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.

Considerations & challenges of mitral valve repair in females: diagnosis, pathology, and intervention.

PURPOSE OF REVIEW: Disparities in mitral valve (MV) repair outcomes exist between men and women. This review highlights sex-specific differences in MV disease aetiology, diagnosis, as well as timing and type of intervention. RECENT FINDINGS: Females present with more complicated disease: anterior or bileaflet prolapse, leaflet dysplasia/thickening, mitral annular calcification, and mixed mitral lesions. The absence of indexed echocardiographic mitral regurgitation (MR) severity parameters contributes to delayed intervention in women, resulting in more severe symptom burden at time of surgery. The sequelae of chronic MR also necessitate concomitant procedures (e.g. tricuspid repair, arrhythmia surgery) at the time of mitral surgery. Complex MV pathology, greater patient acuity, and more complicated procedures collectively pose challenges to successful MV repair and postoperative recovery. As a consequence, women receive disproportionately more MV replacement than men. In-hospital mortality after MV repair is also greater in women than men. Long-term outcomes of MV repair are comparable after risk-adjustment for preoperative status; however, women experience a greater incidence of postoperative heart failure. SUMMARY: To address the inequity in MV repair outcomes between sexes, indexed diagnostic measurements, diligent surveillance of asymptomatic MR, increased recruitment of women in large clinical trials, and mandatory reporting of sex-based subgroup analyses are recommended.

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.

Effects of Mitral Valve Surgery on Ventricular Arrhythmia in Mitral Valve Prolapse Patients: Five-Year Eollow-up.

Aim      To evaluate the effect of mitral valve (MV) repair and replacement on the incidence of ventricular arrhythmias (VA) and to identify risk factors for the persistence of VA in patients with MV prolapse and severe mitral regurgitation (MR) during a mid-term follow-up.Material and methods  A single-site observational, prospective study successively enrolled 30 patients (mean age, 55.2±9.9 years, 60% men) who underwent MV repair or replacement for severe MR due to MV prolapse or chordal avulsion. Transthoracic echocardiography and Holter monitoring were performed in all patients before and annually after surgery. A pathomorphological study of MV fragments excised during surgery was performed.Results During the five-year follow-up period (144 person-years), one case of sudden cardiac death outside a health care facility was recorded. MR severity progressed in three patients after MV repair. The total number of all VAs decreased during the follow-up period, with a significant decrease in the number of paroxysms of unstable ventricular tachycardia during the first two years after surgery. The presence of VA in the postoperative period was correlated with the severity of postoperative left ventricular (LV) remodeling: end-diastolic volume (EDV) (rs=0.69; p=0.005), LV ejection fraction (EF) (rs = -0.55; p=0.004) and severity of MV myxomatous alterations according to histological study data (rτ=0.58; p=0.045). The beta-blocker treatment did not influence the VA frequency and severity (rs= -0.18; p=0.69). According to a univariate regression analysis only EDV (p = 0.001), LVEF <50% (p = 0.003), and myxomatous MV degeneration (p = 0.02) were risk factors for persistent ventricular tachycardia in the postoperative period.Conclusion      Surgical intervention on MV in patients with MV prolapse and severe MR decreased the number of cases of malignant VAs and was correlated with the postoperative changes in LV volume and function, as well as the severity of MV myxomatous alterations.

Lifetime exercise dose and ventricular arrhythmias in patients with mitral valve prolapse.

AIMS: Patients with mitral valve prolapse (MVP) have high risk of life-threatening ventricular arrhythmias (VAs). Data on the impact of exercise on arrhythmic risk in these patients are lacking. We explored whether lifetime exercise dose was associated with severe VA and with established risk factors in patients with MVP. Furthermore, we explored the circumstances at the VA event. METHODS AND RESULTS: In this retrospective cohort study, we included patients with MVP and assessed lifetime exercise dose as metabolic equivalents of task (MET) hours/week. Severe VA was defined as sustained ventricular tachycardia or fibrillation, aborted cardiac arrest, and appropriate shock by a primary preventive implantable cardioverter defibrillator. We included 136 MVP patients (48 years [interquartile range (IQR) 35-59], 61% female), and 17 (13%) had previous severe VA. The lifetime exercise dose did not differ in patients with and without severe VA (17 MET h/week [IQR 9-27] vs. 14 MET h/week [IQR 6-31], P = 0.34). Lifetime exercise dose > 9.6 MET h/week was a borderline significant marker for severe VA (OR 3.38, 95% CI 0.92-12.40, P = 0.07), while not when adjusted for age (OR 2.63, 95% CI 0.66-10.56, P = 0.17). Ventricular arrhythmia events occurred most frequently during wakeful rest (53%), followed by exercise (29%) and sleep (12%). CONCLUSION: We found no clear association between moderate lifetime exercise dose and severe VA in patients with MVP. We cannot exclude an upper threshold for safe levels of exercise. Further studies are needed to explore exercise and risk of severe VA.

The Prevalence and Characteristics of Arrhythmic Mitral Valve Prolapse in Patients With Unexplained Cardiac Arrest.

BACKGROUND: There is growing evidence that mitral valve prolapse (MVP) is associated with otherwise unexplained cardiac arrest (UCA). However, reports are hindered by the absence of a systematic ascertainment of alternative diagnoses. OBJECTIVES: This study reports the prevalence and characteristics of MVP in a large cohort of patients with UCA. METHODS: Patients were enrolled following an UCA, defined as cardiac arrest with no coronary artery disease, preserved left ventricular ejection fraction, and no apparent explanation on electrocardiogram. A comprehensive evaluation was performed, and patients were diagnosed with idiopathic ventricular fibrillation (IVF) if no cause was found. Echocardiography reports were reviewed for MVP. Patients with MVP were divided into 2 groups: those with IVF (AMVP) and those with an alternative diagnosis (nonarrhythmic MVP). Patient characteristics were then compared. The long-term outcomes of AMVP were reported. RESULTS: Among 571 with an initially UCA, 34 patients had MVP (6%). The prevalence of definite MVP was significantly higher in patients with IVF than those with an alternative diagnosis (24 of 366 [6.6%] vs 5 of 205 [2.4%]; P = 0.03). Bileaflet prolapse was significantly associated with AMVP (18 of 23 [78%] vs 1 of 8 [12.5%]; P = 0.001; OR: 25.2). The proportion of patients with AMVP who received appropriate implantable cardioverter-defibrillator therapies over a median follow-up of 42 months was 21.1% (4 of 19). CONCLUSIONS: MVP is associated with otherwise UCA (IVF), with a prevalence of 6.6%. Bileaflet prolapse appears to be a feature of AMVP, although future studies need to ascertain its independent association. A significant proportion of patients with AMVP received appropriate implantable cardioverter-defibrillator therapies during follow-up.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Increased incidence of mitral valve prolapse in children with pectus chest wall deformity.

BACKGROUND: Pectus anomalies constitute 95% of chest anomalies. Pectus carinatum (PC) and excavatum (PE) are often asymptomatic in childhood. However, symptoms and signs such as chest pain, dyspnea, and mitral valve prolapse (MVP) can be seen in pectus anomalies. Demographic characteristics and accompanying cardiac signs in children with pectus deformity were investigated. METHODS: In this study, the clinical findings for children with pectus deformity, and the incidence of MVP and other concomitant heart diseases detected in echocardiographic examinations were evaluated. RESULTS: Eighty-two children with PE, 27 with PC, and 107 healthy children were included in this study. In the echocardiographic examination of PE, PC patients, and healthy children, MVP was detected with frequencies of 25%, 33%, and 2% respectively. CONCLUSIONS: The study showed that pectus anomalies were associated with an increased incidence of MVP. All patients with pectus deformity should therefore undergo a screening echocardiogram in adolescence to assess for the presence of MVP.

Perforated posterior mitral valve leaflet in mitral annular disjunction and infective endocarditis.

We herein presented a 17-year-old female with history of mild mitral valve prolapse who was admitted for methicillin-sensitive Staphylococcus aureus endocarditis and diagnosed with mitral annular disjunction and perforated posterior mitral valve leaflet on two-dimensional and three-dimensional echocardiography (P1-P2). A perforation in the posterior leaflet was confirmed and repaired during surgical intervention. This is a rare presentation of leaflet perforation in the area of mitral annular disjunction.

Acute mitral regurgitation with and without acute heart failure.

Acute severe mitral regurgitation (MR) is rare, but often leads to cardiogenic shock, pulmonary edema, or both. Most common causes of acute severe MR are chordae tendineae (CT) rupture, papillary muscle (PM) rupture, and infective endocarditis (IE). Mild to moderate MR is often seen in patients with acute myocardial infarction (AMI). CT rupture in patients with floppy mitral valve/mitral valve prolapse is the most common etiology of acute severe MR today. In IE, native or prosthetic valve damage can occur (leaflet perforation, ring detachment, other), as well as CT or PM rupture. Since the introduction of percutaneous revascularization in AMI, the incidence of PM rupture has substantially declined. In acute severe MR, the hemodynamic effects of the large regurgitant volume into the left atrium (LA) during left ventricular (LV) systole, and in turn back into the LV during diastole, are profound as the LV and LA have not had time to adapt to this additional volume. A rapid, but comprehensive evaluation of the patient with acute severe MR is essential in order to define the underline cause and apply appropriate management. Echocardiography with Doppler provides vital information related to the underlying pathology. Coronary arteriography should be performed in patients with an AMI to define coronary anatomy and need for revascularization. In acute severe MR, medical therapy should be used to stabilize the patient before intervention (surgery, transcatheter); mechanical support is often required. Diagnostic and therapeutic steps should be individualized, and a multi-disciplinary team approach should be utilized.

[Barlow syndrome: A rare etiology of sudden death]. / Síndrome de Barlow: causa olvidada de miocardiopatía dilatada y muerte súbita.

We present the case of a 60-year-old woman, with a history of mitral valve prolapse, who consulted for dyspnea and palpitations of 2 weeks of evolution up to functional class IV. The admission electrocardiogram showed a moderately responsive atrial fibrillation rhythm with frequent ventricular extra systoles. A transthoracic echocardiogram was performed which showed mitral valve prolapse with severe impairment of ventricular function. Barlow syndrome was diagnosed. During hospitalization, the patient presented three episodes of cardiorespiratory arrest that were reversed with advanced cardiopulmonary resuscitation maneuvers. During admission, a negative balance was performed, sinus rhythm was reverted and an implantable automatic defibrillator was placed in secondary prevention. During follow-up, severe deterioration of ventricular function persisted. We highlight Barlow syndrome as a rare cause of sudden death and its association with dilated cardiomyopathy.

Se presenta el caso de una mujer de 60 años, con antecedente de prolapso de la válvula mitral, que consultó por disnea y palpitaciones de 2 semanas de evolución hasta clase funcional IV. En el electrocardiograma de ingreso se evidenció ritmo de fibrilación auricular de moderada respuesta con extrasístoles ventriculares frecuentes. Se realizó ecocardiograma transtorácico donde se observó prolapso de la válvula mitral con deterioro grave de la función ventricular. Se diagnosticó síndrome de Barlow. La paciente intercurrió durante la internación con tres episodios de paro cardiorrespiratorio que revirtieron con maniobras de reanimación cardiopulmonar avanzada. Durante la internación se realizó balance negativo, se revirtió a ritmo sinusal y se colocó cardiodesfibrilador implantable en prevención secundaria. En el seguimiento persiste con deterioro grave de la función ventricular. Destacamos el síndrome de Barlow como una causa poco frecuente de muerte súbita y su asociación con miocardiopatía dilatada.

How many clues make an evidence? An unusual case of aborted cardiac arrest due to mitral valve prolapse.

There is an increasing awareness on the association between mitral valve prolapse (MVP) and sudden cardiac death. Mitral annular disjunction (MAD) is a phenotypic risk feature that can help in risk stratification. We present a case of a 58-year-old woman who experienced an out-of-hospital cardiac arrest caused by ventricular fibrillation interrupted by a direct current shock. No coronary lesions were documented. Echocardiogram showed myxomatous MVP. Nonsustained ventricular tachycardia have been registered during hospital stay. Interestingly, cardiac magnetic resonance revealed MAD and a late gadolinium enhancement area in inferior wall. Finally, a defibrillator has been implanted. For arrhythmic risk stratification of MVP with MAD, multimodality imaging is the diagnostic tool to find out the disease behind many cardiac arrests of unknown cause.

Arrhythmic Mitral Valve Prolapse: Risk Assessment and Management.

Arrhythmic mitral valve prolapse (MVP) has gained great interest recently because of the increasing recognition of its potential role in unexplained cardiac arrest. Although evidence has accumulated to show the association of arrhythmic MVP (AMVP) with sudden cardiac death (SCD), risk stratification and management remain unclear. Physicians are faced with the challenges of screening for AMVP among MVP patients and the dilemma of when and how to intervene to prevent SCD in these patients. In addition, there is little guidance to help approach MVP patients who present with an otherwise unexplained cardiac arrest to know whether MVP was the primary cause of cardiac arrest or just an innocent bystander. Herein we review the epidemiology and definition of AMVP, the risk and mechanisms of SCD, and summarize the clinical evidence behind risk markers of SCD and therapeutic interventions that could potentially prevent it. We also propose an algorithm that provides guidance as to how to screen for AMVP and what therapeutic interventions to use. Last, we propose a diagnostic algorithm for approaching patients with otherwise unexplained cardiac arrest who are shown to have MVP.

Can cartilage intermediate layer protein 1 (CILP1) use as a novel biomarker for canine myxomatous mitral valve degeneration levels or not?

BACKGROUND: Myxomatous mitral valve degeneration (MMVD) is the most common degenerative heart disease in dogs and is associated with irreversible changes in the valve tissue. Although traditional cardiac biomarkers are efficient for diagnosing MMVD, there are limitations, therefore, it is important to find novel biomarkers. Cartilage intermediate layer protein 1 (CILP1), an extracellular matrix-derived protein, acts as a transforming growth factor-ß antagonist and is involved in myocardial fibrosis. This study aimed to evaluate serum CILP1 levels in canines with MMVD. Dogs with MMVD were staged according to the American College of Veterinary Internal Medicine consensus guidelines. Data analysis was performed using the Mann-Whitney U test, Spearman's correlation, and receiver operating characteristic (ROC) curves. RESULTS: CILP1 levels were elevated in dogs with MMVD (n = 27) compared to healthy controls (n = 8). Furthermore, results showed that CILP1 levels were significantly higher in stage C group dogs compared to healthy controls. The ROC curve of CILP1 and NT-proBNP were good predictors of MMVD, although no similarity was observed between the two. Left ventricular end-diastolic diameter normalized to the body weight (LVIDdn) and left atrial to aorta dimension (LA/Ao) showed a strong association with CILP1 levels; however, no correlation was observed between CILP1 levels and vertebral heart size (VHS) and vertebral left atrial score (VLAS). The optimal cut-off value was selected from the ROC curve and dogs were classified according to the cut-off value (1.068 ng/mL, sensitivity 51.9%, specificity 100%). Results showed a significant association of CILP1 with cardiac remodeling indicators, such as VHS, VLAS, LA/Ao, and LVIDdn. CONCLUSIONS: CILP1 can be an indicator of cardiac remodeling in canines with MMVD and therefore, can be used as an MMVD biomarker.

Characterization of ventricular arrhythmias and sudden cardiac death in subjects with mitral valve prolapse and mitral annular disjunction.

Sudden cardiac death is reported as the leading cause of mortality in developed nations. Arrhythmic mitral valve disease, encompassing mitral valve prolapse and/or mitral annular disjunction, is thought to be responsible in a sizable portion of these deaths. Despite this evidence, there are no reliable methods or clinically useful risk stratification schemes to determine which group of patients are at higher risk or may benefit from interventions such as catheter ablation or prophylactic implantation of a defibrillator. The reasons for this lack of guidance include our incomplete understanding of the mechanisms of ventricular arrhythmias and the fact that mitral valve prolapse and disjunction are frequently diagnosed, yet carry an overall low risk of sudden cardiac death. This heterogeneity makes the development of a reliable prediction model based on the presence of common risk factors very difficult. In this review, we summarize the relevant literature regarding the epidemiology, diagnosis, pathophysiology, and management of mitral valve prolapse and mitral annular disjunction and elucidate their role in sudden cardiac death.

Mitral Annular Elasticity Determines Severity of Regurgitation in Barlow's Mitral Valve Disease.

OBJECTIVES: Barlow's mitral valve disease with late systolic mitral regurgitation provides diagnostic and therapeutic challenges. The mechanisms of the regurgitation are still unclear. We hypothesized that the onset and the severity of late systolic regurgitation are determined by annulus dynamics and the mechanical stresses imposed by the left ventricle. METHODS: Ten patients with Barlow's mitral valve disease and mitral annulus disjunction (MAD) were compared with 10 healthy controls. Resting blood pressure was measured, and transthoracic three-dimensional echocardiography was analyzed using a holographic display that allows tracking and measurements of mitral annulus surface area (ASA) throughout the cardiac cycle. A novel annulus elastance index (dASA/dP) was calculated between aortic valve opening and onset of mitral regurgitation. Severity of MAD was quantified as the disjunction index (mm × degree). Leaflet coaptation area was calculated using a finite element model. RESULTS: Peak systolic ASAs in controls and patients were 9.3 ± 0.6 and 21.1 ± 3.1 cm2, respectively (P < .001). In patients, the ASA increased rapidly during left ventricular ejection, and onset of mitral regurgitation coincided closely with peak upslope of annulus area change (dASA/dt). The finite element model showed a close association between rapid annulus displacement and coaptation area deficit in Barlow's mitral valve disease. Systolic annulus elastance index (0.058 ± 0.036 cm2/mm Hg) correlated strongly with disjunction index (r = 0.91, P < .0001). Moreover, regurgitation volume showed a positive correlation with systolic blood pressure (r = 0.80, P < .01). CONCLUSION: The present pilot study supports the hypothesis that annulus dilatation may accentuate mitral valve regurgitation in patients with Barlow's mitral valve disease. A novel annulus elastance index may predict the severity of mitral valve regurgitation in selected patients.

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.