Autonomic dysregulation as a novel underlying cause of mitral valve prolapse: A hypothesis

Abstract

SummaryMitral valve prolapse is a common valvular abnormality that is caused by myxomatous degeneration, characterized macroscopically by leaflet thickening and redundancy accompanied with histologically marked proliferation of the spongiosa and mucopolysaccharide acid replacement of leaflet collagen in the prolapse leaflets. Nevertheless, the discrepant natural history and various concomitant syndromes cannot be explained completely by the current genetic autosomal dominant inheritance theory. In addition, autonomic dysregulation has been commonly reported in mitral valve prolapse, but has never been indicated as a major underlying cause. This article attempts to interpret the occurrence of primary pathology and progression in mitral valve prolapse on a common basis of improper autonomic tone. The imbalanced background of autonomic nervous firing leads to disharmonized synthetic/catabolism balance in the extracellular matrix, disrupted transition in the interstitial cellular component and invalided anti-inflammatory pathway in the endothelium, which trigger and accelerate the progression of this condition. Such a hypothesis not only unifies the seemingly disparate syndromes and valvular disorder, but also has implications for future biopharmaceutical and mechanical treatment.

A Novel Role of Sympathetic Activity in Regulating Mitral Valve Prolapse

“…tion of nerve terminals in the valve leaflet could be correlated with the mitral valve prolapse. 6 Neurotransmitters released by the SNS might be responsible for the dysfunction of nerve terminals in the valve leaflet because they act with ARs. Indeed, the enhanced expressions of ARs were found in the degenerative mitral valves, thus providing a clue when regulating progression of the mitral valve prolapse.…”

Sympathetic nervous system and cardiovascular risk in mitral valve prolapse

“…Mitral valve prolapse MVP, also known as Barlow's syndrome, is a common defect which afflicts 2-3% of the world population (9). This valvular abnormality characterised by one or both abnormal mitral leaflets in the left atrium redounds to mitral regurgitation manifested by late systolic murmur (2). The mitral regurgitation is caused by a morphological abnormality of one or more components of a complex mitral valve apparatus, i.e.…”

“…hyperadrenergic state, lowered vagal tone, and other autonomic dysfunctions (2). Most of the patients with MVP were diagnosed with initial increased sympathetic activity and excessive autonomic responsiveness (13).…”

“…This autonomic imbalance is hypothesized to be a crucial determinant at the beginning and also in progression of MVP. Autonomic dysregulation is an indicator of MVP pathogenesis and seems to be a very good predictor of miserable prognosis in MVP because of negative cases associated with congestive heart failure, progressive mitral insufficiency, thromboembolism, bacterial endocarditis, and even sudden cardiac death (2,17). These events, which appear at the terminal state in the course of aging, show up more frequently in patients with MVP (2).…”

“…A dysregulation of autonomic nervous system with exaggerated sympathetic activity could represent one of the pathological mechanisms involved in aetiology and leading to the development of this disorder. MVP has a progressive course and may finally become malignant (2). From this perspective, the evaluation of sympathetic activity might be of help.…”