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Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction
BACKGROUND: 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. OBJECTIVES: This s...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Biomedical
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724570/ https://www.ncbi.nlm.nih.gov/pubmed/33303070 http://dx.doi.org/10.1016/j.jacc.2020.10.022 |
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author | 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 |
author_facet | 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 |
author_sort | Rossitto, Giacomo |
collection | PubMed |
description | BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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). RESULTS: 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 < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue(–1) × min(–1) × mm Hg(–1) vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue(–1) × min(–1) × mm Hg(–1); p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue(–1) × min(–1) × mm Hg(–1) vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue(–1) × min(–1) × mm Hg(–1); p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na(+) excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001). CONCLUSIONS: Peripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target. |
format | Online Article Text |
id | pubmed-7724570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Biomedical |
record_format | MEDLINE/PubMed |
spelling | pubmed-77245702020-12-15 Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction 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 J Am Coll Cardiol Original Investigation BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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). RESULTS: 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 < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue(–1) × min(–1) × mm Hg(–1) vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue(–1) × min(–1) × mm Hg(–1); p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue(–1) × min(–1) × mm Hg(–1) vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue(–1) × min(–1) × mm Hg(–1); p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na(+) excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001). CONCLUSIONS: Peripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target. Elsevier Biomedical 2020-12-15 /pmc/articles/PMC7724570/ /pubmed/33303070 http://dx.doi.org/10.1016/j.jacc.2020.10.022 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Investigation 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 Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction |
title | Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction |
title_full | Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction |
title_fullStr | Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction |
title_full_unstemmed | Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction |
title_short | Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction |
title_sort | reduced lymphatic reserve in heart failure with preserved ejection fraction |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724570/ https://www.ncbi.nlm.nih.gov/pubmed/33303070 http://dx.doi.org/10.1016/j.jacc.2020.10.022 |
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