Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction

Microvascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated. This study aimed to investigat...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2020-12, Vol.76 (24), p.2817-2829
Main Authors: Rossitto, Giacomo, Mary, Sheon, McAllister, Christine, Neves, Karla Bianca, Haddow, Laura, Rocchiccioli, John Paul, Lang, Ninian Nicholas, Murphy, Clare Louise, Touyz, Rhian Merry, Petrie, Mark Colquhoun, Delles, Christian
Format: Article
Language:English
Subjects:
Aged
Case-Control Studies
Female
Heart Failure - metabolism
Heart Failure - physiopathology
Humans
Lymphatic Vessels - physiopathology
Male
Microvessels - physiopathology
Middle Aged
Original Investigation
Skin - blood supply
Skin - metabolism
Sodium - metabolism
Stroke Volume
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Summary:Microvascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated. This study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na excess. Patients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na , and K ) analyses; and 2) venous occlusion plethysmography to assess peripheral microvascular filtration coefficient (measuring capillary fluid extravasation) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation). Skin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p 
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2020.10.022