Adaptive enlargement of the mitral leaflet has been implied to participate in the pathogenesis of functional mitral regurgitation (FMR). The aim of the present study was to observe the elongation pattern of anterior mitral leaflets (AML) and posterior mitral leaflets (PML) in idiopathic dilated cardiomyopathy (DC) and to explore its relation with FMR. Forty normal controls (control group) and 97 patients with idiopathic DC (group DC 0-1+: 36 patients with no or only mild FMR; group DC >1+: 61 patients with more-than-mild FMR) were consecutively recruited. The lengths of AML and PML were measured at the parasternal long-axis view (AML-lax, PML-lax) and apical 4-chamber view (AML-4, PML-4) using 2-dimensional echocardiography, as well as tenting height (TH) and mitral annular dimension (MAD). Both AML (AML-lax: 2.4 ± 0.3 vs 3.0 ± 0.3 vs 3.1 ± 0.3 cm; AML-4: 1.9 ± 0.2 vs 2.5 ± 0.3 vs 2.6 ± 0.4 cm) and PML (PML-lax: 1.3 ± 0.3 vs 2.1 ± 0.5 vs 2.5 ± 0.4 cm; PML-4: 1.1 ± 0.2 vs 1.6 ± 0.3 vs 1.8 ± 0.4 cm) were elongated in the DC groups compared to controls (all p <0.001). There was a further elongation of PML in group DC >1+ than in group DC 0-1+ (p <0.05), but the AML length was not different (p >0.05). The ratio of (AML-lax + PML-lax)/(TH-lax + MAD-lax) (1.03 ± 0.10 vs 1.08 ± 0.09, p <0.05) or AML-lax/(TH-lax + MAD-lax) (0.57 ± 0.06 vs 0.64 ± 0.08, p <0.001) in group DC >1+ was significantly smaller compared to group DC 0-1+, whereas the ratio of PML-lax/(TH-lax + MAD-lax) was similar between the 2 groups (0.46 ± 0.06 vs 0.44 ± 0.07, p = 0.138). In conclusion, both the AML and PML were elongated in idiopathic DC, but the extent and pattern were not identical between the 2 leaflets. Inadequate AML elongation proportional to mitral apparatus remodeling more likely contributes to the pathogenesis of FMR.
Functional mitral regurgitation (FMR) is a common complication of left ventricular (LV) dilation and systolic dysfunction. The mitral leaflets had been viewed as passive participants in the disease process because no morphologic change has been observed on echocardiographic or gross pathologic examination. However, several recent imaging studies implied that adaptive change of the mitral leaflet occurred in the disease process of congestive heart failure, and insufficient adaptation in relation to mitral apparatus remodeling might be another factor contributing to the pathogenesis of FMR. Nevertheless, there were only a few in vivo studies which investigated the total leaflet area rather than the differential changes between the 2 leaflets. Therefore, the present study aimed to observe the differential elongation patterns between the anterior mitral leaflet (AML) and posterior mitral leaflet (PML) by 2-dimensional (2D) echocardiography in patients with nonischemic dilated cardiomyopathy (DC) and to explore the sufficiency of leaflet elongation to apparatus regional remodeling and its relation with the degree of FMR.
Methods
Subjects with a normal heart according to echocardiography were enrolled as controls (n = 40). From May 2013 to June 2014, 113 patients diagnosed as nonischemic DC with symptomatic heart failure and LV systolic dysfunction (LV ejection fraction [EF] <50% measured by biplane Simpson method of echocardiography) were consecutively recruited. Those with ischemic heart disease, evidence of other cardiac diseases (such as valvular, pericardial, congenital, or infiltrative heart disease), organic mitral valve disease, and mitral valve surgery were excluded. Moreover, 16 patients with identifiable underlying causes of LV dysfunction were also excluded, whereas the other 97 patients were labeled as idiopathic DC for final analysis. Patients were divided into 2 groups, as DC 0-1+ (n = 36, i.e., patients with no or only mild FMR) and DC >1+ (n = 61, i.e., patients with more-than-mild FMR). The study protocol was approved by the ethics committee of the institution, and written informed consents were obtained from all the patients.
Standard transthoracic echocardiography was performed in all patients using Philips iE33 scanner and a 5-MHz transducer. At the parasternal long-axis view, the scan plane paralleled with the LV long axis to show the aortic root, right coronary and noncoronary cusps of the aortic valve. Of note, posterior papillary muscles should be avoided, and the largest short-axis dimension of LV should be displayed by slightly adjusting the transducer. At the apical 4-chamber view, the full length of LV should be presented without foreshortening. More importantly, both anterior and posterior leaflet tips must be differentiated from chords throughout the whole cardiac cycle.
Offline analyses on mitral leaflet length and other echocardiographic variables including mitral regurgitation (MR) severity were performed by 2 independent observers who were blinded to the results of each other. MR jet area and left atrial (LA) area were measured at the same frame in apical 4-chamber view. FMR severity was qualified by the MR jet area ratio [(MR jet area/LA area) × 100%], where more-than-mild MR was defined as the ratio ≥20%, and no or only mild MR was defined as the ratio <20%. In the latter group, undetectable MR or untraceable trivial MR was treated as no MR with the ratio of 0. The lengths of AML or PML were measured from the leaflet tip to its insertion point during mid-diastole at the parasternal long-axis view (AML-lax, PML-lax) and apical-4 chamber view (AML-4, PML-4), respectively. At mid-systole, mitral tenting height (TH) and mitral annular dimension (MAD) were measured at the parasternal long-axis view as (TH-lax) and (MAD-lax). The ratios of (AML-lax + PML-lax)/(TH-lax + MAD-lax), AML-lax/(TH-lax + MAD-lax), and PML-lax/(TH-lax + MAD-lax) were calculated to reflect the relation between structural change of mitral leaflet and regional remodeling of mitral apparatus.
The statistical analyses were carried out using SPSS (version 13.0). Continuous variables were expressed as mean ± SD, whereas categorical data as frequencies and percentages. One-way analysis of variance or Pearson chi-square test was used when appropriate to compare the 3 groups. A p value <0.05 (2-sided) was considered statistically significant. Reproducibility was assessed using intraclass correlation coefficients. Interobserver and intraobserver variabilities for measurements of AML, PML, TH, and MAD were obtained in 20 randomly selected images by 2 independent blinded observers who performed the offline analysis twice on 2 different days. Good correlations were demonstrated for both intraobserver and interobserver reliabilities, with intraclass correlation coefficients ranging from 0.751 to 0.913.
Results
Baseline characteristics are summarized in Table 1 . In the group DC 0-1+, there were 17 patients (47%) with no or trivial FMR and 19 (53%) patients with mild FMR. In the group DC >1+, there were 45 patients (74%) with moderate FMR (20% ≤ MR jet area ratio < 40%) and 16 (26%) with severe FMR (MR jet area ratio ≥40%).
| Variables | Functional MR | |||
|---|---|---|---|---|
| Control (n = 40) | DC 0-1+ (n = 36) | DC >1+ (n = 61) | DC 0-1+ vs. DC >1+ | |
| Age (years) | 52±11 | 51±14 | 54±13 | 0.216 |
| Male | 48% | 89% ∗ | 59% | 0.001 |
| Body surface area (m 2 ) | 1.6±0.1 | 1.7±0.1 | 1.7±0.2 | 0.281 |
| Systolic blood pressure (mmHg) | 129±13 | 116±15 ∗ | 112±16 ∗ | 0.303 |
| Diastolic blood pressure (mmHg) | 75±8 | 69±9 & | 66±9 ∗ | 0.186 |
| Heart rate (beat per minute) | 69±9 | 76±13 # | 80±14 ∗ | 0.116 |
| MR jet ratio (%) | – | 10.7±6.4 | 34.6±11.4 | <0.001 |
| LV end-diastolic volume (ml) | 79±15 | 228±84 ∗ | 278±83 ∗ | 0.001 |
| LV end-systolic volume (ml) | 29±7 | 164±63 ∗ | 205±62 ∗ | <0.001 |
| LV ejection fraction (%) | 63±4 | 28±8 ∗ | 25±8 ∗ | 0.083 |
| NYHA class | 0.271 | |||
| III | – | 100% | 91% | |
| IV | – | 0 | 9% | |
| Medications | ||||
| ACEI or ARB | – | 83% | 86% | 0.761 |
| β-receptor blocker | – | 80% | 77% | 0.792 |
| Diuretic | – | 83% | 75% | 0427 |
| Digoxin | – | 30% | 41% | 0.356 |
| Nitroglycerin | – | 0 | 7% | 0.293 |
In the control group, there were no differences in the AML and PML parameters between men and women, between different age groups (age ≥50 vs <50 years), and between different body figures (BSA ≥1.64 vs <1.64 m 2 ). Table 2 demonstrates that both AML and PML were elongated in the 2 DC groups compared to the control group. There was a further elongation of PML in group DC >1 + than in group DC 0-1+, but the length of AML was not different between the 2 groups. Compared to the control group, the PML-lax was elongated by 62% and 92% and the PML-4 by 45% and 64% in groups DC 0-1+ and DC >1+, respectively. On the contrary, the elongation was achieved at a lesser degree, that is 25% and 29% for the AML-lax, 32% and 37% for the AML-4, respectively. Therefore, the difference between AML and PML was shrunk in the 2 DC groups (control vs DC 0-1+ vs DC >1+: 1.9 ± 0.5 vs 1.5 ± 0.4 vs 1.2 ± 0.2 times at the parasternal long-axis view, p <0.001; 1.8 ± 0.6 vs 1.6 ± 0.3 vs 1.5 ± 0.4 times at the apical 4-chamber view, p = 0.005).
| Variables | Functional MR | |||
|---|---|---|---|---|
| Control (n = 40) | DC 0-1+ (n = 36) | DC >1+ (n = 61) | DC 0-1+ vs. DC >1+ | |
| AML-lax (cm) | 2.4±0.3 | 3.0±0.3 ∗ | 3.1±0.3 ∗ | 0.093 |
| PML-lax (cm) | 1.3±0.3 | 2.1±0.5 ∗ | 2.5±0.4 ∗ | <0.001 |
| AML-4 (cm) | 1.9±0.2 | 2.5±0.3 ∗ | 2.6±0.4 ∗ | 0.313 |
| PML-4 (cm) | 1.1±0.2 | 1.6±0.3 ∗ | 1.8±0.4 ∗ | 0.032 |
Not surprisingly, the 2 groups with idiopathic DC had obviously mitral apparatus remodeling, as reflected by the increase in its size and the change in its shape (all p <0.01; Table 3 ). Despite elongated mitral leaflets in the 2 DC groups, the (AML-lax + PML-lax)/(TH-lax + MAD-lax) was smaller in group DC > 1+ (both p <0.05), which appeared comparable between groups control and DC 0-1+ (p = 0.676). The ratio of AML-lax/(TH-lax + MAD-lax) showed a similar trend with the smallest value seen in group DC >1+ (both p <0.001). However, the ratio of PML-lax/(TH-lax + MAD-lax) was increased in the 2 DC groups ( Table 3 , Figures 1 and 2 ).
