Functional lymphatic reserve capacity is depressed in patients with a Fontan circulation.
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ABSTRACT: Background
Lymphatic abnormalities play a role in effusions in individuals with a Fontan circulation. Recent results using near-infrared fluorescence imaging disclosed an increased contraction frequency of lymphatic vessels in Fontan patients compared to healthy controls. It is proposed that the elevated lymphatic pumping seen in the Fontan patients is necessary to maintain habitual interstitial fluid balance. Hyperthermia has previously been used as a tool for lymphatic stress test. By increasing fluid filtration in the capillary bed, the lymphatic workload and contraction frequency are increased accordingly. Using near-infrared fluorescence imaging, the lymphatic functional reserve capacity in Fontan patients were explored with a lymphatic stress test.Methods
Fontan patients (n = 33) were compared to a group of 15 healthy individuals of equal age, weight, and gender. The function of the superficial lymphatic vessels in the lower leg during rest and after inducing hyperthermia was investigated, using near-infrared fluorescence imaging.Results
Baseline values in the Fontan patients showed a 57% higher contraction frequency compared to the healthy controls (0.4 ± 0.3 min-1 vs. 0.3 ± 0.2 min-1 , p = 0.0445). After inducing stress on the lymphatic vessels with hyperthermia the ability to increase contraction frequency was decreased in the Fontan patients compared to the controls (0.6 ± 0.5 min-1 vs. 1.2 ± 0.8 min-1 , p = 0.0102).Conclusions
Fontan patients had a higher lymphatic contraction frequency during normal circumstances. In the Fontan patients, the hyperthermia response is dampened indicating that the functional lymphatic reserve capacity is depressed. This diminished reserve capacity could be part of the explanation as to why some Fontan patients develop late-onset lymphatic complications.
SUBMITTER: Mohanakumar S
PROVIDER: S-EPMC8165731 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7720935 | biostudies-literature
Project description:BackgroundThe Fontan procedure is currently the mainstay therapy for single functional ventricles. However, with prolonged follow-up duration, various complications have been observed that seriously influence the quality of life of patients.ObjectivesThe aim of this meta-analysis is to compare the effectiveness of pharmacologic agents in improving exercise capacity in patients with Fontan circulation.MethodsThis meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and has been registered in the International Prospective Register for Systematic Reviews database with registration no. 282352. Quality assessments of the included studies were assessed using the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement.ResultsTwelve studies met the predetermined inclusion criteria and were included in this metaanalysis. This meta-analysis found that treatment with bosentan significantly improved New York Heart Association Functional Class (NYHA FC) in Fontan patients (standard mean difference - 0.59, 95% CI -0.94 - -0.25; P=0.0008; I2 = 1%). However, the use of bosentan (P=0.66) and sildenafil (P=0.13) did not show a significant improvement in the maximum rate of oxygen consumption (VO2 max).ConclusionThis meta-analysis shows that people with Fontan circulation may benefit from using bosentan as it decreases postexercise heart rate and improves NYHA FC and 6-minute walking test results. Therefore, indirectly improving exercise capacity. Nonetheless, considerable work is required to strengthen our knowledge in improving the exercise capacity of Fontan patients.
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Project description:The Fontan procedures, designed to treat paediatric patients with functional single ventricles, have markedly improved the patient's survival into adulthood. The physiology of the Fontan circuit inevitably increases systemic venous pressure, which may lead to multi-system organ failure in the long-term follow-up. Fontan-associated liver disease (FALD) can progress to liver cirrhosis with signs of portal hypertension. Focal nodular hyperplasia-like nodules commonly develop in FALD. Imaging surveillance is often performed to monitor the progression of FALD and to detect hepatocellular carcinoma, which infrequently develops in FALD. Other abdominal abnormalities in post-Fontan patients include protein losing enteropathy and pheochromocytoma/paraganglioma. Given that these abdominal abnormalities are critical for patient management, it is important for radiologists to become familiar with the abdominal abnormalities that are common in post-Fontan patients on cross-sectional imaging. TEACHING POINTS:• Fontan procedure for functional single ventricle has improved patient survival into adulthood. • Radiologists should be familiar with unique imaging findings of Fontan-associated liver disease. • Focal nodular hyperplasia-like nodules commonly develop in Fontan-associated liver disease. • Hepatocellular carcinoma, protein-losing enteropathy, pheochromocytoma/paraganglioma may develop.
| S-EPMC5991003 | biostudies-literature
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| S-EPMC6512107 | biostudies-literature
Project description:Few studies have investigated how the Fontan circulation affects lung function, and no studies have investigated the development of lung function over longer time in these patients. We aimed to describe the development of lung function in Fontan patients over a 10-year period. Pulmonary function tests (PFT), including spirometry and diffusion capacity for Carbon Monoxide (DLCO) and Nitric Oxide (DLNO), were conducted in a Danish Fontan cohort in 2011 (PFT-I). In 2021, re-investigations were performed (PFT-II). We investigated changes in percent predicted (%pred) lung function from PFT-I to PFT-II. Patients were categorized into a pediatric group (age under 18 at PFT-I) and an adult group (age 18 or older at PFT-I). Out of the 81 patients completing PFT-I, 48 completed PFT-II. In the pediatric group (32 patients), there were significant declines in %pred forced expiratory volume in 1s (99.7 (92.4, 104.4)-89.3 (84.9, 97.2), p < 0,001), forced vital capacity (98.3 (87.8, 106.1)-96.7 (86.7, 100.6), p = 0.008), and alveolar volume (95.5 (89.5, 101.6)-89.5 (79.7, 93.2), p < 0.001). The corresponding measurements remained stable in the adult group. However, the median %pred DLNO significantly declined in the adult group (58.4 (53.3, 63.5)-53.7 (44.1, 57.3), p = 0.005). Over a 10-year period, several lung function parameters declined significantly in the younger Fontan patients, suggesting possible impairments in lung development during growth. The decline in %pred DLNO in the adult patient group indicates deterioration of the membrane component of diffusion capacity, implying that the Fontan circulation might negatively affect the alveolar membrane over time.
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Project description:Key pointsThe distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients. Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology.AbstractMany factors affect the distribution of pulmonary perfusion, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. An example is following the Fontan procedure, where pulmonary perfusion is passive, and heterogeneity may be increased because of the underlying pathophysiology leading to Fontan palliation, remodelling, or increased gravitational gradients from low flow. Another is pulmonary arterial hypertension (PAH), where gravitational gradients may be reduced secondary to high pressures, but remodelling may increase perfusion heterogeneity. We evaluated regional pulmonary perfusion in Fontan patients (n = 5), healthy young controls (Fontan control, n = 5), patients with PAH (n = 6) and healthy older controls (PAH control) using proton magnetic resonance imaging. Regional perfusion was measured using arterial spin labelling. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Mean perfusion was similar (Fontan = 2.50 ± 1.02 ml min-1 ml-1 ; Fontan control = 3.09 ± 0.58, PAH = 3.63 ± 1.95; PAH control = 3.98 ± 0.91, P = 0.26), and the slopes of gravitational gradients were not different (Fontan = -0.23 ± 0.09 ml min-1 ml-1 cm-1 ; Fontan control = -0.29 ± 0.23, PAH = -0.27 ± 0.09, PAH control = -0.25 ± 0.18, P = 0.91) between groups. Perfusion relative dispersion was greater in both Fontan and PAH than controls (Fontan = 1.46 ± 0.18; Fontan control = 0.99 ± 0.21, P = 0.005; PAH = 1.22 ± 0.27, PAH control = 0.91 ± 0.12, P = 0.02) but similar between patient groups (P = 0.13). These findings persisted after removing contributions from large blood vessels and gravitational gradients (all P < 0.05). We conclude that patients with Fontan physiology and PAH have increased pulmonary perfusion heterogeneity that is not explained by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects the effects of remodelling in PAH and possibly in Fontan physiology.
| S-EPMC8315789 | biostudies-literature
Project description:BackgroundSeveral clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification.Methods and resultsData on patients with Fontan circulation who had a CMR study from January 2002 to January 2011 were retrospectively reviewed. The end point was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years (25th, 75th percentiles: 14, 26) with a median age at Fontan of 3.6 years (2.3, 7.1). During a median post-CMR follow-up period of 4.1 years (2.6, 6.2), 24 patients (11%) reached the end point: 20 deaths, 3 transplantations, and 1 transplantation listing. In a multivariable Cox regression model with clinical parameters only, protein-losing enteropathy was associated with death or listing for transplant. A multivariable model, including clinical and CMR parameters, showed that in addition to protein-losing enteropathy, ventricular indexed end-diastolic volume >125 mL/body surface area raised to the 1.3 power was associated with the endpoint. A likelihood-ratio test comparing the 2 models showed that the addition of indexed end-diastolic volume resulted in a significantly improved end point prediction (P<0.001)-C-index increased from 0.63 to 0.79.ConclusionsCMR-derived ventricular indexed end-diastolic volume is an independent predictor of death or transplant in patients late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification.
| S-EPMC4262249 | biostudies-literature
Project description:Galectin-3 may play a role in cardiac and noncardiac fibrosis, and elevated circulating levels of this protein predict adverse outcomes in patients with heart failure who do not have congenital heart disease. We investigated galectin-3 in adults with single-ventricle Fontan circulation, patients who are prone to premature clinical deterioration in the context of extensive multiorgan fibrosis.We measured plasma galectin-3 concentrations in 70 ambulatory adult Fontan patients and 21 age- and sex-matched control participants. Galectin-3 level was significantly higher in the Fontan group (11.85 ng/mL, interquartile range 9.9 to 15.0 ng/mL) versus the control group (9.4 ng/mL, interquartile range 8.2 to 10.8 ng/mL; P<0.001). Among Fontan patients, galectin-3 was positively correlated with age, uric acid, and high-sensitivity C-reactive protein and negatively correlated with estimated glomerular filtration rate. There was no significant relationship between galectin-3 and oxygen saturation, Fontan type, or ventricular morphology. Over a median follow-up of 461 days, 15 events occurred among the Fontan patients: 12 nonelective hospitalizations (with 2 subsequent deaths) and 3 deaths without prior hospitalization. Patients with elevated galectin-3 (n=19, defined as >2 SD above the control group mean value) had a higher risk of nonelective hospitalization or death (hazard ratio 6.0, 95% CI 2.1 to 16.8, P<0.001). This relationship persisted after individual adjustment for covariates including age, New York Heart Association functional class, C-reactive protein, and estimated glomerular filtration rate and after multivariable adjustment for independently predictive covariates (hazard ratio 9.2, 95% CI 2.4 to 35.2, P=0.001).Galectin-3 concentrations are elevated among adults with a Fontan circulation, and elevated galectin-3 is associated with an increased risk of nonelective cardiovascular hospitalization or death.
| S-EPMC4859390 | biostudies-other
Project description:ObjectivesTo define whether adults with a Fontan circulation, who have lifelong venous congestion and limited cardiac output, have impaired glomerular filtration rate (GFR) or elevated urinary biomarkers of kidney injury.MethodsWe measured circulating cystatin C and creatinine (n=70) and urinary creatinine, albumin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl glucosaminidase (NAG) (n=59) in ambulatory adult Fontan patients and 20 age-matched and sex-matched controls. Urinary biomarkers were normalised to urine creatinine concentration. Survival free from non-elective cardiovascular hospitalisation was compared by estimated GFR and urinary biomarker levels using survival analysis.ResultsCystatin C GFR was lower in the Fontan group compared with controls (114.2±22.8 vs 136.3±12.8 mL/min/1.73 m2, p<0.0001); GFR<90 mL/min/1.73 m2 in 14.3% vs 0% of controls. Albumin-to-creatinine ratio (ACR), KIM-1 and NAG were elevated compared with controls; ACR=23.2 (7.6-38.3) vs 3.6 (2.5-5.7) mg/g, p<0.0001; NAG=1.8 (1.1-2.6) vs 1.1 (0.9-1.6) U/g, p=0.02; KIM-1=0.91 (0.52-1.45) vs 0.33 (0.24-0.74) ng/mg, p=0.001. Microalbuminuria, ACR>30 mg/g, was present in 33.9% of the Fontan patients but in none of the controls. Over median 707 (IQR 371-942)-day follow-up, 31.4% of patients had a clinical event. Higher KIM-1 and NAG were associated with higher risk of non-elective hospitalisation or death (HR/+1 SD=2.1, 95% CI 1.3 to 3.3, p=0.002; HR/+1 SD=1.6, 95% CI 1.05 to 2.4, p=0.03, respectively); cystatin C GFR was associated with risk of the outcome (HR/+1 SD=0.66, 95% CI 0.48 to 0.90, p=0.009) but creatinine-based GFR was not (HR/+1 SD=0.91, 95% CI 0.61 to 1.38, p=0.66). Neither ACR nor NGAL was associated with events.ConclusionsThe Fontan circulation is commonly associated with reduced estimated GFR and evidence for glomerular and tubular injury. Those with lower cystatin C GFR and tubular injury are at increased risk of adverse outcomes.
| S-EPMC5500305 | biostudies-literature