Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation

Abstract

Background: The Fontan procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy, plastic bronchitis, and peripheral edema that may involve the lymphatic circulation. We aimed to assess lymphatic function and morphology in patients with a univentricular circulation. Methods: The functional state of lymphatic vessels in the lower extremities of patients with a Fontan circulation (n=10) was investigated using the novel technique near-infrared fluorescence imaging and compared with an age-, sex-, and weight-matched control group of healthy volunteers (n=10). The lymphatic morphology was described using T2-weighted magnetic resonance imaging, and microvascular permeability was estimated by strain gauge plethysmography. Results: The Fontan patients had 17% lower lymphatic pumping pressure (50±3.1 mm Hg) compared with controls (60±2.8 mm Hg; P =0.0341) and a 62% higher contraction frequency (0.8±0.1 min −1 ) compared with the healthy controls (0.5±0.1 min −1 ; P =0.0432). Velocity by which the lymph is moved and refill time after manual emptying of the lymphatic vessels showed no differences between the 2 groups. The thoracic duct was elongated 10% ( P =0.0409) and with an abnormal course in the Fontan patients compared with normal. No difference in microvascular permeability was found between the 2 groups. Conclusions: Patients with a Fontan circulation have an impaired lymphatic pumping capacity and morphologically changed thoracic duct. Our results indicate a challenged lymphatic vasculature in the Fontan circulation and may play a role in the pathogenesis of the complications that are seen in Fontan patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03379805.

Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction

“…Based on our results, we can only speculate as to whether a constitutive defect or a limited functional reserve of the lymphatic system is a primary predisposing factor toward an overt clinical syndrome when additional insults occur (i.e., comorbidity-driven chronic inflammation or elevated CVP) or, vice versa, a result of their long-term, potentially additive detrimental effects ( 35 , 36 ). The latter (i.e., a consequence of comorbidities and of target organ damage with diastolic dysfunction) would be in keeping with morphological changes and impaired maximal lymphatic pumping capacity reported in patients with a Fontan circulation, in whom chronically increased CVP would induce initial compensation of the afterload but long-term failure ( 26 ). Conversely, an underlying predisposing defect would remind of cases with secondary lymphedema, in which systemic alterations in lymphatic drainage precede the clinical onset of lymphedema and affect also the contralateral limbs ( 37 , 38 ).…”

“…The filtration coefficient, as well as the pressure when extravasation and lymphatic drainage balance and the net increase in tissue volume is null (i.e., the intercept of the linear association with the x-axis; P i ), were determined for each limb and participant, blindly to group allocation, by least-squares regression (Prism, version 8; GraphPad Software, San Diego, California). Limbs with <3 points free of motion artifacts for regression fitting ( 21 , 26 ) or with pre-defined limb-specific exclusion criteria were excluded from analysis.…”

Case Report: Disseminated Systemic Embolism of Lipiodol After Lymphography for Plastic Bronchitis After Fontan Repair

“…The TD is a large vessel connecting the abdominal cysterna chyli to the left subclavian vein. However, the TD is not a simple pathway as suggested by its name, but rather a multivalved contractile vessel functioning like a pump, allowing to propel fluid at a differential pressure as high as 40-70 mmHg (10,11). The junction of the TD with the subclavian vein is guarded by a valve, but in chronic venous congestion as in Fontan patients, blood may enter the dilated TD and coagulate within the lymphatic vessel.…”

Diagnosis and Management of Lymphatic Disorders in Congenital Heart Disease

“…The absence of negative inspiratory pressure during prolonged ventilation may not only reduce pulmonary blood flow and cardiac output but also add to the congestion of the venous system, increasing volume of effusions and impeding emptying of the thoracic duct [28,29]. Moreover, the lymphatic vessels in these patients are thought to be morphologically and functionally changed, further increasing the tendency to develop effusions [17,30,31]. Overall, when ventilating patients experiencing effusions and lymphatic complications, more conservative ventilator settings should be considered, or preferably early extubation when possible.…”

“…The elevated CVP impedes lymphatic return and causes lymphatic congestion. Additionally, the changed lymphatic architecture with the existence of multiple abnormal collaterals and larger more dilated lymphatic vessels may increase risk of leakage, with protein-rich fluid leaking into the low-pressure environment of the airways [30,31,98,99]. Following leakage, as the final step, an inflammatory reaction, preceded by concurrent respiratory infections or individual abnormalities in the inflammatory response causes the fibrin in the lymphatic fluid to cross-link, producing the solid casts pathognomonic of PB (Fig.…”