Mitral valve prolapse: where is the missing link?

Mitral valve prolapse (MVP), is the most common cause of primary mitral regurgitation but remains the subject of debates and gaps of knowledge regarding diagnostic criteria, prevalence and outcome. Diagnostically, the debate appeared settled in the 1980’s after the seminal description by Levine et al. of mitral annulus saddle shape and its influence on MVP diagnosis by echocardiography (1). MVP has since been defined by systolic override of one or both mitral leaflets ≥2 mm above the mitral annulus plane in parasternal long axis or apical 3 chambers view. Prevalence of MVP, based on those criteria, subsequently was estimated around 2.4% of the general population (2). However, as with any single, absolute parameter-based clinical threshold, potential neglect of less clearly defined mitral valve abnormalities, not reaching the 2 mm threshold but suggestive of MVP (thickening and/or billowing), may be a concern. These “incomplete” patterns were classified as physiologic variants of the normal mitral valve, likely not associated with adverse outcomes but were not the focus of specific studies. This “normality” notion was recently challenged in genetic studies that demonstrated the presence of these subtle abnormalities in carriers of mutations linked to MVP (3). Thus, there has been a regain of interest for these “forme fruste” phenotypes, which have been labeled as non-diagnostic forms of MVP (NDM). Presence of NDM in the context of familial MVP suggested possible pathological continuity between NDM and MVP, and NDM as a missing link between the normal valve and the fully characterized MVP. Previous work using the systematic echocardiographic examination of subjects within the Framingham cohort separated NDM patterns (4) in two categories: abnormal anterior coaptation (AAC) and minimal systolic displacement (MSD). However, NDM presence could not be extrapolated to clinical significance and long-term echocardiographic outcomes remained undefined. In the 26 April 2016 issue of Circulation, Delling et al. (5) provide further insights on echocardiographic progression of patients presenting with NDM or MVP from the 5th Framingham cohort and compared them to a reference population issued from the same cohort. After a median follow up of one decade, they observed that 80% (8 out of 10) of patients with AAC and 24% (12 out of 50) of patients with MSD had evolved to full MVP diagnostic criteria while only 1.4% (2 out of 138) of the referent population evolved to MVP.