3 ± 2.3b7.8 ± 1.211.7 ± 2.9a11.1 ± 2.2b
Annular shape
 ASI0.77 ± 0.110.90 ± 0.09a0.91 ± 0.12b0.76 ± 0.110.85 ± 0.07a0.89 ± 0.11b0.74 ± 0.090.83 ± 0.08a0.85 ± 0.11b
 AHCWR0.17 ± 0.060.16 ± 0.050.17 ± 0.050.15 ± 0.050.15 ± 0.040.19 ± 0.050.25 ± 0.070.22 ± 0.070.21 ± 0.06
a

P-value  <0.05, control versus PMR.

b

P-value <0.05, control versus SMR.

c

P-value <0.05, PMR versus SMR.

AHCWR: annular height to commissural width ratio; AMVOA: anatomical mitral valve orifice area; AP: anteroposterior; ASI: annular sphericity index; CC: cardiac cycle; IT: intertrigonal; LM: anterolateral-posteromedial; MV: mitral valve; PMR: primary mitral regurgitation; SMR: secondary mitral regurgitation.

Table 2:
Open in new tab

MV geometry throughout the cardiac cycle in controls, PMR and SMR

SystoleEarly-systole (10% of CC)
Mid-systole (20% of CC)
End-systole (30% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)0.2 ± 0.20.9 ± 0.5a0.5 ± 0.5c0.2 ± 0.10.9 ± 0.6a0.4 ± 0.4c0.3 ± 0.31.2 ± 1.0a0.5 ± 0.4c
Annular dimensions
 AP diameter (mm)26.9 ± 3.234.3 ± 4.4a33.4 ± 4.6b27.7 ± 3.635.5 ± 5.1a34.1 ± 4.6b28.1 ± 3.535.8 ± 5.1a35.1 ± 4.8b
 LM diameter (mm)35.5 ± 3.342.2 ± 6.0a40.1 ± 4.5b35.7 ± 3.542.3 ± 5.7a40.3 ± 4.8b36.0 ± 3.442.4 ± 5.7a40.7 ± 4.8b
 IT distance (mm)25.2 ± 3.327.0 ± 4.226.9 ± 3.525.0 ± 3.527.2 ± 4.027.2 ± 3.726.5 ± 3.827.5 ± 4.127.7 ± 4.0
 Annular circumference (mm)106.9 ± 9.7126.1 ± 16.6a122.2 ± 12.5b107.5 ± 10.3127.3 ± 16.0a123.3 ± 13.0b109.2 ± 9.8128.5 ± 16.8a124.6 ± 13.5b
 Annular area (cm2)8.2 ± 1.411.8 ± 3.1a11.2 ± 2.2b8.4 ± 1.612.1 ± 3.0a11.4 ± 2.3b8.5 ± 1.512.5 ± 3.3a11.7 ± 2.4b
Annular shape
 ASI0.76 ± 0.090.85 ± 0.09a0.86 ± 0.11b0.78 ± 0.090.88 ± 0.10a0.87 ± 0.12b0.79 ± 0.110.89 ± 0.08a0.89 ± 0.11b
 AHCWR0.25 ± 0.060.22 ± 0.070.21 ± 0.060.23 ± 0.060.20 ± 0.070.20 ± 0.060.21 ± 0.060.18 ± 0.060.20 ± 0.04
SystoleEarly-systole (10% of CC)
Mid-systole (20% of CC)
End-systole (30% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)0.2 ± 0.20.9 ± 0.5a0.5 ± 0.5c0.2 ± 0.10.9 ± 0.6a0.4 ± 0.4c0.3 ± 0.31.2 ± 1.0a0.5 ± 0.4c
Annular dimensions
 AP diameter (mm)26.9 ± 3.234.3 ± 4.4a33.4 ± 4.6b27.7 ± 3.635.5 ± 5.1a34.1 ± 4.6b28.1 ± 3.535.8 ± 5.1a35.1 ± 4.8b
 LM diameter (mm)35.5 ± 3.342.2 ± 6.0a40.1 ± 4.5b35.7 ± 3.542.3 ± 5.7a40.3 ± 4.8b36.0 ± 3.442.4 ± 5.7a40.7 ± 4.8b
 IT distance (mm)25.2 ± 3.327.0 ± 4.226.9 ± 3.525.0 ± 3.527.2 ± 4.027.2 ± 3.726.5 ± 3.827.5 ± 4.127.7 ± 4.0
 Annular circumference (mm)106.9 ± 9.7126.1 ± 16.6a122.2 ± 12.5b107.5 ± 10.3127.3 ± 16.0a123.3 ± 13.0b109.2 ± 9.8128.5 ± 16.8a124.6 ± 13.5b
 Annular area (cm2)8.2 ± 1.411.8 ± 3.1a11.2 ± 2.2b8.4 ± 1.612.1 ± 3.0a11.4 ± 2.3b8.5 ± 1.512.5 ± 3.3a11.7 ± 2.4b
Annular shape
 ASI0.76 ± 0.090.85 ± 0.09a0.86 ± 0.11b0.78 ± 0.090.88 ± 0.10a0.87 ± 0.12b0.79 ± 0.110.89 ± 0.08a0.89 ± 0.11b
 AHCWR0.25 ± 0.060.22 ± 0.070.21 ± 0.060.23 ± 0.060.20 ± 0.070.20 ± 0.060.21 ± 0.060.18 ± 0.060.20 ± 0.04
DiastoleEarly-diastole (40% of CC)
Mid-diastole (70% of CC)
End-diastole (100% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)2.4 ± 2.12.0 ± 1.72.1 ± 3.02.3 ± 0.93.8 ± 2.5a3.6 ± 1.4b0.2 ± 0.20.9 ± 0.6a0.7 ± 0.5b
Annular dimensions
 AP diameter (mm)27.9 ± 4.035.5 ± 5.3a35.5 ± 4.7b27.6 ± 3.134.1 ± 4.5a34.5 ± 4.7b25.8 ± 2.933.1 ± 4.4a33.1 ± 4.5b
 LM diameter (mm)36.5 ± 3.742.1 ± 5.8a40.6 ± 4.4b37.6 ± 3.441.6 ± 4.7a40.1 ± 4.735.0 ± 3.241.9 ± 5.4a39.8 ± 4.5b
 IT distance (mm)26.5 ± 3.827.5 ± 4.127.7 ± 4.026.5 ± 3.427.5 ± 4.227.2 ± 3.525.5 ± 3.127.7 ± 4.427.1 ± 3.3
 Annular circumference (mm)109.7 ± 9.7127.3 ± 17.0a124.1 ± 12.5b109.4 ± 9.2124.6 ± 14.8a122.9 ± 13.3b105.1 ± 8.8125.5 ± 15.6121.9 ± 12.7b
 Annular area (cm2)8.5 ± 1.612.3 ± 3.3a11.6 ± 2.3b8.5 ± 1.411.7 ± 2.8a11.3 ± 2.3b7.8 ± 1.211.7 ± 2.9a11.1 ± 2.2b
Annular shape
 ASI0.77 ± 0.110.90 ± 0.09a0.91 ± 0.12b0.76 ± 0.110.85 ± 0.07a0.89 ± 0.11b0.74 ± 0.090.83 ± 0.08a0.85 ± 0.11b
 AHCWR0.17 ± 0.060.16 ± 0.050.17 ± 0.050.15 ± 0.050.15 ± 0.040.19 ± 0.050.25 ± 0.070.22 ± 0.070.21 ± 0.06
DiastoleEarly-diastole (40% of CC)
Mid-diastole (70% of CC)
End-diastole (100% of CC)
VariablesControlPMRSMRControlPMRSMRControlPMRSMR
AMVOA (cm2)2.4 ± 2.12.0 ± 1.72.1 ± 3.02.3 ± 0.93.8 ± 2.5a3.6 ± 1.4b0.2 ± 0.20.9 ± 0.6a0.7 ± 0.5b
Annular dimensions
 AP diameter (mm)27.9 ± 4.035.5 ± 5.3a35.5 ± 4.7b27.6 ± 3.134.1 ± 4.5a34.5 ± 4.7b25.8 ± 2.933.1 ± 4.4a33.1 ± 4.5b
 LM diameter (mm)36.5 ± 3.742.1 ± 5.8a40.6 ± 4.4b37.6 ± 3.441.6 ± 4.7a40.1 ± 4.735.0 ± 3.241.9 ± 5.4a39.8 ± 4.5b
 IT distance (mm)26.5 ± 3.827.5 ± 4.127.7 ± 4.026.5 ± 3.427.5 ± 4.227.2 ± 3.525.5 ± 3.127.7 ± 4.427.1 ± 3.3
 Annular circumference (mm)109.7 ± 9.7127.3 ± 17.0a124.1 ± 12.5b109.4 ± 9.2124.6 ± 14.8a122.9 ± 13.3b105.1 ± 8.8125.5 ± 15.6121.9 ± 12.7b
 Annular area (cm2)8.5 ± 1.612.3 ± 3.3a11.6 ± 2.3b8.5 ± 1.411.7 ± 2.8a11.3 ± 2.3b7.8 ± 1.211.7 ± 2.9a11.1 ± 2.2b
Annular shape
 ASI0.77 ± 0.110.90 ± 0.09a0.91 ± 0.12b0.76 ± 0.110.85 ± 0.07a0.89 ± 0.11b0.74 ± 0.090.83 ± 0.08a0.85 ± 0.11b
 AHCWR0.17 ± 0.060.16 ± 0.050.17 ± 0.050.15 ± 0.050.15 ± 0.040.19 ± 0.050.25 ± 0.070.22 ± 0.070.21 ± 0.06
a

P-value  <0.05, control versus PMR.

b

P-value <0.05, control versus SMR.

c

P-value <0.05, PMR versus SMR.

AHCWR: annular height to commissural width ratio; AMVOA: anatomical mitral valve orifice area; AP: anteroposterior; ASI: annular sphericity index; CC: cardiac cycle; IT: intertrigonal; LM: anterolateral-posteromedial; MV: mitral valve; PMR: primary mitral regurgitation; SMR: secondary mitral regurgitation.

Annular dimensions

Time-adjusted mitral annular dimensions among the MR groups and the controls are compared in Table 2 and shown in Fig. 4C–G. Annular dimensions were larger in the MR groups compared to the control group. In all groups, a systolic increase of all annular parameters with a maximum during the early-diastolic phase was found. Compared to MR groups, the control group showed a more active late-diastolic contraction, which decreased the annular dimensions during end-diastole.

The largest annular circumference and MV orifice area were found in the PMR group. The difference between the PMR and the SMR groups can be explained by a smaller LM diameter in the SMR group compared to the PMR group.

The smallest absolute differences between all groups were found in the IT distance. The maximum difference between the MR groups and the control group was 2.2 mm during mid-systole.

Annular shape

The dynamic changes in the annular shape represent the changes of AHCWR and ASI in Table 2 and in Fig. 4. Based on the pathophysiological mechanism of MR, annular enlargement leads to a decrease of AHCWR in the MR groups during systole and late diastole compared to the control subjects. In all groups, AHCWR was decreased during systole, followed by an early-diastolic plateau phase and an end-diastolic increase.

The ASIs in the MR groups were larger compared to those in the control group. This result demonstrates a rounder annular shape in patients with MR compared to a more oval shape of control subjects without clinically significant MR.

Relationships between annular dimensions in the control group

The mid-systolic relationship between the AP and LM diameters, the IT distance and the ASI for the control group is shown in Fig. 5. Scatterplots with regression lines for the annular diameters with the IT distance demonstrated a positive association with the increase of AP and LM diameters (Fig. 5A and B). Furthermore, the AP and LM diameters show a linear association throughout the range of measurements (Fig. 5C).

Scatter plots with regression lines demonstrate the linear relationship between different annular dimensions (A–C) in the control group during mid-systole (20% of the cardiac cycle). The ASI is not influenced by the increase of the IT distance (D). AP: anteroposterior; ASI: annular sphericity index; IT: intertrigonal; LM: lateral-medial.
Figure 5:

Scatter plots with regression lines demonstrate the linear relationship between different annular dimensions (A–C) in the control group during mid-systole (20% of the cardiac cycle). The ASI is not influenced by the increase of the IT distance (D). AP: anteroposterior; ASI: annular sphericity index; IT: intertrigonal; LM: lateral-medial.

Open in new tabDownload slide

The scatterplot for ASI and IT distance demonstrates (Fig. 5D) that the ASI is not affected by an increase of IT distance, and the regression line correlates with the mean ASI of 0.78 at mid-systole in the control group (Table 2).

The geometrical relationship between AP diameter, LM diameter and IT distance at 20% of the cardiac cycle can be summarized as follows: AP diameter = 1.1 × IT distance and LM diameter = 1.4 × IT distance.

DISCUSSION

We analysed for the first time the annular dimensions, the annular shape and the AMVOA simultaneously throughout the cardiac cycle in patients with PMR and SMR and compared these findings with those of subjects without any clinically significant heart valve disease. We found anatomical associations between IT distance and AP and LM diameters in the control group, which could have a significant clinical impact for the treatment of annular dilation by surgical or interventional annuloplasty in patients with SMR and PMR.

Geometry and dynamic in the normal mitral valve

Among the controls, we noted dynamic changes in the MV annulus with an annular enlargement during systole, followed by an early- to mid-diastolic plateau phase (Fig. 4C–F). The cardiac cycle was finished by an end-diastolic annular contraction. Compared with CT-based quantification of mid-diastolic AP diameter and LM diameter, the data in the present study with 27.6 and 36.5 mm correspond exactly with previous CT-based measurements of 27.5 and 37.6 mm, respectively [7] and demonstrates the comparability of 3D-TOE-based 4D MV analysis with CT [6].

The end-diastolic reduction of annular parameters can be defined as end-diastolic annular contraction, which converges towards MV competency during systole and prevents regurgitation. This finding is contrary to the previous assumption of an early-systolic area contraction and deepening of the saddle shape, thereby contributing to MV competency [1, 19]. The differently used temporal resolutions in the TOE data sets and 4D MV analysis in the studies may explain this main difference. Grewal et al. investigated the MV annulus at 6 predefined time points of the cardiac cycle, whereas we used a higher temporal resolution, which allows an improved temporal analysis of dynamic changes, particularly during phases of fast dynamic changes such as MV opening and closing.

Furthermore, previous investigators have reported that the annular contraction leads to a reduction of the AP diameter but not to a reduction of LM diameter. We observed a reduction of both parameters. This finding could be explained by the fact that the lateral, posterior and medial parts of the mitral annulus are mainly muscular, and a contraction can also affect the LM diameter.

It is well known that the annular contraction leads to an increase of AHCWR, which contributes to the mitral coaptation because the central parts of the leaflets are positioned more apically, resulting in less chordal traction and may participate in homeostasis of the ventriculomitral complex [1, 20, 21]. This phenomenon could also be demonstrated in this study (Fig. 4B).

The ASI shows minimal changes throughout the cardiac cycle with a systolic increase and diastolic decrease (Fig. 4H). The systolic ventricular contraction with an increase of the left ventricle pressure could lead to an annular prolongation, which contributes to the MV opening. During end-systole, the mitral annulus changes from an oval (early-systolic ASI 0.76) to a rounder (end-systolic ASI 0.79) shape.

In previous studies, the influence of atrial contraction on annular shape was not detected or theoretically discussed [1, 11, 22]. In the present study, the course of the AMVOA over the entire cardiac cycle (Fig. 4A) in control subjects shows a twin-peaked curve, which can be explained by early mitral inflow (first peak, E wave) and atrial contraction (second peak, A wave). Compared with the annular parameters, we found late-diastolic (70–90% of the cardiac cycle) changes of annular dimensions, which correspond to the atrial contraction observed in AMVOA. We interpreted these synchronic changes as an influence of atrial contraction on the annular dimensions (Fig. 4C–F) and annular shape (Fig. 4B and H). The atrial contraction leads to an abrupt late-diastolic reduction of annular dimensions and could theoretically contribute to systolic MV competency. This effect is missing in both MR groups due to the prevalence of atrial fibrillation, which confirms our interpretation.

Geometry and dynamic in mitral regurgitation

Mitral regurgitation is associated with annular dilation compared to control subjects. Patients with PMR and SMR show the same dilatation in the AP direction, but the LM diameter was larger in the PMR group (Fig. 4C–F). This finding could be explained by the different underlying patho-mechanisms of MR. PMR can be associated with a tissue deficiency, which leads to an annular dilation of all the mainly muscular parts of the annulus and thus affects the mitral annulus in the AP and LM directions [1, 23]. SMR is mostly caused by cardiomyopathy with dislocation of the subvalvular apparatus or rarely by atrial dilatation with isolated annular dilatation and more strongly affects the mitral annulus in the AP direction [23]. The underlying patho-mechanism with annular dilatation leads to a more planar mitral annulus, which can be observed in the reduction of AHCWR. The summation of a pathologically geometric dislocation leads to a loss of leaflet coaptation with progression of regurgitation.

Compared with the annular dynamic in the control group, dynamic changes of annular geometry in patients with MR were found only in the AP direction with enlargement during systole and diastolic reduction.

Independently from these findings, MR leads to a rounder shape of the mitral annulus compared to the control groups (Fig. 4H).

In all MR groups, greater diastolic AMVOA could be observed compared to the controls. Furthermore, in the PMR and SMR groups, the twin-peaked course was abrogated compared to the control subjects. This finding could be explained by the higher prevalence of atrial fibrillation (PMR group: 59%; SMR group: 68%) compared to the control group (6%) with loss of atrial contraction.

Annular dimensions with implications for annuloplasty ring sizing

The IT distance in both MR groups was the least affected annular parameter in this study compared to the control group and the other annular parameters. This finding can be explained by the fibrous continuity between the aortic valve with the anterior leaflet and the lateral and medial fibrous trigones [2]. This region of the mitral annulus is thus fibrous and less prone to dilatation than the posterior part of mitral annulus, which is mainly muscular and more prone to dilatation or calcification [2].

Based on our and previous findings, we hypothesized a linear association between the IT distance and the AP and LM diameters in the control subjects. Our results support this hypothesis (Fig. 5), and the anatomical association between these structures can be summarized as follows: (i) AP diameter = 1.1 × IT distance; (ii) LM diameter = 1.4 × IT distance; (iii) linear association over the entire measurement range; and (iv) same annular shape, based on ASI, over the entire measurement range.

Based on the anatomical associations between the IT distance and the AP and LM diameters in the control group, it can be hypothesized that, with the quantification of the IT distance in patients with MR, a determination of the physiological ‘truth’ AP and LM diameter could be possible. Based on this assumption, a preoperative determination of the annuloplasty ring size (‘truth’ sizing concept) can lead to an improvement in surgical planning and annuloplasty ring selection and should be investigated in further clinical studies.

Clinical implications

Prior studies have investigated the geometric and dynamic changes of the mitral annulus only. With the use of novel 4D MV analysis software, we investigated the dynamic changes of the MV annulus, shape and AMVOA simultaneously in patients with PMR and SMR compared to control subjects. The present study conveyed several important and unique results that clearly differ from results from previous studies: (i) our findings demonstrated for the first time the complex dynamic interactions between the mitral annulus and the leaflets that improve the physiological understanding of the normal MV and, more importantly, elucidate the patho-mechanisms of the MR. (ii) We could demonstrate a late-diastolic annular contraction in control subjects, which improves the systolic MV competency. Further we found an influence of atrial contraction on annular geometry and shape in controls, which was abrogated in patients with MR, and a higher prevalence of atrial fibrillation. (iii) Patients with MR have a rounder shaped and planar annular dilatation with less dilatation in the LM direction in SMR compared to PMR. (iv) Pending further validation, the IT distance-based ‘truth’ sizing concept could potentially be used as a predictor for annuloplasty ring size. (v) Furthermore, 4D MV analysis allows improved understanding of dynamic MV geometry in patients with PMR or SMR and can be rapidly made in clinical settings. For surgical or interventional planning of MV repair, end-diastolic and end-systolic annular dimensions should be used for determining annuloplasty ring size.

The improved understandings of MV geometry in patients with PMR or SMR, assessed by 4D MV analysis, will improve MV repair strategies and functional clinical outcome after MV repair.

Limitations

The limited number of patients in this study may slightly reduce its clinical applicability. However, given the novelty of the 4D MV advanced analysis, we believe that the present sample size is very reasonable to reach meaningful conclusions.

In addition, we did not investigate the influence of arrhythmia on the time-adjusted measurements.

Finally, in this study, the maximal AMVOA is a time-dependent measure reliant on the length of the cardiac cycle. The time-dependent maximal AMVOA underestimates the true maximal MV orifice area during the MV opening due to the divergent times of MV opening between patients.

CONCLUSION

The novel 4D MV analysis shows that the normal MV is a highly dynamic structure with complex changes throughout the cardiac cycle. The interaction of the different anatomical structures of the MV complex leads to optimal MV function with systolic mitral inflow and preservation of diastolic regurgitation.

MR is associated with a less dynamic, planar and dilated annulus with small variations between PMR and SMR. The analysis underlines the important role of ring annuloplasty in the treatment of MR. The less affected IT distance by MR may be used to predict the annuloplasty ring size and represents an important target for annuloplasty device selection.

Conflict of interest: Thilo Noack has received research grants and lecture fees from Siemens Healthineers.

Footnotes

†

Presented at the 32nd Annual Meeting of the European Association for Cardio-Thoracic Surgery, Milan, Italy, 18–20 October 2018.

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© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
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