Mitral Valve Prolapse Patients Research Articles

Arrhythmic Mitral Valve Prolapse: A Comprehensive Review.

Mitral valve prolapse (MVP) is a prevalent cardiac disorder that impacts approximately 2% to 3% of the overall population. While most patients experience a benign clinical course, there is evidence suggesting that a subgroup of MVP patients face an increased risk of sudden cardiac death (SCD). Although a conclusive causal link between MVP and SCD remains to be firmly established, various factors have been associated with arrhythmic mitral valve prolapse (AMVP). This study aims to provide a comprehensive review encompassing the historical background, epidemiology, pathology, clinical manifestations, electrocardiogram (ECG) findings, and treatment of AMVP patients. A key focus is on utilizing multimodal imaging techniques to accurately diagnose AMVP and to highlight the role of mitral annular disjunction (MAD) in AMVP.

Are children with mitral valve prolapse more anxious?

Mitral valve prolapse (MVP) is a common valvular disease in children. Symptoms in children with MVP are not explained by the severity of mitral regurgitation alone. Hence, we sought to correlate symptom status with the incidence of anxiety disorder in this population. Groups were as follows: (a) MVP; n = 115; mean age: 13.5 ± 3.06 years and (b) control; n = 53; mean age: 15.1 ± 13.2. The Screen for Child Anxiety-Related Emotional Disorders (SCAREDs) scale was filled by all participants. The SCARED scores of 25 and above determined a warning for anxiety disorders. The mean SCARED scale values of MVP and control groups were 29.2 ± 13.08 and 24.9 ± 14.17, respectively (P = 0.065). Although the SCARED scale score was higher among the MVP patients, no significant difference was found between the groups in terms of the mean SCARED score, or the number of participants with a score of 25 or more. While girls with MVP had higher anxiety scores compared to boys with the disorder, there was no difference with respect to SCARED scores in children with MVP and the general population when analyzed separately by gender. Moreover, the SCARED scale score was significantly higher in symptomatic MVP patients than in asymptomatic cases. Children with MVP did not have higher anxiety scores compared to those without the syndrome. However, MVP patients with higher anxiety scores may benefit from a psychiatric assessment since higher scores correlate with symptoms.

Effectiveness of the risk stratification proposed by the 2022 European Heart Rhythm Association Expert Consensus statement on arrhythmic mitral valve prolapse

Recently, an expert consensus statement proposed indications where implantation of a primary prevention implantable cardioverter-defibrillator (ICD) may be reasonable in patients with mitral valve prolapse (MVP). The objective was to evaluate the proposed risk stratification by the expert consensus statement. Consecutive patients with MVP without alternative arrhythmic substrates with cardiac magnetic resonance imaging (CMR) were included in a single-center retrospective registry. Arrhythmic MVP (AMVP) was defined as a total premature ventricular complex burden ≥5%, non-sustained ventricular tachycardia (VT), VT, or ventricular fibrillation. The end point was a composite of SCD, VT, inducible VT, and appropriate ICD shocks. In total, 169 patients (52.1% male, median age 51.4 years) were included and 99 (58.6%) were classified as AMVP. Multivariate logistic regression identified the presence of late gadolinium enhancement (OR 2.82, 95%CI 1.45-5.50) and mitral annular disjunction (OR 1.98, 95%CI 1.02-3.86) as only predictors of AMVP. According to the EHRA risk stratification, 5 patients with AMVP (5.1%) had a secondary prevention ICD indication, while in 69 patients (69.7%) the implantation of an ICD may be reasonable. During a median follow-up of 8.0 years (IQR 5.0-15.6), the incidence rate for the composite arrhythmic end point was 0.3%/year (95%CI 0.1-0.8). More than half of MVP patients referred for CMR met the AMVP diagnostic criteria. Despite low long-term event rates, in 70% of patients with AMVP the implantation of an ICD may be reasonable. Risk stratification of SCD in MVP remains an important knowledge gap and requires urgent investigation.

Abstract P2100: Highly Localized Myocardial Expression Of Brain Natriuretic Peptide In Patients With Mitral Valve Prolapse

Mitral valve prolapse (MVP) is a common cause of mitral regurgitation (MR), adverse left ventricular (LV) remodeling and arrhythmias. MVP induces mechanical stretch to the inferobasal (INF) myocardium and papillary muscles. The underlying regional and molecular pathology of MVP-induced LV remodeling remains incompletely understood. The aim was to characterize the molecular effects of mechanical stretch by comparing the regional gene expression of the INF region of LV in patients with MVP. Biopsies were obtained from the INF LV and the interventricular septum during mitral valve repair surgery for MVP-induced primary MR. Spatial transcriptome sequencing results correlated with histological staining of fibrosis in the INF and septal regions (R=0.97, P<0.0001). The extent of fibrosis was similar between the INF region and the septal control in the respective patients with MVP. The localized fibrotic areas of the INF region showed decreased expression of cardiac myocyte genes and increased expression of fibrous and EndMT markers. In the INF region, we identified a transition zone between healthy myocardium and fibrous tissue. This transition zone showed increased expression of the NPPB gene encoding brain natriuretic peptide (BNP), whereas NPPB was not increased in the septal region of the same patients, and was confirmed by qPCR (NPPB +6.4-fold, N=11, P=0.004). The INF border zone is characterized by increase expression of NPPB, IGFBP2 and MFGE8, which have been described to be associated with adverse LV remodeling in heart failure. The serum NT-proBNP levels (mean 276.8 ± 121.6 pg/ml) of the patients correlated with NPPB levels from the INF region (R=0.76, P=0.01, N=9), whereas no correlation was found with NPPB levels from the septal control regions (R=0.17, P=0.65) of the same patients. In conclusion, spatial transcriptome analysis in MVP patients identifies a transition zone of the INF region of LV which is exposed to high mechanical stretch. This localized transition zone has a specific gene expression profile, e.g. with increased NBBP expression that correlates with increased NT-ProBNP serum concentrations. Our results indicate that mechanical stretch induces highly localized myocardial pathologies with systemic consequences.

Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi)>.7mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. Of the 94 patients with MVP and significant MR, 31 patients showed a TVi>.7mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.

MİTRAL KAPAK PROLAPSUSU OLAN ÇOCUKLARDA KARDİYAK OTONOMİK DİSFONKSİYONUN VE ARİTMİ RİSKİNİN DEĞERLENDİRİLMESİ

Objective: The occurrence of symptoms in patients with mitral valve prolapse (MVP) is linked to autonomic dysfunction and neuroendocrine causes rather than progressive mitral valve insufficiency. The goal was to assess the risk of autonomic dysfunction and arrhythmia in patients with MVP.
 Methods: The study included 63 patients with primary MVP and a control group of 64 children of similar age and gender. Following a physical examination, all patients' histories were taken, and 12-lead ECGs, autonomic function tests, echocardiography, and 24-hour Holter rhythm studies were performed.
 Results: The patient group had a higher mean resting heart rate than the control group. Orthostatic hypotension was found in 8 patients (12.6%) and 4 children (6.2%) in the control group. When compared to the control group, patients with MVP had higher QTc dispersion, frontal QRS-T angle, Tp-e interval, and Tp-e/QTc ratio. There was no significant difference between the two groups in terms of conventional measurements of heart rate variability in the Holter ECG, as well as no significant difference in HRDC.
 Conclusion: Although cases with pathological findings in the initial ECG were excluded from our study, we believe that the high frontal QRS-T angle observed in MVP patients is a novel and significant finding. Furthermore, it has been discovered that HRDC, a new and understudied parameter in children, does not show a significant difference in patients with MVP.

High-risk phenotypes of arrhythmic mitral valve prolapse: a systematic review and meta-analysis

Background Mitral valve prolapse (MVP) is associated with aggravated risk of ventricular tachycardia (VT), ventricular fibrillation (VF) and sudden cardiac death (SCD). There is a lack of specific guideline recommendation regarding risk stratification and management, despite multiple proposed high-risk phenotypes. We performed systematic review and meta-analysis to evaluate high-risk phenotypes for malignant arrhythmias in patients with MVP. Methods We comprehensively searched the databases of MEDLINE, SCOPUS, and EMBASE from inception to April 2023. Included studies were cohort and case-control comparing between MVP patients with and without VT, VF, cardiac arrest, ICD placement, or SCD. Data from each study were combined using the random-effects. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results Nine studies from 1985 to 2023 were included involving 2,279 patients with MVP. We found that T-wave inversion (OR 2.52; 95% CI: 1.90–3.33; p < 0.001), bileaflet involvement (OR 2.28; 95% CI: 1.69–3.09; p < 0.001), late gadolinium enhancement (OR 17.05; 95% CI: 3.41–85.22; p < 0.001), mitral annular disjunction (OR 3.71; 95% CI: 1.63–8.41; p < 0.002), and history of syncope (OR 6.96; 95% CI: 1.05–46.01; p = 0.044), but not female (OR 0.96; 95% CI: 0.46–2.01; p = 0.911), redundant leaflets (OR 4.30; 95% CI: 0.81–22.84; p = 0.087), or moderate-to-severe mitral regurgitation (OR 1.24; 95% CI: 0.65–2.37; p = 0.505), were associated with those events. Conclusion Bileaflet prolapse, T-wave inversion, mitral annular disjunction, late gadolinium enhancement, and history of syncope are high-risk phenotypes among population with MVP. Further research is needed to validate the risk stratification model and justify the role of primary prophylaxis against malignant arrhythmias.

Predictors of Ventricular Arrhythmias in Patients With Mitral Valve Prolapse: A Meta-analysis.

Mitral valve prolapse (MVP) has an estimated prevalence of 2-3% in the general population. Patients with MVP have an increased risk of ventricular arrhythmic events. The aim of this meta-analysis was to identify easily obtained markers that can be used for the arrhythmic risk stratification of MVP patients. This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement). The search strategy identified 23 studies that were finally included in the study. The quantitative synthesis showed that late gadolinium enhancement (LGE) [RR 6.40 (2.11-19.39), I2 77%, P = 0.001], longer QTc interval [mean difference: 14.2 (8.92-19.49) I2 0%, P < 0.001], T-wave inversion in inferior leads [RR 1.60 (1.39-1.86), I2 0%, P < 0.001], mitral annular disjunction (MAD) [RR 1.77 (1.29-2.44), I2 37%, P = 0.0005], lower left ventricular ejection fraction (LVEF) [mean difference: -0.77 (-1.48, -0.07) I2 0%, P = 0.03], bileaflet MVP [RR 1.32 (1.16-1.49), I2 0%, P < 0.001], increased anterior [mean difference: 0.45 (0.28, 0.61), I2 0%, P < 0.001] and posterior [mean difference: 0.39 (0.26, 0.52), I2 0%, P < 0.001] mitral leaflet thickness were significantly associated with ventricular arrhythmias in MVP patients. On the other hand, gender, QRS duration, anterior, and posterior mitral leaflet length were not associated with increased risk of arrhythmias. In conclusion, inferior T-wave inversions, QTc interval, LGE, LVEF, MAD, bileaflet MVP, anterior, and posterior mitral leaflet thickness are easily obtained markers that can be used for the risk stratification of patients with MVP. Prospective studies should be designed for the better stratification of this population.

Difference in left ventricular reverse remodelling after mitral valve surgery between mitral valve prolapse subtypes: barlows disease versus fibroelastic deficiency

Abstract Funding Acknowledgements Type of funding sources: None. Background Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodelling in patients with mitral valve prolapse (MVP), however it is currently unknown whether this process is similar in Barlow’s Disease (BD) and Fibroelastic Deficiency (FED). Particularly the recently suggested concomitant cardiomyopathy in BD could affect LV (reverse) remodelling beyond volume overload. Purpose Evaluate LV reverse remodelling after mitral valve surgery in patients with BD versus FED. Methods Retrospective analysis of all MVP patients with severe MR who underwent mitral valve surgery at a single tertiary center. We assessed MR severity, LV volumes and systolic/diastolic function by transthoracic echocardiography before surgery and 6 months post-operative. Results A total of 55 MVP patients with BD (n=24) or FED (n=31) were enrolled between January 2013 and July 2022. Both BD and FED showed a male predominance (58.3% and 80.6% respectively, p = 0.071) and patients with BD were generally younger (52 ± 13 vs. 63 ± 12 years old; p = 0.005). Baseline LV end-diastolic (LVEDV), end-systolic volumes (LVESV) and LVEF were similar between BD and FED. In addition, pre-operative MR severity (evaluated by a multi-integrative approach) was not significantly different between both groups. However, patients with BD presented with a larger prolapse volume (12.2 ± 8.2 ml versus 5.8 ± 4.7 ml; p = 0.004) and larger mitral annulus diameter (37 ± 6 mm versus 33 ± 5 mm; p = 0.016) compared to FED. Overall, mitral valve repair with annuloplasty, neochord and/or triangular/quadrangular resection were the most frequent surgical interventions. Mitral valve replacement was performed in selected patients when valve repair was not feasible, mainly in BD (45.8% vs. 19.4%; p = 0.035). After a median follow-up period of 281 days, residual MR (≥grade 2) was present in 16.1% of patients with FED versus 8.3% with BD (p = 0.390). LV reverse remodelling was present in both groups, with a similar decrease in LVEDV (19.2 ± 18.8 ml/m2 in BD versus 24.4 ± 20.0 ml/m2 in FED; p = 0.337). Interestingly, the less load-dependent LVESV showed a trend towards less reverse remodelling in BD (3.4 ± 11.0 ml/m2 versus 7.5 ± 9.0 ml/m2; p = 0.138), which resulted in a significantly lower LVEF in BD versus FED (51.7 ± 7.6% versus 56.3 ± 6.1%; p = 0.016). Of note, LVEF at follow-up was independent of sex, comorbidities, baseline LV volumes and type of surgical intervention. Conclusions While patients with BD and FED showed similar MR severity, LV volumes and LVEF at baseline, post-operative LVEF was significantly lower in patients with BD. These findings suggest that LV (reverse) remodelling in BD could be affected by other mechanisms beyond volume overload, like a concomitant cardiomyopathy.

Segmental longitudinal strain and regional myocardial work index could help identify mitral valve prolapse patients with increased risk of ventricular arrhythmia

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Mitral valve prolapse (MVP) could associate with malignant ventricular arrhythmias. Mitral annular disjunction (MAD), which leads to excessive mobility, mechanical stretch, and myocardial damage, has been studied as a putative mechanism for an arrhythmic substrate. However, it is unclear whether that is the only sufficient arrhythmic risk factor in that patients. The aim of our study was to check whether two–dimensional speckle tracking echocardiography (STE) with segmental longitudinal strain and STE-derived myocardial work (MW) analysis may allow for a more accurate assessment of the arrhythmic risk in MVP patients. Methods and results Seventy-two MVP patients and twenty healthy volunteers enrolled in the study had performed echocardiography with STE assessment. Non-sustained ventricular tachycardia (NSVT) was the arrhythmic outcome for further calculations. Pre-specified cut-off values for peak segmental longitudinal strain (PSS) and segmental myocardial work index (MWI) for basal lateral (−25% and 2200 mmHg%), mid-lateral (−25% and 2500 mmHg%), mid posterior (−25% and 2400 mmHg%), and mid inferior (−23% and 2400 mmHg%) segments were accurate predictors of NSVT. A combination of PSS and MWI increased the probability of NSVT occurrence, reaching the highest predictive value for the basal lateral segment (Figure): odds ratio 32.15 (3.78–273.8), p &amp;lt; 0.001 for PSS ≥ (−25%) and MWI ≥ 2200 mmHg%. Conclusions 2D STE may be a valuable tool for assessing arrhythmic risk in MVP patients. Excessively increased segmental longitudinal strain with augmented regional myocardial work index identifies patients with the highest risk of NSVT.

Mitral Valve Prolapse and Sudden Cardiac Death in Athletes at High Risk.

Mitral valve prolapse (MVP) is the most frequent valvulopathy in the general population, with usually a favourable prognosis. Although it can be associated with some complications, ventricular arrhythmias (VA) and sudden cardiac death (SCD) are the most worrying. The estimated risk of SCD in MVP is between 0.2% to 1.9% per year, including MVP patients with and without severe mitral regurgitation (MR). The association between SCD and MVP is expressed by a phenotype called "malignant MVP" characterized by transthoracic echocardiography (TTE) findings such as bileaflet myxomatous prolapse and mitral annulus disjunction (MAD), ECG findings such as repolarization abnormalities, complex ventricular arrhythmias (c-VAs) and LV fibrosis of papillary muscles (PMs) and inferobasal wall visualized by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Therefore, attention is raised for patients with "arrhythmic MVP" characterized from an ECG point of view by frequent premature ventricular contractions (PVCs) arising from one or both PMs as well as by T-wave inversion in the inferolateral leads. In athletes, SCD is the most frequent medical cause of death and in young subjects (< 35 years) usually is due to electrical mechanism affecting who has a silent cardiovascular disease and are not considered per se a cause of increased mortality. In MVP, SCD was reported to happen during sports activity or immediately after and valve prolapse was the only pathological aspect detected. The aim of the present paper is to explore the association between SCD and MVP in athletes, focusing attention on ECG, TTE in particular, and CMR findings that could help to identify subjects at high risk for complex arrhythmias and eventually SCD. In addition, it is also examined if sports activity might predispose patients with MVP to develop major arrhythmias.

Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse.

We investigated the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of mitral valve prolapse (MVP). For RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from five patients with MVP, with or without chordae tendineae rupture, and five healthy individuals. High-throughput sequencing was used for RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) analysis, alternative splicing (AS) analysis, functional enrichment analysis, co-expression of RBPs, and alternative splicing events (ASEs) analysis were conducted. The MVP patients exhibited 306 up-regulated genes and 198 down-regulated genes. All down- and up-regulated genes were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested. We identified 13 RNA-binding proteins (RBPs) from the DEGs and screened out four RBPs (ZFP36, HSPA1A, TRIM21, and P2RX7). We selected four RASEs based on the co-expression analyses of RBPs and RASEs, including exon skipping (ES) of DEDD2, alternative 3' splice site (A3SS) of ETV6, mutually exclusive 3'UTRs (3pMXE) of TNFAIP8L2, and A3SS of HLA-B. Furthermore, the selected four RBPs and four RASEs were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and showed high consistency with RNA sequencing (RNA-seq). Dysregulated RBPs and their associated RASEs may play regulatory roles in MVP development and may therefore be used as therapeutic targets in the future.

Left Ventricle Segmental Longitudinal Strain and Regional Myocardial Work Index Could Help Determine Mitral Valve Prolapse Patients with Increased Risk of Ventricular Arrhythmias

Mitral valve prolapse (MVP) could associate with malignant ventricular arrhythmias (VAs). Mitral annular disjunction, a putative mechanism for an arrhythmic substrate, leads to excessive mobility, stretch, and damage of some segments. Speckle tracking echocardiography (STE), with particular attention to the segmental longitudinal strain and myocardial work index (MWI), could be an indicator of the segments we aimed to check. Seventy-two MVP patients and twenty controls underwent echocardiography. Complex VAs documented prospectively after the enrollment was qualified as the primary endpoint, which was noticed in 29 (40%) patients. Pre-specified cut-off values for peak segmental longitudinal strain (PSS) and segmental MWI for basal lateral (-25%, 2200 mmHg%), mid-lateral (-25%, 2500 mmHg%), mid-posterior (-25%, 2400 mmHg%), and mid-inferior (-23%, 2400 mmHg%) segments were accurate predictors of complex VAs. A combination of PSS and MWI increased the probability of the endpoint, reaching the highest predictive value for the basal lateral segment: odds ratio 32.15 (3.78-273.8), p < 0.001 for PSS ≥ -25% and MWI ≥ 2200 mmHg%. STE may be a valuable tool for assessing the arrhythmic risk in MVP patients. Excessively increased segmental longitudinal strain with an augmented regional myocardial work index identifies patients with the highest risk of complex VAs.

Histopathological insights into mitral valve prolapse-induced fibrosis.

Mitral valve prolapse (MVP) is a cardiac valve disease that not only affects the mitral valve (MV), provoking mitral regurgitation, but also leads to maladaptive structural changes in the heart. Such structural changes include the formation of left ventricular (LV) regionalized fibrosis, especially affecting the papillary muscles and inferobasal LV wall. The occurrence of regional fibrosis in MVP patients is hypothesized to be a consequence of increased mechanical stress on the papillary muscles and surrounding myocardium during systole and altered mitral annular motion. These mechanisms appear to induce fibrosis in valve-linked regions, independent of volume-overload remodeling effects of mitral regurgitation. In clinical practice, quantification of myocardial fibrosis is performed with cardiovascular magnetic resonance (CMR) imaging, even though CMR has sensitivity limitations in detecting myocardial fibrosis, especially in detecting interstitial fibrosis. Regional LV fibrosis is clinically relevant because even in the absence of mitral regurgitation, it has been associated with ventricular arrhythmias and sudden cardiac death in MVP patients. Myocardial fibrosis may also be associated with LV dysfunction following MV surgery. The current article provides an overview of current histopathological studies investigating LV fibrosis and remodeling in MVP patients. In addition, we elucidate the ability of histopathological studies to quantify fibrotic remodeling in MVP and gain deeper understanding of the pathophysiological processes. Furthermore, molecular changes such as alterations in collagen expression in MVP patients are reviewed.

363 TRICUSPID ANNULUS DISJUNCTION: THE MISSING PIECE IN THE ARRHYTHMIC MITRAL VALVE PROLAPSE?

Abstract Background Arrhythmic mitral valve prolapse (MVP) is characterized by left ventricular (LV) fibrosis, due to an excessive myocardial stretch on the LV basal-mid inferolateral wall. Mitral annulus disjunction (MAD) and curling are common findings in arrhythmic MVP patients, thus representing the excessive traction of mitral apparatus on myocardium. Cardiac magnetic resonance (CMR) demonstrated to clearly identify these typical morpho-functional alterations, as well as LV fibrosis, in MVP patients. The involvement of right-sided annulus disease recently emerged as an interesting missing piece in the natural history of MVP patients. However, its role in a population of arrhythmic MVP patients in absence of significant mitral regurgitation (MR) has not been evaluated. Purpose The primary aim of the study was to evaluate the prevalence and the role of tricuspid annulus disjunction (TAD) in the arrhythmic MVP patients. Secondly, we evaluated the role of TAD in the prevalence and severity of the common morpho-functional alterations of MVP, MAD and curling. Methods Consecutive MVP patients with normal systolic function and without significant MR, referred for palpitations, were enrolled. Morpho-biventricular evaluations, including MAD and curling assessment, as well as LV fibrosis were evaluated using CMR. Results 66 patients met the inclusion criteria (29% male, median age 44 years). TAD was identified in 22 MVP patients (27% male, median age 52 years). No differences for ventricular arrhythmias (p: 0.459) between MVP patients without (n: 44) and with TAD (n: 22) were identified. MVP patients with TAD were older (52 vs 42 years, p: 0.009) and presented reduced biventricular end-diastolic volumes, despite normal, in comparison with those without TAD (left ventricle: 80.5 vs 93.5 ml/m2, p: 0.002; right ventricle: 72.5 vs 85.5 ml/m2, p: 0.018). MAD and curling were more common in patients without TAD (respectively, 25 vs 19, p:0.014 and 24 vs 20, p: 0.002) than in those with TAD. Conversely, MAD and curling are more severe in patients with TAD (respectively, 5.9 vs 4.7 mm and 4 vs 3 mm, both p: 0.034) than in those without TAD. No differences for LGE distribution were identified in the two groups (p: 0.062). Conclusion In arrhythmic MVP patients, presence of TAD was associated with a great severity of MAD and curling. So, despite uncommon, the contextual presence of TAD and MAD in arrhythmic MVP patients suggests a more severe biannular disease, characterized by an increased biventricular myocardial stretch. Conversely to MAD, TAD wasn't associated with ventricular arrhythmias. Thus, its role in ventricular arrhythmogenesis in MVP patients appeared limited.

Abstract 12600: Mitral Annular Disjunction: How Accurate Are We? A Cardiovascular MRI Study Defining Risk

Background: Mitral Annular Disjunction (MAD) refers to embryologic fibrous separation between mitral annular ring and basal left ventricular myocardium. Since its original description, the role of MAD in arrhythmic mitral valve prolapse (MVP) has been subject of active research. In this study we sought to assess prognostic and imaging characteristics of MVP patients with and without underlying MAD. Methods: Patients with posterior or bi-leaflet MVP were retrospectively identified via a review of all patients referred to our cardiac magnetic resonance (CMR) imaging laboratory from January 2015 to May 2022. MVP patients were further stratified by underlying MAD status. CMR characteristics including late gadolinium enhancement (LGE) distribution, clinical characteristics, and data on mitral valve intervention were determined. Results: A total of 100 MVP patients undergoing CMR imaging (52 MVP patients with posterior MAD) were retrospectively identified with female comprising 55% of the cohort. MVP patients with MAD were more likely to have an abnormal basal inferolateral/ papillary muscles LGE (51% vs 21%, p&lt;0.01). Posterior MAD longitudinal disjunction gap in ‘mm’ was a predictor of ventricular tachycardia (VT) [1.23, p=0.03)]. Similarly, posterior MAD as a binary variable was predictor of VT (11, p&lt;0.01), ventricular arrhythmia (composite of VT, and non-sustained VT) (2.4, p=0.03), and major adverse cardiac events (MACE) (composite of VT, syncope, and mitral valve intervention) (2.5, p=0.03). Using ROC curve analysis, a disjunction gap of &gt; 4 mm was predictive of VT (AUC-0.71, p&lt;0.01), and incorporation of LGE in ROC model further improved AUC to 0.78 confirmed via Akaike information criterion (p&lt;0.05), see Figure. Conclusion: Abnormal LGE involving basal inferolateral myocardium and papillary muscles may provide substrate for arrythmia in MVP patients. Further, for the first time, a MAD threshold of &gt; 4 mm is demonstrated to stratify the VT risk.

Abstract 15014: Aberrant, Elevated Papillary Muscle and Left Ventricular Wall Forces Associated With Mitral Valve Prolapse Are Normalized by Surgical Neochordal Repair but Not by Transcatheter Edge-to-Edge Repair

Introduction: Recent studies have linked mitral valve prolapse (MVP) to localized myocardial fibrosis and ventricular arrhythmia, and early imaging work has shown altered ventricular motion with papillary muscle (PM) traction in MVP and MitraClip patients. We aimed to biomechanically compare MitraClip and neochordal repair for MVP on PM forces ex vivo . Methods: We developed a force transduction system to measure the forces exerted on the PMs throughout the cardiac cycle in a left heart simulator ( Fig A ) with consistent pressures. Using a randomized, paired procedure with porcine MVs (n=4), we measured the hemodynamics and forces for control, diseased (P2 prolapse via chordal rupture), MitraClip repair ( Fig B, C, D ) (single P2 clip), and neochordal repair (P2 primary neochord on each PM) conditions. Results: We found that MitraClip PM forces (7.19 ± 0.31 N) are higher by 9.34% compared with those of controls (6.58 ± 0.21 N, p&lt;0.001 ). This result is similar to MVP valves modeled by superior PM displacement, which showed 9.23% higher forces than those of controls (n=10, p&lt;0.001 ). Moreover, MitraClip repaired valves showed PM force increases of 6.4% compared with forces of neochordal repair (6.76 ± 0.22 N, p&lt;0.001 ), despite having similarly reduced regurgitation fractions (5.05% ± 1.98% vs. 4.25% ± 1.51%, respectively, p&gt;0.05 ) compared with those of the diseased state (16.96% ± 3.04%, p&lt;0.001 ) and controls (2.66% ± 0.87%). Additionally, neochordal repair valves had 2.79% higher forces compared to those of control valves ( p&lt;0.001 ). Conclusions: We discovered that MitraClip, while reducing regurgitation, does not restore aberrant forces on the PM induced in MVP to baseline or reduced levels, while neochordal repair does. Our work suggests that these elevated forces, associated with MVP and MitraClip, predisposes the MV to continued traction, which may present a long-term harm to patients by catalyzing localized fibrosis and ventricular arrhythmia.

Real-time ultrasound elastographic features and color doppler imaging of mitral valve prolapse

Background: The aim of this study was to investigate the elasticity of ocular structures in patients with mitral valve prolapse (MVP).&#x0D; Material and Methods: This prospective study included a total of 35 patients with MVP (study group) and 35 healthy volunteers (control group). The elastography value of the ratio of orbital fat- sclera (ROF/S) was measured with real-time US elastography. For each eye, central retinal artery (CRA), posterior ciliary artery (PCA), and ophthalmic artery (OA) were evaluated, respectively. &#x0D; Results: The mean ages of the patients in the study and the control groups were 31.77 ± 11.40 years, and 30.65 ± 7.45 years, respectively (P =0.511). Mean ROF/S were 1.95 ± 0.81 and 1.37 ± 1.06 (P=0.001) in the study groups and control, respectively. The mean RI of the OA was 0.67 ± 0.05 in the control group, 0.67 ±0.05 (0.55; 0.87) in study group. The mean RI of the PCA was 0.66 ± 0.05 in the control group, 0.68 ±0.06 in study group. . The mean RI of the CRA was 0.66 ± 0.05 in the control group, 0.66 ±0.06 in study group. The RI value was not a significant difference between control and study group (p &gt; 0.05).&#x0D; Conclusion: Scleral elasticity was significantly increased in MVP patients. These could be related to ocular pathologies such as glacouma, kerataconus in MVP.

Quantification of left ventricular fibrosis in arrhythmic mitral valve prolapse patients: comparison of different semi-automated techniques assessed by cardiac magnetic resonance

Abstract Background Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in mitral valve prolapse (MVP) patients. Cardiac magnetic resonance (CMR) demonstrated able to clearly identify LV fibrosis with the post-contrast late gadolinium enhancement (LGE) images. Despite the pivotal role of LV fibrosis in the arrhythmogenesis, a quantification and identification of reproducible method able to accurately measure LGE in arrhythmic MVP patients has not been recognized. Purpose We aimed to measure and compare different semi-quantitative methods for LGE quantification assessed by CMR, in order to identify the most reproducible one, in arrhythmic MVP patients. Methods 66 arrhythmic MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding technique using full with at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with visual assessment (Fig. 1). Results LGE was identified in 41 arrhythmic MVP patients (62%) and quantified (Fig. 2). The mean quantity of LGE visually assessed was 2.40±1.07% or 1.40±0.82 g. With FWHM, LGE resulted 3.56±1.23% or 1.99±1.13 g. Using thresholding, the mean LGE quantity was 9.2±3.1% or 4.82±2.28 g for 2-SD, 5.72±1.75% or 3.06±1.47 g for 3-SD and 2.36±0.99% or 1.29±0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.402±1.075 vs 2.363±0.9909, p: 0.543). Despite all semi-quantitative methods for LGE quantification demonstrated a good intra and inter-observer agreement, the 5-SD threshold quantification, both in percentage and in grams, revealed the less intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935) when compared with visual assessment. Conclusion This is the first study that quantified and compared different CMR semi-automated methods for LGE assessment in a population of arrhythmic MVP patients. The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility. Funding Acknowledgement Type of funding sources: None.

Mitral valve prolapse: From new mechanisms to diagnostic challenges.

Mitral valve prolapse (MVP) is the most common primary valvular abnormality, associated with various degrees of incompetent function and sequelae, including heart failure and sudden cardiac death. Recent improvements in echocardiographic techniques and new insights into mitral valve anatomy and physiology have rendered the diagnosis of this condition more accurate and reliable. Here we review the genetic etiology, clinical significance, diagnosis, and treatment options for MVP patients.