Characteristics and clinical implication of mitral annular disjunction in apparently normal hearts: a cardiac magnetic resonance study

Introduction

Background

Mitral annular disjunction (MAD) is a separation between the atrial wall-mitral valve junction and the left ventricular (LV) attachment (1). First described by Henle in 1876 (2), MAD has since been recognized as being associated with mitral valve prolapse (MVP) (3). Over the years, increasing evidence from multiple imaging modalities has demonstrated associations among MAD, MVP, and ventricular arrhythmia (VA) (4-10).

Rationale and knowledge gap

However, in patients with valvular heart diseases, coexisted LV myocardial fibrosis has also been detected using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) (4,6,8). As LV myocardial fibrosis is also closely associated with VA (11), it complicates the relationship between MAD and VA in these patients. Interestingly, recent studies have indicated that MAD can also occur in structurally normal hearts (12,13). Toh et al. reported an incidence of 96% for MAD in structurally normal hearts, utilizing computed tomography for their analysis (13). In a study with a large population cohort, Zugwitz et al. demonstrated that MAD was commonly observed in cine images derived from cardiac magnetic resonance (CMR) (12). Thus far, there have been no studies reported in the literature that incorporate LGE imaging to investigate MAD in subjects with normal CMR findings. Given that MAD can occur in both symptomatic patients and the general population, it is imperative to clarify its relationship with adverse cardiovascular outcomes, such as VA. A comprehensive evaluation of hearts with normal morphology and myocardial tissue characterization may provide valuable insights into the characteristics, clinical implications and associated risk stratification of MAD.

Objective

Therefore, our study aims to assess the incidence and characteristics of MAD in apparently normal hearts confirmed by comprehensive CMR including LGE sequence, and to explore its impact on myocardial contraction and potential association with VA. We present this article in accordance with the STROBE reporting checklist (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2024-673/rc).

Methods

Study population

In this retrospective cohort study, we consecutively screened 449 cases with possible apparently normal hearts (ANH) as previously assessed by CMR, from both outpatient and inpatient individuals at a tertiary care center between January 2017 and March 2023. Possible ANH was identified based on CMR reports indicating structurally and functionally normal hearts on cine images, with no evidence of delayed enhancement on LGE images. The identification of MAD was determined by two radiologists (Y.H.Y., with 2 years of CMR experience; L.L.W., with 1 year of CMR experience) with specifical trainings. Additionally, we included 92 patients with isolated MVP as a control group, defined by CMR as that the displacement of one or both mitral leaflets ≥2 mm into the left atrium during systole in the LV outflow tract long-axis view, without any other structural abnormalities on CMR examination (8,14). The exclusion criteria were as follows: (I) poor image quality; (II) incomplete image sequence; (III) additional abnormalities detected by CMR during the screening process; (IV) lost to follow-up. As a result, 374 cases in the ANH group and 70 cases in the MVP group were included in the final analysis (Figure 1). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Board of Beijing Anzhen Hospital (No. 2024245x) and individual consent for this retrospective analysis was waived.

Figure 1 Study flowchart. CMR, cardiac magnetic resonance; MVP, mitral annular prolapse; MAD, mitral annular disjunction.

Demographic characteristics and medical history were collected from an electronic medical record database. VA included premature ventricular complex, non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (VT) and ventricular fibrillation (VF). The history of VA, including premature ventricular complex (a premature QRS complex typically ≥120 ms in duration with a broad T-wave opposite the QRS deflection and no preceding P-wave), NSVT (≥3 consecutive ventricular beats at a rate of ≥120 bpm and <30 s in duration), VT (≥3 consecutive ventricular beats at a rate of ≥120 bpm and >30 s in duration) and VF [a chaotic rhythm with undulations and no discrete QRS complexes on the surface electrocardiogram (ECG)] (15), was recorded from medical history, ECG or 24-h Holter.

CMR imaging

All CMR examinations were performed on 3.0 T scanners (Discovery MR750, GE medical systems, Milwaukee, USA; MAGNETOM Siemens Verio, Siemens Health Care, Erlangen, Germany; Ingenia, Philips Healthcare, Best, Netherlands) using standardized cardiac protocols with electrocardiographic and respiratory gating. The standard CMR protocol mainly consisted of (I) LV short-axis (multi-slice full coverage of the LV) and long-axis (two-chamber, three-chamber, and four-chamber views) cine images acquired by a balanced steady-state free precession sequence; (II) LGE images obtained by a phase-sensitive inversion-recovery sequence in views identical to cine images, which were performed 10–15 min after the intravenous administration of a 0.2 mmol/kg gadolinium-based contrast agent (Gadopentetate dimeglumine, Magnevist, Bayer Schering, Germany). Additional information of CMR scan acquisition information is detailed in Table S1.

Image analysis

Image analysis was independently conducted by two radiologists blinded to all clinical data. MAD was defined as the presence of a longitudinal displacement measuring ≥1 mm at end-systole (16) on long-axis cine images. Using standardized myocardial segmentation nomenclature, the disjunction involving the posterior leaflet of the mitral valve was categorized based on its extension on long-axis cine images. Specifically, the disjunction extending to the anterior or anterolateral segments in two- or four- chamber views was classified as the P1 scallop, to the inferolateral segment in three-chamber views as the P2 scallop, and to the inferior segment in two-chamber views as the P3 scallop, respectively (Figure 2) (5,13,17).

Figure 2 MAD-affected segment distribution and longitudinal length measurement using CMR. (A) A schematic diagram of the mitral valvar orifice, the atrioventricular junction area and its corresponding posterior leaflet: P1 scallop (anterior to antero-lateral segment), P2 scallop (infero-lateral segment), P3 (inferior segment). (B) The planning methods with corresponding imaging planes used for assessment of MAD. Standardized myocardial segmentation nomenclature is used to obtain corresponding three long-axis views (b2-b4) from CMR short-axis view (b1). Arrows point to the respective different disjunction sites of the mitral valve posterior leaflet: P1 scallop (orange arrow), P2 scallop (blue arrow), P3 scallop (green arrow). (C) The measurement of longitudinal MAD on 2-chamber long-axis view. The orange bidirectional arrow is the distance of P1 scallop disjunction, the green bidirectional arrow is the distance of P3 scallop disjunction. CMR, cardiac magnetic resonance; MAD, mitral annular disjunction.

Cardiac function and myocardial strain were measured using a commercially available post-processing software (cvi42, version 5.10, Circle Cardiovascular Imaging, Calgary, Canada). LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV), LV mass, left atrial maximum volume (LAV_max) and minimum volume (LAV_min) were quantified on cine images according to the current guideline (18), and then indexed to body surface area (BSA) except for LVEF. To measure LV strain, the LV endocardial and epicardial contours were automatically traced on the short-axis, two- and four-chamber long-axis cine images at end-diastole throughout the cardiac cycle. Manual corrections were performed where necessary to ensure optimal tracking. The LV strain parameters calculated included global longitudinal strain (GLS) and global circumferential strain (GCS). The left arial (LA) endocardial and epicardial borders were manually delineated, excluding the pulmonary veins and LA appendage. After automatic tracking throughout the entire cardiac cycle, total strain (εs) was then derived. Active strain (εa) and passive strain (εe) were measured on two- and four-chamber long-axis cine images during the LA systolic and diastatic phases, respectively. Strain rates were calculated by dividing the respective strain values by the corresponding time intervals.

Clinical follow-up

The primary endpoint was a composite of sudden cardiac deaths (SCD), aborted SCD, ablation therapy for VA, and the implantation of an implantable cardioverter-defibrillator (ICD). A comprehensive follow-up was conducted on two cohorts: the ANH group and the MVP group. All observed outcomes were adjudicated by two physicians (H.B.Z., with 4 years of CMR experience; G.Y.L., with 5 years of CMR experience) blinded to the CMR data, utilizing a combination of medical records, clinical evaluations, and telephonic interviews for confirmation.

Intra-observer and inter-observer reproducibility

Intra- and inter-observer variability for LV functional parameters, LV and LA strain measurements, and disjunction distances were assessed by analyzing 40 randomly selected cases with positive MAD. One observer (Y.H.Y.) measured twice at least 1 month apart, and a second observer (Z.H.L., with 3 years of CMR experience), blinded to the first observer’s results, performed an additional measurement. The intraclass correlation coefficient (ICC) was used to evaluate reliability. An ICC >0.90 indicates excellent reliability, >0.75–0.90 indicates good reliability, 0.50–0.75 indicates moderate reliability, and <0.50 indicates poor reliability.

Statistical analysis

Normality was assessed using the Shapiro-Wilk test. Continuous variables were expressed as means ± standard deviations or medians and interquartile ranges (IQRs), and categorical variables as frequencies and percentages. Group comparisons for continuous data were performed using the two-sample t-test or Wilcoxon rank-sum test, while categorical data were compared using Pearson’s Chi-squared test or Fisher’s exact test. The correlation between MAD and other parameters was evaluated using Pearson or Spearman correlation coefficients. Univariable logistic regression analysis [odds ratios (ORs) and 95% confidence intervals (CIs)] was utilized to identify the variables related to MAD and VA, respectively. Univariable factors with a P value less than 0.1 were entered into the backward elimination multivariable analysis. To explore the associations between variables and MAD (or VA), the variance inflation factor (VIF) was measured for all selected variables and used to assess collinearity collectively. The VIF ≥3 was considered indicative of multicollinearity among variables in this study. Variables that contributed to an overall VIF ≥3 were excluded from the multivariate analysis to maintain the accuracy and stability of the regression coefficients. All statistical analyses were conducted with SPSS version 24.0 (SPSS Inc., Chicago Illinois). Two-sided P values <0.05 were considered significant.

Results

Study population

The final analysis included 374 ANH individuals [185 female (49.5%)] with an average age of 35.5±16.1 years (range, 9–76 years) and 70 isolated MVP individuals [30 female (42.8%)] with an average age of 49.5±14.5 years (range, 12–75 years). Individuals were subdivided the presence of MAD into those with MAD (MAD+) and those without MAD (MAD−). MAD+ subjects were more likely to be female (ANH: 55.5% vs. 44.8%, P=0.04; MVP: 51.3% vs. 32.3%, P=0.02) compared to MAD− subjects, and showed a higher prevalence of VA (ANH: 45.7% vs. 26.6%, P=0.001; MVP: 53.8% vs. 29.0%, P=0.03). In the ANH group, MAD+ subjects were significantly younger than MAD− subjects (32.3±16.2 vs. 37.1±15.9 years, P=0.04), whereas no statistically significant difference was found in the MVP group (46.5±14.4 vs. 53.3±14.1 years, P=0.052). Detailed baseline demographic and clinical characteristics of the ANH group and the MVP group are listed in Table 1 and Table S2, respectively.

The most common indications for CMR examinations in the ANH group were chest tightness (30.5%), palpitations (28.1%), evaluation for documented arrythmia (14.7%) (Table S3). Subsequent clinical assessments revealed that 17 subjects (4.5%) experienced syncope and 131 subjects (35.0%) had symptomatic VA in the ANH group. In contrast, in the MVP group, eight subjects (11.4%) experienced syncope and 30 subjects (42.9%) had symptomatic VA before CMR examination (Table S2).

The presence and characteristics of MAD

The prevalence of MAD was lower in the ANH group compared to the MVP group (43.9% vs. 55.7%, P=0.06). The average distance of disjunction was 2.8±1.3 mm (range, 1.7–13.5 mm) in the ANH group and 2.9±1.4 mm (range, 1.7–9.7 mm) in the MVP group, respectively, with no statistically significant difference observed between the two groups (P=0.37). The distribution of disjunction varied considerably across segments in both groups. The majority of MAD occurred at the P3 scallop (ANH: 41.7%; MVP: 54.3%), followed by the P1 scallop (ANH: 13.9%, with 7.4% in the anterior segment and 6.5% in the antero-lateral segment; MVP: 15.7%, with 9.3% in the anterior segment and 6.4% in the antero-lateral segment), with the P2 scallop being at least involved (ANH: 2.7%; MVP: 10.0%). Notably, MAD was significantly less prevalent at the P2 and P3 scallops in the ANH group compared to the MVP group (P2: 2.7% vs. 10.0%, P=0.02; P3: 41.7% vs. 54.3%, P=0.001). The prevalence of MAD at the P1 scallop, however, showed no significant difference between the ANH and MVP groups (Table 2). In addition, the disjunction distances also showed no significant differences across three scallops, as detailed in Table 2.

Associations of clinical and CMR variables with MAD

In the ANH group, no statistically significant difference was observed in the LA and LV functional parameters between the MAD+ and MAD− subgroups. For LA and LV strain parameters, only peak positive strain rate (SRs) was significantly lower in MAD+ subjects compared to MAD− subjects (1.6±0.5 vs. 1.8±0.8 s⁻¹, P=0.03). Detailed measurements of CMR parameters in the ANH group are shown in Table 1. Furthermore, the comparison of cardiac strain parameters among different sites of the posterior mitral valve leaflet between MAD+ and MAD− subjects in the ANH group was shown in Table S4. Only the P3 disjunction exhibited lower SRs (1.6±0.5 vs. 1.8±0.7 s⁻¹, P=0.02), whereas no such differences were observed at the P1 and P2 scallops.

Univariate logistic regression analysis showed that age, female sex, VA and SRs were associated with MAD. In multivariate analysis, VA and female sex remained independently associated with MAD (OR: 3.33, 95% CI: 2.21–5.52, P=0.001; OR: 1.64, 95% CI: 1.05–2.56, P=0.03) (Table 3).

Associations of clinical and CMR variables with VA

Table 4 presents the comparison of disjunction presence and distance between individuals with and without VA in the ANH group. MAD was more prevalent in ANH subjects with VA than in those without VA (61.2% vs. 34.2%, P=0.001), particularly at the P2 (5.2% vs. 1.3%, P=0.04) and P3 scallops (60.4% vs. 32.9%, P=0.001), but not at the P1 scallop (14.9% vs. 13.3%, P=0.23). Furthermore, disjunction distances at the P2 scallop were significantly longer in subjects with VA than those without VA (3.1±1.1 vs. 2.2±1.5 mm, P=0.006). However, no such difference was observed at the P1 and P3 scallops (P1: 2.2±0.6 vs. 2.2±0.6 mm, P=0.65; P3: 2.7±0.9 vs. 2.2±1.1 mm, P=0.12). Additionally, subjects with VA exhibited lower peak early negative strain rate (SRe) compared to those without VA (−1.6±0.8 vs. −1.9±0.7 s⁻¹, P=0.007), as presented in Table S5. There were no statistically significant differences in other strain parameters between ANH patients with and without VA.

Univariate logistic regression analysis showed that LA ejection fraction, LV cardiac output, εs and εa, all LA strain rates, the presence of MAD and the disjunction distance at any site were associated with an increased incidence of VA (Table 5). εs and εa were excluded from the multivariable analysis because their inclusion resulted in an overall VIF of 5.1 and 5.7 respectively, exceeding the acceptable threshold of multicollinearity. Due to VIF values greater than 3 when both the presence and distance of disjunction at the same sites were included (P1: VIF =9.7; P2: VIF =5.9; P3: VIF =7.5), we constructed two separate models to analyze the presence and distance of disjunction respectively. Model 1 incorporated variables with a P-value less than 0.1 from the univariate analysis and the three disjunction sites, while Model 2 included variables with a P-value less than 0.1 from the univariate analysis and the three disjunction distances. Subsequently, multivariate analysis demonstrated that only the presence and distance of MAD at the P2 scallop were independently associated with VA in the ANH group, with ORs of 2.72 (95% CI: 1.69–4.36; P=0.01) and 1.47 (95% CI: 1.05–2.05; P=0.01) respectively. Neither P1 nor P3 disjunction showed a significant association.

Associations between MAD and primary endpoints

The median follow-up duration was 52 months (IQR, 28–64 months) after the initial CMR examinations. During the follow-up, two patients (0.5%) in the ANH group underwent ablation therapy for recurrent NSVT, with no cases of SCD. In the MVP group, five patients (7.1%) received ICD therapy for VA, and one patient (1.4%) died from VF. Of the eight patients who experienced primary outcomes, only one from the MVP group received ICD therapy without MAD, while all others who reached the primary endpoint had MAD. Due to the low number of patients with primary outcome events, no further analysis could be done.

Intra-observer and inter-observer reproducibility

LV functional parameters, LV and LA strain measurements, as well as disjunction lengths were reproducible at both intra- and inter-observer levels. The ICCs for these measurements are summarized in Table S6. Intra-observer reliability was excellent, with ICCs of 0.91 or higher for all measurements. Inter-observer reliability was good to excellent, with SRs showing the highest reproducibility, indicated by an ICC of 0.96.

Discussion

In this study, we investigated MAD in patients with normal cardiac morphology, function and myocardium assessed by CMR, providing new insights into this entity. The important finding was that MAD was more commonly observed at both the P1 and P3 scallops and showed shorter distances. In contrast, MAD at the P2 scallop was infrequent, tended to be longer and was associated with VA, independent of the presence of myocardial fibrosis. In addition, both VA and female sex were associated with the presence of MAD, while myocardial contractility showed no significant correlation with MAD in individuals with normal hearts assessed by CMR.

Prevalence and characteristics of MAD

The reported prevalence of MAD varies from 7.2% to 96.0%, across different cohorts because of the varied thresholds used for defining disjunction and different assessment methods (1,13,19,20). In this CMR study, using a threshold of 1mm, we identified a 43.9% prevalence of MAD in a cohort with normal hearts, which is lower compared to cohorts with valvular heart diseases. Consistent with previous studies, MAD was more commonly observed in women and younger subjects (5,19,21), although the clinical implication of this MAD phenotype remains undetermined. Anatomically, the posterior mitral annulus ring is a discontinuous fibrous connective tissue band (22). In our study, MAD was most commonly observed at the P1 and P3 scallops, with infrequent occurrence at the P2 scallop. This near-bimodal distribution was consistent across both normal hearts and MVP patients, aligning with findings from previous studies involving diseased or general cohorts (5,12,13). Furthermore, the reported disjunction distance varies from 1 to 13 mm across different cohorts and imaging methods (3,5,7,19-21). The average disjunction distance in the normal heart cohort in the present study was 2.8 mm, closely aligning with previous findings in structurally normal hearts assessed by CT (13) and the general population assessed by CMR (12). Previous studies have demonstrated that the longitudinal MAD length varies around the mitral annulus (5,12,13,19,20). In our study, although disjunction at the P2 scallop was less frequent, it was longer compared to that at the P1 and P3 scallops, in both individuals with normal hearts and those with MVP.

Impact of MAD on myocardial contraction

MAD results in a displacement of the mitral annulus toward the atrial side, contributing to hypermobility of the atrioventricular junction and augmented myocardial stretch (1). In an echocardiographic study, despite preserved LVEF, impaired cardiac strain parameters were observed in MVP patients with MAD (23). The impact of MAD on myocardial contractility in general population remains unclear. In our cohort of individuals with normal hearts assessed by CMR, LA and LV function were comparable between subjects with and without MAD. Additionally, LV and most LA strain parameters did not show significant differences between two groups, except for SRs at the P3 scallop. Furthermore, multivariate analysis revealed that no significant association was found between cardiac strain parameters and the presence of MAD. In subjects with normal hearts, shorter disjunction did not seem to significantly affect early myocardial contractility. Further investigation is required to elucidate the relationship between disjunction distance and myocardial contraction.

MAD and its relation to VA

MAD is commonly observed in MVP patients and is independently associated with arrhythmic events (21), particularly in cases of arrhythmic MVP (24). Carmo et al. used echocardiography to assess MAD in MVP patients and identified a threshold of 8.5 mm to predict the risk of VA (3). A recent meta-analysis of investigating the relationship between MAD and VA has demonstrated that MAD is associated with a higher risk of VA in patients with MVP. Specifically, MAD, along with LGE, T-wave inversion, and bileaflet prolapse, has been identified as a characteristic marker for the occurrence of VA in this patient population (25). However, arrhythmias were also found in patients with MAD but without MVP, suggesting that MAD itself may carry an arrhythmic risk (5). Our findings support this viewpoint, as the patients with normal hearts who experienced VA had a higher presence of MAD. Moreover, MAD at the P2 scallop and its distance were independently associated with VA, each 1 mm increase in the length of MAD at the P2 scallop was associated with a 1.47-fold increase in the risk of VA (95% CI: 1.05–2.05, P=0.01). Although the incidence is low according to its bimodal distribution, MAD at the P2 scallop is related to VA, warrants further investigation when identified.

Myocardial fibrosis has been recognized as an important mechanism for arrhythmias (26). Previous studies reported that coexisting MAD and LV myocardial fibrosis were associated with VA (4,5,21). Disjunction-related hypermobility of the atrioventricular junction can increase myocardial stretch, leading to mechanical injury of the ventricular myocardium and the development of replacement fibrosis (4). Some researchers have proposed that the chronic mechanical stress induced by MAD may lead to a stress response in the LV papillary muscles, subsequently triggering myocardial inflammation, fibroblast proliferation, and fibrotic deposition, which may serve as a substrate for VA (25). Scheirlynck et al. found that in patients with MVP and MAD, transforming growth factor-beta interacts with mutated Filamin genes, promoting myxomatous degeneration of the mitral valve. This process accelerates the development of myocardial fibrosis, thereby increasing the risk of VA (27). In the present study, before the development of myocardial fibrosis detected by LGE, we found that both the presence of P2 disjunction and its distance are independently associated with VA. This may be associated with several electrophysiological mechanisms. Firstly, MAD in the inferolateral wall can induce localized mechanical tension on the myocardium, altering the depolarization and repolarization processes of myocardial cells, leading to instability in local electrical activity and thereby increasing the risk of VA. Additionally, the electrical conduction delay in the inferolateral region further exacerbates the irregularity of the cardiac electrical activity, promoting ectopic excitation and the occurrence of arrhythmias (5,28). These findings encourage further exploration of other potential mechanisms underlying MAD-related VA, and may provide a new risk factor for VA, particularly in patients with apparently idiopathic VA. The causal relationship between MAD and VA remains unclear, and further investigation is warranted to elucidate the role of disjunction in cardiac electrical function.

Clinical implications

The major controversies of MAD are its prevalence and potential clinical significance in people with normal hearts, both of which are crucial for determining whether disjunction is a pathological finding. Our findings indicate that MAD is commonly observed in apparently normal heart subjects, typically involving the P1 and P3 scallops with minimal disjunction length, consistent with previous studies (12,13). Disjunction at the P1 and P3 scallops has no association with VA and may represent a normal anatomical variation. In contrast, although P2 disjunction is infrequent in normal heart subjects, both the prevalence and distance of MAD at this site were associated with VA. No deaths were reported in this normal heart cohort during the follow-up, and MAD was not associated with mortality, which is in line with a previous study (21). Notably, in a large general cohort study, although the incidence of MAD was high, the reported incidence of arrhythmic events was significantly lower compared to our findings (VA: 35.0%). A potential explanation for this discrepancy is the difference in study populations: the former study primarily involved healthy individuals, while our study included symptomatic patients. Based on previous studies (3,5) and our findings, further investigation may be warranted for patients with P2 disjunction, particularly when arrhythmic symptoms are present.

Limitations

Several limitations of this study should be acknowledged. The single-center retrospective design limits the ability to minimize selective bias. Second, only standard LV long-axis cine images were available, and further studies may need to acquire more long-axis cine images with extra interslice rotation to better assess the circumferential extent of the mitral annulus in MAD. Third, the relatively short follow-up period may limit a comprehensive understanding of the clinical implications of MAD. Fourth, disjunctions smaller than 1 mm were not evaluated in this study, potentially leading to an underestimation of the prevalence of MAD. Finally, the ANH cohort was referred for CMR imaging partly due to symptoms such as VA. As the exact proportion of these cases cannot be quantified, this referral bias may have influenced the observed prevalence of MAD and its association with VA.

Conclusions

MAD is a common finding in individuals with apparently normal heart. Although P2 disjunction is relatively rare, it is independently associated with VA in individuals with normal hearts and without myocardial fibrosis. Therefore, recognizing P2 disjunction and providing appropriate management are important for patients with symptomatic VA. Further longitudinal studies are needed to clarify the mechanisms linking MAD to VA, and to enhance the understanding of clinical significance of MAD.

Acknowledgments

We would like to thank Dr. Jie Huang for helping to improve the English.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2024-673/rc

Data Sharing Statement: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2024-673/dss

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2024-673/prf

Funding: This study was supported by the Beijing Natural Science Foundation (Grant No. 7222302), the National Natural Science Foundation of China (Grant No. 82071875) and the National Key Research and Development Program of China (Project No. 2021YFF0501400).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2024-673/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Board of Beijing Anzhen Hospital (No. 2024245x) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Hutchins GM, Moore GW, Skoog DK. The association of floppy mitral valve with disjunction of the mitral annulus fibrosus. N Engl J Med 1986;314:535-40. [Crossref] [PubMed]
2. Henle J. Handbuch der systematischen Anatomie des Menschen. Vieweg; 1876.
3. Carmo P, Andrade MJ, Aguiar C, et al. Mitral annular disjunction in myxomatous mitral valve disease: a relevant abnormality recognizable by transthoracic echocardiography. Cardiovasc Ultrasound 2010;8:53. [Crossref] [PubMed]
4. Perazzolo Marra M, Basso C, De Lazzari M, et al. Morphofunctional Abnormalities of Mitral Annulus and Arrhythmic Mitral Valve Prolapse. Circ Cardiovasc Imaging 2016;9:e005030. [Crossref] [PubMed]
5. Dejgaard LA, Skjølsvik ET, Lie ØH, et al. The Mitral Annulus Disjunction Arrhythmic Syndrome. J Am Coll Cardiol 2018;72:1600-9. [Crossref] [PubMed]
6. Perazzolo Marra M, Cecere A, Cipriani A, et al. Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse. JACC Clin Electrophysiol 2024;10:670-81. [Crossref] [PubMed]
7. Essayagh B, Iacuzio L, Civaia F, et al. Usefulness of 3-Tesla Cardiac Magnetic Resonance to Detect Mitral Annular Disjunction in Patients With Mitral Valve Prolapse. Am J Cardiol 2019;124:1725-30. [Crossref] [PubMed]
8. Figliozzi S, Georgiopoulos G, Lopes PM, et al. Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse. Radiology 2023;306:112-21. [Crossref] [PubMed]
9. Esposito A, Gatti M, Trivieri MG, et al. Imaging for the assessment of the arrhythmogenic potential of mitral valve prolapse. Eur Radiol 2024;34:4243-60. [Crossref] [PubMed]
10. Vriz O, Eltayeb A, Landi I, et al. Transthoracic echocardiography for arrhythmic mitral valve prolapse: Phenotypic characterization as first step. Echocardiography 2022;39:1158-70. [Crossref] [PubMed]
11. Mavrogeni S, Petrou E, Kolovou G, et al. Prediction of ventricular arrhythmias using cardiovascular magnetic resonance. Eur Heart J Cardiovasc Imaging 2013;14:518-25. [Crossref] [PubMed]
12. Zugwitz D, Fung K, Aung N, et al. Mitral Annular Disjunction Assessed Using CMR Imaging: Insights From the UK Biobank Population Study. JACC Cardiovasc Imaging 2022;15:1856-66. [Crossref] [PubMed]
13. Toh H, Mori S, Izawa Y, et al. Prevalence and extent of mitral annular disjunction in structurally normal hearts: comprehensive 3D analysis using cardiac computed tomography. Eur Heart J Cardiovasc Imaging 2021;22:614-22. [Crossref] [PubMed]
14. Han Y, Peters DC, Salton CJ, et al. Cardiovascular magnetic resonance characterization of mitral valve prolapse. JACC Cardiovasc Imaging 2008;1:294-303. [Crossref] [PubMed]
15. Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 2022;43:3997-4126. [Crossref] [PubMed]
16. Garg P, Swift AJ, Zhong L, et al. Assessment of mitral valve regurgitation by cardiovascular magnetic resonance imaging. Nat Rev Cardiol 2020;17:298-312. [Crossref] [PubMed]
17. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539-42. [Crossref] [PubMed]
18. Schulz-Menger J, Bluemke DA, Bremerich J, et al. Standardized image interpretation and post-processing in cardiovascular magnetic resonance - 2020 update: Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing. J Cardiovasc Magn Reson 2020;22:19. [Crossref] [PubMed]
19. Konda T, Tani T, Suganuma N, et al. The analysis of mitral annular disjunction detected by echocardiography and comparison with previously reported pathological data. J Echocardiogr 2017;15:176-85. [Crossref] [PubMed]
20. Lee AP, Jin CN, Fan Y, et al. Functional Implication of Mitral Annular Disjunction in Mitral Valve Prolapse: A Quantitative Dynamic 3D Echocardiographic Study. JACC Cardiovasc Imaging 2017;10:1424-33. [Crossref] [PubMed]
21. Essayagh B, Sabbag A, Antoine C, et al. The Mitral Annular Disjunction of Mitral Valve Prolapse: Presentation and Outcome. JACC Cardiovasc Imaging 2021;14:2073-87. [Crossref] [PubMed]
22. Silbiger JJ. Anatomy, mechanics, and pathophysiology of the mitral annulus. Am Heart J 2012;164:163-76. [Crossref] [PubMed]
23. Özyıldırım S, Guven B, Yumuk MT, et al. Evaluation of left ventricular function in patients with mitral annular disjunction using speckle tracking echocardiography. Echocardiography 2024;41:e15813. [Crossref] [PubMed]
24. Essayagh B, Sabbag A, El-Am E, et al. Arrhythmic mitral valve prolapse and mitral annular disjunction: pathophysiology, risk stratification, and management. Eur Heart J 2023;44:3121-35. [Crossref] [PubMed]
25. Pistelli L, Vetta G, Parlavecchio A, et al. Arrhythmic risk profile in mitral valve prolapse: A systematic review and metanalysis of 1715 patients. J Cardiovasc Electrophysiol 2024;35:290-300. [Crossref] [PubMed]
26. Tison GH, Abreau S, Barrios J, et al. Identifying Mitral Valve Prolapse at Risk for Arrhythmias and Fibrosis From Electrocardiograms Using Deep Learning. JACC Adv 2023;2:100446. [Crossref] [PubMed]
27. Scheirlynck E, Dejgaard LA, Skjølsvik E, et al. Increased levels of sST2 in patients with mitral annulus disjunction and ventricular arrhythmias. Open Heart 2019;6:e001016. [Crossref] [PubMed]
28. Chakrabarti AK, Bogun F, Liang JJ. Arrhythmic Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical Features, Pathophysiology, Risk Stratification, and Management. J Cardiovasc Dev Dis 2022;9:61. [Crossref] [PubMed]