Prevalence and potential genetic determinants of young sudden unexplained death victims with suspected arrhythmogenic mitral valve prolapse syndrome

Giudicessi, John R.; Maleszewski, Joseph J.; Tester, David J.; Ackerman, Michael J.

doi:10.1016/j.hroo.2021.07.006

Cited by 12 publications

(7 citation statements)

References 38 publications

(74 reference statements)

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“…Only few publications have reported a potential association of MVP and pathogenic variants of the FLNC ( 60 ) or LMNA ( 61 ) genes in patients with ventricular arrhythmia. However, in a recent whole exome molecular autopsy in unexplained sudden death in young patients, MVP prevalence (7.8%) was higher than expected in the general population and pathogenic/likely pathogenic variants in cardiomyopathy-and channelopathy-susceptibility genes were over-represented ( 62 ). The frequency of MVP in the general population necessarily leads to incidental association between an inherited arrhythmia disease or a genetic variant of cardiomyopathy and MVP ( 63 ), although these factors might be synergistically associated according to the double hit theory ( 61 , 62 ) and could increase the risk of sudden death.…”

Section: Arrhythmogenic Mvpmentioning

confidence: 82%

Genetics and pathophysiology of mitral valve prolapse

Delwarde

Capoulade²,

Mérot³

et al. 2023

Front. Cardiovasc. Med.

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Mitral valve prolapse (MVP) is a common condition affecting 2–3% of the general population, and the most complex form of valve pathology, with a complication rate up to 10–15% per year in advanced stages. Complications include mitral regurgitation which can lead to heart failure and atrial fibrillation, but also life-threatening ventricular arrhythmia and cardiovascular death. Sudden death has been recently brought to the forefront of MVP disease, increasing the complexity of management and suggesting that MVP condition is not properly understood. MVP can occur as part of syndromic conditions such as Marfan syndrome, but the most common form is non-syndromic, isolated or familial. Although a specific X-linked form of MVP was initially identified, autosomal dominant inheritance appears to be the primary mode of transmission. MVP can be stratified into myxomatous degeneration (Barlow), fibroelastic deficiency, and Filamin A-related MVP. While FED is still considered a degenerative disease associated with aging, myxomatous MVP and FlnA-MVP are recognized as familial pathologies. Deciphering genetic defects associated to MVP is still a work in progress; although FLNA, DCHS1, and DZIP1 have been identified as causative genes in myxomatous forms of MVP thanks to familial approaches, they explain only a small proportion of MVP. In addition, genome-wide association studies have revealed the important role of common variants in the development of MVP, in agreement with the high prevalence of this condition in the population. Furthermore, a potential genetic link between MVP and ventricular arrhythmia or a specific type of cardiomyopathy is considered. Animal models that allow to advance in the genetic and pathophysiological knowledge of MVP, and in particular those that can be easily manipulated to express a genetic defect identified in humans are detailed. Corroborated by genetic data and animal models, the main pathophysiological pathways of MVP are briefly addressed. Finally, genetic counseling is considered in the context of MVP.

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Section: Arrhythmogenic Mvpmentioning

confidence: 82%

Genetics and pathophysiology of mitral valve prolapse

Delwarde

Capoulade²,

Mérot³

et al. 2023

Front. Cardiovasc. Med.

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“…All the studies that evaluated the relationship between SCD and MVP are retrospective (Table 1). 8,16,[18][19][20][21][22][23][24][25] In this case, the common reported features are bileaflet prolapse and the presence of thick leaflets due to excessive myxomatous tissue proliferation also known as Barlow's disease (BD) either seen with autopsy or TTE when available. MAD and myocardial fibrosis involving the papillary muscles (PMs) and mid-basal segments of the infero-lateral wall were also reported in patients with c-VA 21,[26][27][28][29] (Figure 1).…”

Section: Complex Ventricular Arrhythmias Sudden Cardiac Arrest and Mvpmentioning

confidence: 99%

Transthoracic echocardiography for arrhythmic mitral valve prolapse: Phenotypic characterization as first step

et al. 2022

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Mitral valve prolapse (MVP) is the most frequent valvulopathy with a prevalence of 1.2%–2.4% in general population and it is characterized by a benign course. Although it can be associated with some complications, ventricular arrhythmias (VA) and sudden cardiac death (SCD) as ultimate expressions, are the most worrying. The estimated risk of SCD in MVP is between 0.2% and 1.9% per year including both MVP patients with left ventricular (LV) dysfunction due to severe MR and MVP patients without significant MR. The latter ones constitute a particular phenotype called “malignant MVP” characterized by bileaflet myxomatous prolapse, ECG repolarization abnormalities and complex VAs (c‐VAs) with polymorphic/right bundle branch block morphology (RBBB) and LV fibrosis of the papillary muscles (PMs) and inferobasal wall secondary to mechanical stretching visualized as late gadolinium enhancement (LGE) areas by cardiac magnetic resonance (CMR). In MVP, the first diagnostic approach is transthoracic echocardiography (TTE) that defines the presence of mitral annular disjunction (MAD) which seems to be associated with “arrhythmic MVP” (AMVP). From an ECG point of view, AMVP is characterized by frequent premature ventricular contractions (PVCs) arising from one or both PMs, fascicular tissue, and outflow tract, as well as by T‐wave inversion in the inferolateral leads. The aim of the present paper is to describe TTE red flags that could identify MVP patients at high risk to develop complex arrhythmias as supported by the corresponding findings of LGE‐CMR and anatomy studies. TTE could be a co‐partner in phenotyping high‐risk arrhythmic MVP patients.

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“…Non-syndromic MVP is typically sporadic, but there are also familial/genetic patterns [ 29 ] where mutations in filamin A (FLNA) and Dachsous homolog-1 (DCHS-1) genes are involved [ 28 ]. Recently, exome slice sequencing analysis performed on unexplained SCD in the young (SUDY) with MVP confirmed by autopsy found a genetic variant of ryanodine receptor cardiac channel linked to arrhythmogenic and dilated cardiomyopathy [ 30 ]. Currently, genetic testing for non-syndromic MVP is not recommended due to the incomplete knowledge of the genetic background of inherited cardiovascular disease.…”

Section: Definition Of Mvp and Mitral Apparatus Associated Anomaliesmentioning

confidence: 99%

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

Vriz

Landi

Eltayeb

et al. 2023

CCR

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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.

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Prevalence and potential genetic determinants of young sudden unexplained death victims with suspected arrhythmogenic mitral valve prolapse syndrome

Cited by 12 publications

References 38 publications

Genetics and pathophysiology of mitral valve prolapse

Genetics and pathophysiology of mitral valve prolapse

Transthoracic echocardiography for arrhythmic mitral valve prolapse: Phenotypic characterization as first step

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

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