Peripheral lymphatic vessels may not compensate for interstitial accumulation and fluid extravasation in heart failure with preserved ejection fraction (HFpEF), according to a study published in the Journal of the American College of Cardiology.

In this study, 16 patients with HFpEF (mean age, 72 years) and 16 healthy controls (mean age, 68 years) were enrolled and underwent a skin biopsy to assess vascular immunohistochemistry, gene expression, and chemical content. Additionally, study participants underwent venous occlusion plethysmography to measure the peripheral microvascular filtration coefficient for evaluating capillary fluid extravasation and isovolumetric pressure.

In participants with HFpEF, skin biopsies indicated rarefaction of small blood (P =.003) and lymphatic vessels (P =.012). In addition, residual skin lymphatics in patients with HFpEF vs healthy individuals were found to have larger diameter (P =.007) and lower expression of lymphatic differentiation and function markers (lymphatic vessel endothelial hyaluronan receptor 1, P <.05; prospero homeobox protein 1, P <.001).

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Patients with vs without HFpEF had lower microvascular filtration coefficient (calf: 3.30; interquartile range [IQR], 2.33-3.88 l x 100 ml of tissue–1 x min–1 x mm Hg–1 vs 4.66; IQR, 3.70-6.15 ml x 100 ml of tissue–1 x min–1 x mm Hg–1, respectively; P <.01; forearm: 5.16; IQR, 3.86-5.43 l x 100 ml of tissue–1 x min–1 x mm Hg–1 vs 5.66; IQR, 4.69-8.38 ml x 100 ml of tissue–1 x min–1 x mm Hg–1, respectively; P >.05). Impairment of lymphatic drainage, as indicated by differences in isovolumetric pressure, was observed in participants with HFpEF (calf: HFpEF, 16 x 4 mm Hg; no HFpEF, 22 x 4 mm Hg; P <.005; forearm: HFpEF, 17 x 4 mm Hg; no HFpEF, 25 x 5 mm Hg; P <.001).

Limitations of the study include the lack of a comorbidity-matched control population as well as the lack of head-to-head groups with and without obesity, which the researchers suggest could further define the specificity of the findings.

 “Along with demonstration of a reduced blood microvascular density in the skin, such findings draw attention to a globally and systemically defective microcirculation [in patients with HFpEF],” concluded the study authors.


Rossitto G, Mary S, McAllister C, et al. Reduced lymphatic reserve in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2020;76(24):2817-2829. doi:10.1016/j.jacc.2020.10.022