The Association Between Late Gadolinium Enhancement by Cardiac Magnetic Resonance and Ventricular Arrhythmia in Patients With Mitral Valve Prolapse: A Systematic Review and Meta-Analysis.

INTRODUCTION: Malignant ventricular arrhythmia (VA) and sudden cardiac death (SCD) have been reported in patients with mitral valve prolapse (MVP); however, effective risk stratification methods are still lacking. Myocardial fibrosis is thought to play an important role in the development of VA; however, observational studies have produced contradictory findings regarding the relationship between VA and late gadolinium enhancement (LGE) in MVP patients. The aim of this meta-analysis and systematic review of observational studies was to investigate the association between left ventricular LGE and VA in patients with MVP. METHODS: We searched the PubMed, Embase, and Web of Science databases from 1993 to 2023 to identify case-control, cross-sectional, and cohort studies that compared the incidence of VA in patients with MVP who had left ventricular LGE and those without left ventricular LGE. RESULTS: A total of 1464 subjects with MVP from 12 observational studies met the eligibility criteria. Among them, VA episodes were reported in 221 individuals (15.1%). Meta-analysis demonstrated that the presence of left ventricular LGE was significantly associated with an increased risk of VA (pooled risk ratio 2.96, 95% CI: 2.26-3.88, p for heterogeneity = 0.07, I2 = 40%). However, a meta-regression analysis of the prevalence of mitral regurgitation (MR) showed that the severity of MR did not significantly affect the association between the occurrence of LGE and VA (p = 0.079). CONCLUSION: The detection of LGE could be helpful for stratifying the risk of VA in patients with MVP.

Primary Atriopathy in Mitral Valve Prolapse: Echocardiographic Evidence and Clinical Implications.

BACKGROUND: Prominent multi-scallop systolic leaflet displacement toward the left atrium (atrialization) is typically observed in bileaflet mitral valve prolapse (MVP) with mitral annular disjunction. We hypothesized that mitral leaflet atrialization is associated with an underlying left atrial (LA) myopathy characterized by progressive structural and functional abnormalities, irrespective of mitral regurgitation (MR) severity. METHODS: We identified 334 consecutive patients with MVP, no prior atrial fibrillation, and comprehensive clinical and echocardiographic data. LA function was assessed by LA reservoir strain, LA function index, and LA emptying fraction. We also classified the stage of LA remodeling based on LA enlargement and LA reservoir strain (stage 1: no remodeling; stage 2: mild remodeling; stage 3: moderate remodeling; and stage 4: severe remodeling). The primary end point was the composite risk of sudden arrhythmic death, heart failure hospitalization, or the new onset of atrial fibrillation. RESULTS: Bileaflet MVP with no or mild MR had a lower LA reservoir strain (P=0.04) and LA function index (P<0.001) compared with other MVP subtypes. In multivariable linear regression adjusted for cardiovascular risk factors and MR ≥moderate, bileaflet MVP remained significantly associated with lower LA function parameters (all P<0.05). There was a significant increase in the risk of events as the LA reservoir strain and LA remodeling stage increased (P<0.001). In multivariable analysis, stage 4 of LA remodeling remained significantly associated with a higher risk of events compared with stage 1 (hazard ratio, 6.09 [95% CI, 1.69-21.9]; P=0.006). CONCLUSIONS: In a large MVP registry, bileaflet involvement is associated with reduced LA function regardless of MR severity, suggesting a primary atriopathy in this MVP subtype. Abnormal LA function, particularly when assessed through a multiparametric approach, is linked to a higher risk of cardiovascular events and may improve risk stratification in MVP, even in those without significant MR.

Mitral valve prolapse: arrhythmic risk during pregnancy and postpartum.

BACKGROUND AND AIMS: Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. METHODS: This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. RESULTS: The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). CONCLUSIONS: The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Infant Barlow's Disease in Association with Atrial Septal Defect.

CLINICAL DATA: Female, seven years old, referred to our service complaining about congestive heart failure symptoms due to mitral valve regurgitation and atrial septal defect. Technical description: Echocardiographic findings compatible with Barlow's disease and atrial septal defect, ostium secundum type. OPERATION: She was submitted to mitral valvuloplasty with chordal shortening and prosthetic posterior ring (Gregori-Braile®) along with patch atrioseptoplasty. COMMENTS: Mitral valve regurgitation is a rare congenital heart disease and Barlow's disease is probably rarer. Mitral valve repair is the treatment of choice.

Evaluation of left ventricular function in patients with mitral annular disjunction using speckle tracking echocardiography.

BACKGROUND: Mitral annular disjunction (MAD) is a structural abnormality characterized by the systolic detachment of the posterior mitral annulus and the ventricular myocardium. It is usually observed coexistent with mitral valve prolapse (MVP) and associated with a mechanical dysfunction despite preserved electrical isolation function of the mitral annulus. This study aimed to evaluate left ventricular (LV) function using speckle tracking echocardiography in MVP patients with MAD. METHODS: This study was designed as a prospective, single-center study including 103 patients with MVP and 40 age- and sex-matched control subjects. Transthoracic echocardiography and cardiac magnetic resonance imaging were performed to assess LV function and MAD presence. RESULTS: MAD (+) MVP (n = 34), MAD (-) MVP (n = 69), and control (n = 40) groups were enrolled in the study. Among the MVP patients, 34 (33%) had MAD. T-negativity in the inferior leads on electrocardiography was more frequent in the MAD (+) group than in the MAD (-) patients (4.3% vs. 20.6%, p = .014). Mitral regurgitation degree, Pickelhaube sign (17.6% vs. 1.4%, p = .005), and late gadolinium enhancement frequency (35.3% vs. 10.6%, p = .002) were significantly higher in MAD (+) patients. MAD (+) patients had significantly impaired global longitudinal strain (-23.1 ±  2.1 vs. -23.5 ± 2.3, p < .001), basal longitudinal strain (BLS) (-19.6 ±  1.5 vs. -20.5 ± 1.9, p < .001), Mid-Ventricular Longitudinal Strain (-22.2 ± 1.7 vs. -23.2 ± 2.2, p < .001) and LA strain (-24.5 ± 3.9 vs. -27.2 ± 3.6, p < .001) when compared to MAD (-) MVP patients, despite similar LV ejection fraction. All these values of MVP patients were also significantly lower than the control group. The mean MAD distance was 7.8 ± 3.2 mm in MAD (+) patients. Patients with two or more symptoms were higher in the MAD (+) group than in the MAD (-) group (4.3% vs. 44.1%, p < .001). CONCLUSION: This study demonstrated a significant decrease in longitudinal strain in MVP patients with MAD, indicating myocardial dysfunction. These findings suggest that MAD may contribute to LV dysfunction and highlight the importance of early detection in younger patients. Further research is needed to explore the functional implications and long-term outcomes of MAD.

Mitral annular disjunction and mitral valve prolapse extrapolating adult data to an adolescent cohort?

PURPOSE OF REVIEW: The aim of this study is to provide an update on mitral valve prolapse (MVP) and mitral annular disjunction (MAD) and who may be at risk for ventricular arrhythmias and sudden cardiac death. RECENT FINDINGS: MVP is generally considered a benign condition. However, a small subset of patients may be at risk for life-threatening ventricular arrhythmias. Among the risk factors identified in adults include patients with bileaflet mitral valves, myxomatous changes, myocardial fibrosis, and the presence of MAD. Advances in multimodal imaging have allowed for improved identification of fibrosis, anatomical valve derangements, and the amount of MAD. Recent guidelines have suggested that patients with MVP with or without MAD may be at risk for life-threatening arrhythmias if they have had prior ventricular arrhythmias, ventricular dysfunction, or unexplained syncope. Yet, extrapolation of adult data to a pediatric cohort with similar MVP and MAD at this juncture is challenging. There is, however, early evidence that some pediatric patients with significant myocardial fibrosis or abnormal tissue Doppler may be at risk for ventricular tachycardia. SUMMARY: Mitral valve prolapse and mitral annular disjunction at times coexist and at other times can be seen as isolated entities. While the incidence of arrhythmic MVP is quite rare, there is increasing evidence that certain select adults with MVP may be at risk for ventricular tachycardia and sudden cardiac death. Future multicenter studies are needed to better understand the natural history of arrhythmic mitral valve disease and how early disease manifestation in children may impact findings now being reported in young adults.

What Do We Know So Far About Ventricular Arrhythmias and Sudden Cardiac Death Prediction in the Mitral Valve Prolapse Population? Could Biomarkers Help Us Predict Their Occurrence?

PURPOSE OF THE REVIEW: To summarize currently available data on the topic of mitral valve prolapse (MVP) and its correlation to the occurrence of atrial and ventricular arrhythmias. To assess the prognostic value of several diagnostic methods such as transthoracic echocardiography, transesophageal echocardiography, cardiac magnetic resonance, cardiac computed tomography, electrocardiography, and electrophysiology concerning arrhythmic episodes. To explore intra and extracellular biochemistry of the cardiovascular system and its biomarkers as diagnostic tools to predict rhythm disturbances in the MVP population. RECENT FINDINGS: MVP is a common and mainly benign valvular disorder. It affects 2-3% of the general population. MVP is a heterogeneous and highly variable phenomenon with three structural phenotypes: myxomatous degeneration, fibroelastic deficiency, and forme fruste. Exercise intolerance, supraventricular tachycardia, and chest discomfort are the symptoms that are often paired with psychosomatic components. Though MVP is thought to be benign, the association between isolated MVP without mitral regurgitation (MR) or left ventricle dysfunction, with ventricular arrhythmia (VA) and sudden cardiac death (SCD) has been observed. The incidence of SCD in the MVP population is around 0.6% per year, which is 6 times higher than the occurrence of SCD in the general population. Often asymptomatic MVP population poses a challenge to screen for VA and prevent SCD. Therefore, it is crucial to carefully assess the risk of VA and SCD in patients with MVP with the use of various tools such as diagnostic imaging and biochemical and genetic screening.

Quantification of Mitral Regurgitation in Mitral Valve Prolapse by Three-Dimensional Vena Contracta Area: Derived Cutoff Values and Comparison With Two-Dimensional Multiparametric Approach.

BACKGROUND: Echocardiographic grading of mitral regurgitation (MR) in mitral valve prolapse (MVP) is challenging. Three-dimensional (3D) vena contracta area (VCA) has been proposed as a valuable method. However, data defining the cutoff values of severity and validation in the subset of patients with MVP are scarce. The aim of this study was to validate the 3D VCA by 3D color-Doppler transesophageal echocardiography (TEE) in patients with MVP and to define the cutoff values of severity grading. The secondary aim was to compare 3D VCA to the effective regurgitant orifice area estimation by proximal isovelocity surface area (EROA-PISA) method. METHODS: A total of 1,138 patients with at least moderate MR who underwent TEE were included. Three-dimensional VCA was measured, and the cutoff value and area under the curve (AUC) for the prediction of severe MR were estimated by receiver operating characteristic curve using a guideline-suggested multiparametric approach as the reference standard. In a subgroup of patients, 3D regurgitant volume (RV) and 3D fraction were calculated from mitral and left ventricular outflow tract stroke volumes to further validate 3D VCA against a 3D volumetric reference standard. RESULTS: The optimal 3D VCA cutoff value for predicting severe MR was 0.45 cm2 (specificity, 0.87; sensitivity, 0.90) with an AUC of 0.95 using a multiparametric approach as reference. Three-dimensional VCA had a good linear correlation with EROA-PISA (r = 0.62, P < .05) with larger values compared to EROA-PISA (0.63 cm2 vs 0.44 cm2, P < .05). A cutoff of 0.50 cm2 (AUC of 0.84; sensitivity, 0.78; specificity, 0.78) predicts an EROA-PISA of 0.40 cm2. Three-dimensional VCA had a good linear correlation with 3D RV (r = 0.56, P < .01), with an AUC of 0.86 to predict a 3D fraction >50%. CONCLUSIONS: The present study suggests 0.45 cm2 as the best cutoff value of 3D VCA to define severe MR in patients with MVP, showing an optimal agreement with the reference standard multiparametric approach and 3D RV.

Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis. OBJECTIVES: This study investigated the determinants of VA in patients with MVP without significant regurgitation. METHODS: This study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern. RESULTS: The 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA. CONCLUSIONS: In patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA.

Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.

Insights into malignant mitral valve degenerative disease from a sudden cardiac death cohort highlighting significant measurement differences from normal.

AIMS: Mitral valve prolapse (MVP) is an accepted cause of sudden cardiac death (SCD) in most autopsy series. Diagnosis at autopsy relies upon subjective assessment with no established objective pathological criteria. This study set out to establish objective measurements to help pathologists dealing with SCD. METHODS: We diagnosed 120 (1.5%) cases of MVP in 8108 cases of SCD. We measured the mitral annulus, anterior and posterior leaflets, rough zone and mitral annular disjunction (MAD) in 27 MVP cases and compared them to 54 age- and sex-matched normal mitral valves. RESULTS: Age of death was 39 ± 16 years, with 59 females and 61 males. History of mild MV disease was present in 19 (16%). Eleven (9%) died associated with exertion. Left ventricular hypertrophy was present in nine (15%) females and 10 (16%) males. Both MV leaflets showed thickening and ballooning in all individuals. MVP showed highly significantly increased annular circumference, elongation and thickening of both leaflets as well as increased MAD (all P < 0.001). Left ventricular fibrosis was present in 108 (90%), with interstitial fibrosis in the posterolateral wall and papillary muscle in 88 (81%) and coexisting replacement fibrosis in 40 (37%). CONCLUSION: This is the largest MVP associated with SCD series highlighting a young cohort with equal representation of males and females. There is involvement of both leaflets with significant annular dilatation, elongation and thickening of both leaflets with MAD. Left ventricular fibrosis explains arrhythmia. Our quantitative measurements should serve as a reference for pathologists assessing post-mortem hearts for MVP.

Feasibility of concomitant exclusion of left atrial appendage during novel transapical off-pump beating heart mitral valve repair.

The AtriClip device enables the safe and reproducible epicardial clipping of the left atrial appendage. Transapical off-pump beating heart mitral valve repair using NeoChord DS100 Artificial Chordae Delivery System has matured and become more standardized. We aim to evaluate the feasibility of combining NeoChord repair and left atrial appendage exclusion in a single procedure through the same minithoracotomy in patients with mitral valve prolapse and atrial fibrillation. From 2018 to 2019, seven patients with severe mitral regurgitation and atrial fibrillation underwent transesophageal echocardiography-guided transapical off-pump mitral valve repair with the novel NeoChord DS 1000 system and concomitant left atrial appendage exclusion using the AtriClip Pro II device. Both procedures were performed via left mini-thoracotomy. The AtriClip device was applied after the NeoChord repair was done. All seven patients had less than moderate mitral regurgitation after the NeoChord repair and successful left atrial appendage occlusion. There were no device or procedure-related complications. Clinical follow-up revealed significant symptomatic improvement, and no cardiovascular complications were reported. Transesophageal echocardiography at 6-12 months post-procedure showed stable left atrial appendage occlusion with no residual flow between the left atrium and the left atrial appendage and a stump of less than 5 mm. Beating heart epicardial clipping of the left atrial appendage using AtriClip concomitant with transapical mitral valve repair using Neochord DS 1000 system is a feasible and safe treatment option in mitral valve prolapse and atrial fibrillation in patients with limited indications. However, its safety needs to be confirmed in a larger series of patients.

Arrhythmic mitral valve prolapse: a practical approach for asymptomatic patients.

Mitral valve prolapse (MVP) is usually regarded as a benign condition though the proportion of patients with a life-threatening arrhythmic MVP form remains undefined. Recently, an experts' consensus statement on arrhythmic MVP has proposed approaches for risk stratification across the spectrum of clinical manifestation. However, sudden cardiac death may be the first presentation, making clinicians focused to early unmasking this subset of asymptomatic patients. Growing evidence on the role of cardiac imaging in the in-deep stratification pathway has emerged in the last decade. Pathology findings have suggested the fibrosis of papillary muscles and inferobasal left ventricular wall as the malignant hallmark. Cardiac magnetic resonance, while of limited availability, allows the identification of this arrhythmogenic substrate. Therefore, speckle-tracking echocardiography may be a gateway to prompt referring patients to further advanced imaging investigation. Our review aims to summarize the phenotypic features linked to the arrhythmic risk and to propose an image-based algorithm intended to help stratifying asymptomatic MVP patients.

Arrhythmic risk profile in mitral valve prolapse: A systematic review and metanalysis of 1715 patients.

INTRODUCTION: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta-analysis aims to identify predictive factors for arrhythmic risk in patients with MVP. METHODS: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random-effect model as odds ratio (OR) and mean difference (MD). RESULTS: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p = .005), T-wave inversion (TWI) (OR: 2.63; p < .0001), bileaflet MVP (OR: 1.92; p < .0001) and mitral anulus disjunction (MAD) (OR: 2.60; p < .0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p < .0001), posterior mitral leaflet (MD: 2.96 mm; p < .0001), thicker AML (MD: 0.49 mm; p < .0001), longer MAD length (MD: 1.24 mm; p < .0001) and higher amount of LGE (MD: 1.41%; p < .0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13-10.96; p < .0001) compared with NAMVP. CONCLUSIONS: Our meta-analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients.