Do titin properties and myocardial fibrosis differ between hemodynamic subgroups of severe aortic stenosis and nonfailing donor hearts?
Myocardial remodeling, including titin alterations and fibrosis, is similarly severe across all hemodynamic subtypes of severe aortic stenosis, including paradoxical low-flow, low-gradient AS, which helps explain its unfavorable prognosis.
Titin-isoform expression, titin phosphorylation, and myocardial fibrosis were studied in 30 patients with severe symptomatic aortic stenosis (AS). Patients were grouped into "classical" high-gradient, normal-flow AS with preserved ejection fraction (EF); "paradoxical" low-flow, low-gradient AS with preserved EF; and AS with reduced EF. Nonfailing donor hearts served as controls. AS was associated with increased fibrosis, titin-isoform switch toward compliant N2BA, and both total and site-specific titin hypophosphorylation compared with control hearts. All AS subtypes revealed titin and matrix alterations. The extent of myocardial remodeling in "paradoxical" AS was no less severe than in other AS subtypes, thus explaining the unfavorable prognosis.
Gotzmann et al. (Fri,) studied this question.