Morningstar JE, Gensemer C, Moore R, et al. - In patients and mice with mitral valve prolapse (MVP), the presence of prominent regional left ventricular (LV) fibrosis was evident, which backs an association between MVP and progressive damaging impacts on LV structure before overt changes in cardiac function. A reactive response of the papillary and inferobasal myocardium to elevated chordal tension from a prolapsing valve was suggested by the regionalized molecular and cellular alterations.

• Experts conducted histopathologic study of LV biopsies from peripapillary regions, inferobasal LV wall and apex on surgical patients suffering from MVP, as well as in a mouse model of human MVP.

• By histopathology of LV biopsies, there was presence of regionalized fibrosis in the peripapillary myocardium that was found to be correlated with increased macrophages and myofibroblasts.

• In MVP mouse model, experts found similar regional increases in collagen deposition that progressed over time.

• Tension‐dependent profibrotic cellular and molecular responses consistent with fibrosis locations linked with valve‐induced stress were identified in computational modeling.

• These simulations also discovered mechanosensing primary cilia as implicated in profibrotic pathways, which was validated in vitro as well as in human biopsies.

• In vitro stretching of primary human cardiac fibroblasts demonstrated that stretch not only directly activates profibrotic pathways but also elevates extracellular matrix protein generation.

• Findings raise the query if surgical intervention on MVP patients should occur earlier than suggested by current guidelines to avert advanced LV fibrosis and potentially decrease residual risk of LV dysfunction and sudden cardiac death.