Is Occult Genetic Substrate the Missing Link Between Arrhythmic Mitral Annular Disjunction Syndrome and Sudden Cardiac Death?

Appignani, Marianna; Khanji, Mohammed Y; Arbustini, Eloisa; Stuppia, Liborio; Ceriello, Laura; Girolamo, Enrico Di; Mantini, Cesare; Gallina, Sabina; Chahal, C. Anwar A.; Ricci, Fabrizio

doi:10.1016/j.cjca.2021.04.014

Cited by 13 publications

(6 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our current knowledge of genetic factors favoring the occurrence of ventricular arrhythmia in patients with MVP remains limited. 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 ).…”

Section: Arrhythmogenic Mvpmentioning

confidence: 99%

“…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. The genetic background of ventricular arrhythmia in MVP will require further investigations.…”

Section: Arrhythmogenic Mvpmentioning

confidence: 99%

See 1 more Smart Citation

Genetics and pathophysiology of mitral valve prolapse

Delwarde

Capoulade²,

Mérot³

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

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.

show abstract

Section: Arrhythmogenic Mvpmentioning

confidence: 99%

Section: Arrhythmogenic Mvpmentioning

confidence: 99%

Genetics and pathophysiology of mitral valve prolapse

Delwarde

Capoulade²,

Mérot³

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…It is therefore particularly important to focus on determining whether the syncope is related to life-threatening arrhythmia or it is noncardiac syncope will define the patient's management, with an ICD or completion of investigation with prolonged ECG monitoring or genetic testing (e.g. for long QT syndrome) in selected cases (Priori et al, 2015;Appignani et al, 2021).…”

Section: Risk Stratification For Tailored Treatment Of Syncopementioning

confidence: 99%

Risk stratification of syncope: Current syncope guidelines and beyond

Sutton

Ricci

Fedorowski

2022

Autonomic Neuroscience

Self Cite

View full text Add to dashboard Cite

Syncope is an alarming event carrying the possibility of serious outcomes, including sudden cardiac death (SCD). Therefore, immediate risk stratification should be applied whenever syncope occurs, especially in the Emergency Department, where most dramatic presentations occur. It has long been known that short-and long-term syncope prognosis is affected not only by its mechanism but also by presence of concomitant conditions, especially cardiovascular disease. Over the last two decades, several syncope prediction tools have been developed to refine patient stratification and triage patients who need expert in-hospital care from those who may receive nonurgent expert care in the community. However, despite promising results, prognostic tools for syncope remain challenging and often poorly effective.Current European Society of Cardiology syncope guidelines recommend an initial syncope workup based on detailed patient's history, physical examination supine and standing blood pressure, resting ECG, and laboratory tests, including cardiac biomarkers, where appropriate. Subsequent risk stratification based on screening of features aims to identify three groups: high-, intermediate-and low-risk. The first should immediately be hospitalized and appropriately investigated; intermediate group, with recurrent or medium-risk events, requires systematic evaluation by syncope experts; low-risk group, sporadic reflex syncope, merits education about its benign nature, and discharge. Thus, initial syncope risk stratification is crucial as it determines how and by whom syncope patients are managed. This review summarizes the crucial elements of syncope risk stratification, pros and cons of proposed risk evaluation scores, major challenges in initial syncope management, and how risk stratification impacts management of high-risk/recurrent syncope.

show abstract

“…Case reports of patients with MVP or MAD and ventricular arrhythmias have identified novel mutations in the filamin C (p.Trp34*-FLNC) and LMNA genes that may be genetic substrates for arrhythmogenic MVP/MAD syndrome. 49,50…”

Section: Potential Mechanisms For Ventricular Arrhythmias With Madmentioning

confidence: 99%

Imaging Considerations and Clinical Implications of Mitral Annular Disjunction

Drescher

Kelsey

Yankey

et al. 2022

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

Mitral annular disjunction is increasingly recognized as an important anatomic feature of mitral valve disease. The presence of mitral annular disjunction, defined as separation between the left atrial wall at the point of mitral valve insertion and the left ventricular free wall, has been associated with increased degeneration of the mitral valve and increased incidence of sudden cardiac death. The clinical importance of this entity necessitates standard reporting on cardiovascular imaging reports if patients are to receive adequate risk stratification and management. We provide a narrative review of the literature pertaining to mitral annular disjunction, its clinical implications, and areas needing further research.

show abstract

Is Occult Genetic Substrate the Missing Link Between Arrhythmic Mitral Annular Disjunction Syndrome and Sudden Cardiac Death?

Cited by 13 publications

References 3 publications

Genetics and pathophysiology of mitral valve prolapse

Genetics and pathophysiology of mitral valve prolapse

Risk stratification of syncope: Current syncope guidelines and beyond

Imaging Considerations and Clinical Implications of Mitral Annular Disjunction

Contact Info

Product

Resources

About