Revealing mitral valve cleft using real-time 3-dimensional echocardiography in children with mitral regurgitation

doi:10.21203/rs.3.rs-2487575/v1

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Revealing mitral valve cleft using real-time 3-dimensional echocardiography in children with mitral regurgitation

https://doi.org/10.21203/rs.3.rs-2487575/v1

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Journal Publication

published 05 Apr, 2023

Read the published version in Pediatric Cardiology →

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Background:Mitral valve cleft (MVC) is the most common cause of congenital mitral regurgitation (MR). MVC may be located on the anterior or posterior leaflets. We evaluated children with moderate-to-severe MR using 3D transthoracic echocardiography (3DTTE) to diagnose MVC and determine the location, shape and size of MVC.

Methods:Twenty-one patients under 18 years of age with moderate to severe MR without symptoms who were suspected of having MVC were in included in the study. The patients’ history and clinical data were obtained from the medical records. 2D and 3D imaging were performed with a high-quality machine (EPIQ CVx). A vena contracta (VC) of colour Doppler regurgitated jet 3-7 and ≥7 mm defined moderate-to-severe regurgitation.

Results: An isolated anterior leaflet cleft (ALC) was detected in four patients, an isolated posterior leaflet cleft (PLC) in 12 patients, and both an ALC and PLC in five patients. VC was higher in patients with ALCs than PLCs (8.85 mm vs. 6.64 mm). Global LV longitudinal strain was lower in the ALC group than in the PLC and both-posterior-and anterior MVC groups (–24.7, –24.3, and –24%, respectively). Global circumferential strain was lower in the ALC group (–28.9%) and similarly reduced in the both-posterior-and-anterior MVC group (–28.6%).

Conclusion:3DTTE for visualisation of the MV can be successfully implemented in children and should be proposed during follow-up. AMVC and bi-leaflet MVC results in severe regurgitation and can cause early systolic dysfunction.

Mitral valve cleft

3D echocardiography

mitral regurgitation.

An isolated mitral valve cleft (MVC) is characterised as an anatomic defect that is not associated with a septal defect or ostium primum atrial septal defect. MVC is the most common cause of congenital mitral regurgitation (MR) [1], which can have varying severity. MVCs may be located on the anterior or posterior leaflets, although isolated anterior mitral leaflet clefts are uncommon [2]. Previous reports have suggested that children with symptoms and/or moderate MR are indicated for surgical management, even if they are asymptomatic [3].

The diagnosis of MVC in children using transthoracic echocardiography is particularly challenging. Three-dimensional echocardiography (3DE) allows anatomic visualisation of the MV. Thus, identification of the mechanisms of MR in children in whom the diagnosis is otherwise unclear on the basis of 2D echocardiography (2DE) can be achieved with 3DE [4]. In this study, we evaluated children with moderate-to-severe MR using 3DE to diagnose MVC and to determine the location, shape and size of MVC.

A total of 79 consecutive patients under age of 18 years with moderate-to-severe MR without symptoms seen during 2019-22 were included in our single-centre observational study. MR patients were included with or without MVP, defined as dislocation of at least one segment of the MV by 2 mm relative to the hinge points of the leaflet tip into the left atrium (LA). Of the initial 79 patients, only those who had undergone echocardiography (ECHO) and were suspected of having MVC were included, while those with atrioventricular septal defect features on the echocardiogram or abnormal atrioventricular or ventricular-arterial connections were excluded, leaving 21 for study. The histories and clinical data of these 21 patients were obtained from the medical records. Written informed consent was obtained from the participants, and the study was approved by the Hospital Ethics Committee.

The ECHO studies were performed using a high-quality machine (EPIQ CVx Philips, Netherlands) equipped with a 3D X3-1 volumetric matrix transducer (frequency range: 2.0–4.0 MHZ) and real-time 3D (RT-3D) ultrasound imaging technology.

2D ECHO imaging

The left ventricle (LV) and LA sizes were measured, along with the LV ejection fraction (LVEF) (using Simpson’s method) and diastolic LV filling velocities, per current American Society of Echocardiography (ASE) recommendations [5]. We used the ratio between peak early (E) and late (A) filling velocities as standard indices of LV diastolic function [5].

3D ECHO imaging

The data were displayed in the live RT-3D and full volume imaging modes. 3D ECHO imaging was performed with the patient in a lateral position and monitored by electrocardiography. Imaging began with the apical 4-chamber view to observe the MV. The structure, shape and functioning of the mitral valve (MV) were observed to determine the origin and severity of MR using the parasternal long-axis and short-axis views of the LV at the level of the MV. According to the colour Doppler regurgitated jet, the severity of MR can be categorised as trivial, mild, moderate and severe. The 3D images were rotated and cropped for the 3D anatomical structure and the spatial position of the MV.

The colour Doppler quantitative technique was used to grade mitral disease according to the ASE criteria, where vena contracta (VC) of ≤ 3, <3 to > 7 and ≥ 7 mm define mild, moderate and severe MR, respectively (5).

Statistics

Continuous variables were expressed as mean ± standard deviation, and categorical variables were expressed as percentages. The normality of data distribution for continuous variables was assessed upon histogram observation and using the Kolmogorov–Smirnov test. Group comparisons were made using the Student’s t-test, ANOVA and the Mann-Whitney U and Kruskal-Wallis tests according to the normal distribution of the data and the number of independent groups. For each variable with non-normal distribution, the homogeneity of variance was assessed using Levene’s test. The distribution of continuous variables was assessed using skewness, kurtosis, visual inspection of the histogram, Q–Q plot and the Shapiro–Wilk test.

The 21 patients comprised three boys and 18 girls with a mean age and standard deviance of 13.6 ± 3.4 years (range: 6.1–17.8). The patients’ demographic characteristics are detailed in Table 1. No patients had clinical symptoms. The electrocardiogram showed sinus rhythm in all patients. Conventional ECHO (2DE) showed no associated congenital defects.

Study Population Characteristics

Real-time 3DE (RT-3DE) provides different views of the structure of an MVC, including their shape, coaptation and width, as well as the spatial position between surrounding structures. From this cohort of 21 patients identified with isolated MVCs on RT-3DE, the ECHO confirmed that the regurgitant jet originated at the site of the MVC. All the clefts reached the annular boundary. Isolated anterior leaflet clefts were detected in four patients, isolated posterior leaflet clefts in 12 patients, and both anterior and posterior clefts in five patients.

The LV dimensions and volumes were indexed according to the patients’ body surface area (BSA). No significant differences were observed between the anterior and posterior cleft groups regarding age, sex or body mass index (BMI). There were no differences in haemodynamic parameters, LV volume indexes or LV ejection fraction (LVEF) among the patients with anterior, posterior and both anterior and posterior clefts.

LVEF was in the normal range and not significantly different among all MR patients. In order to observe the relationship between the anterior/posterior cleft and VC, the ventricular strain parameters of the two groups were compared (Table 1; Fig. 1).

Table 1. Demographic and ECHO characteristics of patients with mitral valve cleft (MVC)

Patients
Sex (Female/male)	18/3
Age (year)	13.6 ± 3.4 (6.1–17.8)
BSA (m²)	1.27 ± 0.28 (0.7–1.6)
LV ejection fraction (%) EF	68.5 ± 6.9 (58–75)
LV contraction fraction (%) CF	38.5 ± 5.6 (30–51)
Mitral valve E/e’	5.28 ± 1.64 (2.69–9.9)
End diastolic volume	97.6 ± 41 (43-.217)
End diastolic volume ındex	76 ± 21 (52–136)
End systolic volume	37.9 ± 15.4 (17-.73)
End systolic volume index	25.8 ± 12.5 (9–47)
Total GLS %	22.8 ± 6.74 (10–35)
Total GCS %	29.3 ± 4.95 (14–36)
Twist^o	8.75 ± 5 (0.2–19)
Torsion	1.21 ± 0.7 (0.1–3.1)
VC (mm)	6.59 ± 1.4(4.1–9.1)

The qualitative (colour Doppler) VC of MR was higher in patients with anterior than with posterior MVCs (8.85 mm (IR 0.8; 8–9) vs. 6.64 mm (IR 0.7; 5.2–9.1, P = 0.018),

Comparison of 3D RTE measurements of MVC groups.

Global LV longitudinal strain was lower in the anterior-only MVC group − 24.7% (IR 9.8; 16.7–29%) than in the posterior-only and both-posterior-and-anterior MVC groups (–24.3% [IR 11.7; 11.5–32.6]) and − 24% [IR 17.5; 10–35]), respectively. The global circumferential strain was lower in the anterior-only MVC group (–28.9% [IR 7.5; 25–34]) and further reduced in the both-posterior-and-anterior MVC group (28.6 [IR 13.7; 14–35]). However, this did not reach statistical significance because of the small number of patients (Table 2).

Table 2

Comparison of 2D and 3D transthoracic ECHO measurements of MVC groups
Patients	Anterior cleft	Posterior	Anterior and posterior
N	4	12	5
VC (mm)	8.85 (IR 0.8; 8–9)*	6.64 (IR 0.7; 5.2–9.1)	9.4 (IR 4.7; 6.2–14)
EDVI	68 (IR 44.3; 6.2–14)	74 (IR 15.6; 52–95)	72 (IR 50; 61–136)
ESVI	26.3 (IR 17.3; 24.6–47.2)	29.4 (IR 7.05; 21–39)	26 (IR 30.3; 20–45)
3D Total GLS**	24.7 (IR 9.8; 16.7–29)	24.3 (IR 11.7; 11.5–32.6)	24 (IR 17.5; 10–35)
3D Total GCS	28.9 (IR 7.5; 25–34)	31 (IR 5.9; 27–36)	28.6 (IR 13.7; 14–35)
Torsion	9.7 (IR 0.8; 2.3–19.2)	9.4 (IR 6.6; 0.2–18.3)	6.9 (IR 3.9; 4.2–8.9)
Twist	1.35 (IR 1.7; 0.3–2.4)	1.2 (IR 0.9; 0.1–3.1)	0.9 (IR 0.3; 0.6-1)
VC: vena contracta; EDVI: end diastolic volume index; EDSV: End systolic volume index; Total GLS: total left ventricular longitudinal strain; Total GCS: total global left ventricular circumferential strain; P < 0.05 anterior vs. posterior MVC groups by Mann-Whitney U test. * P < 0.05 anterior vs. posterior MVC groups by Mann-Whitney U test.

This is the first study describing the MVCs and clinical and ECHO characteristics of children with MR. We found that the majority of isolated MVCs with significant MR were located on the posterior leaflet; there was a tendency for more severe MR in patients with isolated anterior cleft and lower left ventricular (LV) global strain values in bi-leaflet clefts.

The major aetiologies of severe MR in adult patients are degenerative or ischemic heart disease as well as rheumatic MV [6, 7]. The aetiology of MR is mostly elucidated by 2DTTE. Where this fails to reveal the mechanism/aetiology, 3DTEE is often the next diagnostic test performed because of its higher resolution, ability to image in a variety of planes, and 3D capability [8]. Previous ECHO studies have reported a low prevalence of isolated MVC, and all of these were adult studies [9]. We found a considerably higher prevalence of isolated cleft MV using 3D TTE. RT-3D images can be cropped and the valve rotated at different levels and planes while simultaneously showing the anterior and posterior leaflets in relation to the MV annulus [10].

We carefully observed the MV leaflets and found isolated anterior clefts in four patients and isolated posterior mitral clefts in 12 patients. The morphology of the MV and the cleft in the anterior leaflet have been well delineated by previous studies [11, 12]. This cleft can extend to the mitral annulus and cause severe regurgitation, but it may be only a few millimetres deep with minimal regurgitation. A similar cleft has been described in the posterior leaflet.

In this study, we found four anterior MVCs, which have been reported as rare, but 12 patients with posterior MVC, which is scarcely seen, according to recent studies [13–15]. We had overlooked these MVCs because of this discrepancy between our results and previous reports, which would indicate we are overestimating cleft-like indentations as clefts.

A cleft-like indentation is defined as a tissue defect that can be seen during systole and diastole extending at least one-half of the depth of the mitral anterior and/or posterior leaflet, especially in myxomatous MV disease [16]. In a series of patients with myxomatous MV disease, 35% had cleft‐like indentations which did not cause severe regurgitation, as with our patients in this study. Also, with the use of 3D colour Doppler, we tracked the MR jet for confirmation of origin within the cleft [17]. We think posterior MVC may not, in fact, be extremely rare (i.e. not as rare as reported) [9].

According to the adult valvular heart guidelines, asymptomatic patients with marked LV dilation and systolic dysfunction emerged as class I indications for MV surgery [2]. For children, however, there is no clear consensus, not only regarding MV surgery also regarding the intervention indications for chronic MR. In adults, a definitive diagnosis of MVC causing regurgitation needs surgery, and surgically repaired MVC usually results in survival improvement [14, 18].

The major question in an asymptomatic child with mitral moderate-to-severe regurgitation is the time allowed before determining the action to be taken. We found that left systolic functions were reduced in children with anterior MVCs and further reduced in bi-cleft MV patients, while conventional ECHO results were normal. Eventually, these children will need mitral surgery. Thus, more precise morphological views of the valve may enable better surgical planning and shorter intervention times. This is especially an issue for the visualisation and correction of MVC where there are limited 3DE resources.

Study Limitations

The patients were not randomly selected in this study because we did not forecast the results; as a result, we only included patients with moderate-to-severe MR. In future studies, mild ones might also be included. In addition, we had not performed 3D TEE for better MVC visualisation because of limited resources.

3DE for MV visualisation can be successfully implemented in children. Anterior and bi-leaflet mitral clefts may result in severe regurgitation and can cause early systolic dysfunction. Diagnosis of MVC can help management plans (including surgery) before irreversible cardiac dysfunction. 3DE should be proposed during follow-up.

Compliance with Ethical Statements

Conflict of Interest: Author declares that they have no conflicts of interest to disclose.

Funding: There is no funding source

Ethical approval: Informed consent was obtained from the parents or legal guardians of all individual participants included in the study.

Acknowledgements: We thank Associated Prof. Dr. Reyhan Dedeoglu for her assistance in the strain measurements and 3D image acquisitions for this study.

Authors’ Contributions: All three authors contributed to the design and data analysis and critically read the final manuscript.

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No competing interests reported.

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published 05 Apr, 2023

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Editorial decision: Major revision
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You are reading this latest preprint version

Revealing mitral valve cleft using real-time 3-dimensional echocardiography in children with mitral regurgitation

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Abstract

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Introduction

Methods

Statistics

Results

Study Population Characteristics

Discussion

Study Limitations

Conclusion

Declarations

References

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