Sublingual functional capillary rarefaction in chronic heart failure

Eur J Clin Invest. 2018 Feb;48(2). doi: 10.1111/eci.12869. Epub 2017 Dec 14.


Background and objective: Microcirculatory changes contribute to clinical symptoms and disease progression in chronic heart failure (CHF). A depression of coronary flow reserve is associated with a lower myocardial capillary density in biopsies. We hypothesized that changes in cardiac microcirculation might also be reflected by a systemic reduction in capillaries and visualized by sublingual videomicroscopy. The aim was to study in vivo capillary density and glycocalyx dimensions in patients with CHF vs healthy controls.

Methods: Fifty patients with ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy age-matched subjects in a prospective cross-sectional study. Sublingual microcirculation was visualized using a sidestream darkfield videomicroscope. Functional and perfused total capillary densities were compared between patients and controls. A reduced glycocalyx thickness was measured by an increased perfused boundary region (PBR).

Results: Median functional and total perfused capillary densities were 30% and 45% lower in patients with CHF (both P < .001). Intake of oral vitamin K antagonists was associated with significantly lower capillary densities (P < .05), but not independent of NT-proBNP. Dimensions of the glycocalyx were marginally lower in CHF patients than in healthy controls (<7% difference). However, PBR correlated significantly with inflammation markers (fibrinogen: r = .58; C-reactive protein: r = .42), platelet counts (r = .36) and inversely with measures of liver/renal function such as bilirubin (r = -.38) or estimated glomerular filtration rate (r = -.34) in CHF patients.

Conclusion: CHF patients have got a markedly lower functional and total perfused capillary density in sublingual microvasculature when compared to controls, indicating a systemic decrease in microcirculation.

Keywords: capillaries; glycocalyx; heart failure; microcirculation; perfused boundary region.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Biomarkers / metabolism
  • Capillaries / diagnostic imaging
  • Capillaries / drug effects
  • Chronic Disease
  • Cross-Sectional Studies
  • Female
  • Glomerular Filtration Rate / physiology
  • Glycocalyx / physiology
  • Heart Failure / physiopathology*
  • Humans
  • Male
  • Microcirculation / physiology
  • Microscopy, Video / methods
  • Microvascular Rarefaction / physiopathology*
  • Microvessels / diagnostic imaging
  • Microvessels / physiopathology
  • Middle Aged
  • Mouth Floor / blood supply*
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • Platelet Count
  • Prospective Studies
  • Stroke Volume / physiology
  • Ventricular Dysfunction, Left / physiopathology
  • Vitamin K / antagonists & inhibitors


  • Anticoagulants
  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Vitamin K