Venous congestion and pulmonary vascular function in Fontan circulation: Implications for prognosis and treatment.
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ABSTRACT:
SUBMITTER: Egbe AC
PROVIDER: S-EPMC6146405 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Venous congestion and pulmonary vascular function in Fontan circulation: Implications for prognosis and treatment.
Egbe Alexander C AC Reddy Yogesh N V YNV Khan Arooj R AR Al-Otaibi Mohamad M Akintoye Emmanuel E Obokata Masaru M Borlaug Barry A BA
International journal of cardiology 20181101
<h4>Background</h4>Elevation in central venous pressure (CVP) plays a fundamental pathophysiologic role in Fontan circulation. Because there is no sub-pulmonary ventricle in this system, CVP also provides the driving force for pulmonary blood flow. We hypothesized that this would make Fontan patients more susceptible to even low-level elevation in pulmonary vascular resistance index (PVRI), resulting in greater systemic venous congestion and adverse outcomes.<h4>Methods</h4>Adult Fontan patients ...[more]
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Project description:BackgroundPulmonary vascular disease, pulmonary endothelial dysfunction, liver fibrosis, renal disease, and exercise intolerance are common in adults with Fontan physiology. Although the pathophysiologic mechanisms linking these phenomena have been studied, certain aspects are not well understood.ObjectivesThis study hypothesized that impaired pulmonary vascular reserve (VR) plays a central role linking these abnormalities, and that patients with abnormal pulmonary VR with exercise, compared with patients with normal VR, would display poorer pulmonary endothelial function, greater liver stiffness, more renal dysfunction, and poorer exercise capacity.MethodsSymptomatic adults with the Fontan palliation (n = 29) underwent invasive cardiopulmonary exercise testing, echocardiography, and assessment of microvascular function. Abnormal pulmonary VR was defined by the slope of increase in pulmonary pressure relative to cardiac output with exercise >3 mm Hg/l/min. Pulmonary endothelial function was assessed using reactive hyperemia index. End-organ function was assessed using magnetic resonance elastography-derived liver stiffness, glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and peak oxygen consumption (Vo2).ResultsCompared with individuals with normal VR (n = 8), those with abnormal VR (n = 21) displayed higher central and pulmonary venous pressures, and more severely impaired cardiac output and stroke volume responses to exertion, but similar pulmonary vascular resistance at rest. Patients with abnormal VR displayed more severely impaired reactive hyperemia index, increased liver stiffness, lower glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, and lower peak Vo2. As compared to pulmonary vascular resistance at rest, slope of increase in pulmonary pressure relative to cardiac output displayed stronger correlations with reactive hyperemia index (r = -0.63 vs. r = -0.31; Meng test p = 0.009), magnetic resonance elastography-derived liver stiffness (r = 0.47 vs. r = 0.29; Meng test p = 0.07), glomerular filtration rate (r = -0.52 vs. r = -0.24; Meng test p = 0.03), N-terminal pro-B-type natriuretic peptide (r = 0.56 vs. r = 0.17; Meng test p = 0.02), and peak Vo2 (r = -0.63 vs. r = -0.26; Meng test p = 0.02).ConclusionsPulmonary vascular limitations in Fontan physiology are related to pulmonary endothelial and end-organ dysfunction, suggesting a mechanistic link between these commonly observed findings, and these abnormalities are more apparent during exercise testing, with little relationship at rest.
| S-EPMC7720935 | biostudies-literature
Project description:Pulmonary venous (PV) obstruction is associated with a poor prognosis, as well as a high risk of recurrence, following surgical treatment. It can also interfere with the successful completion of Fontan circulation in patients with complex congenital heart disease. A case of a patient who had right isomerism (also known as asplenia syndrome), total anomalous pulmonary venous connection (TAPVC), and a single right ventricle is presented. Although bilateral total occlusion of the inferior PVs was identified postoperatively, the formation of the anastomosis and collateral vessels into the superior and middle PVs enabled successful completion of Fontan circulation. Anastomoses and collateral flow of the PVs were found largely in the interlobar pleura and not in the lung parenchyma.
| S-EPMC6477765 | biostudies-literature
Project description:ObjectiveFontan circulation maintains preload and cardiac output by reducing venous capacitance and increasing central venous pressure (CVP). The resultant congestive end-organ damage affects patient prognosis. Therefore, a better circulatory management strategy to ameliorate organ congestion is required in patients with Fontan circulation. We sought to verify whether aggressive arterial and venous dilation therapy in addition to pulmonary dilation (super-Fontan strategy) can improve Fontan circulation and reduce congestion.MethodsPatients after Fontan surgery who received the super-Fontan strategy in a single center were recruited. Participants were examined using medical records between 2010 and 2018. We retrospectively analyzed the changes in hemodynamics at rest and during treadmill exercise before and after the introduction of this therapy.ResultsThe therapy significantly increased venous capacitance (3.21 ± 1.27 mL/kg/mm Hg to 3.79 ± 1.30 mL/kg/mm Hg, P = .017) and decreased total pulmonary resistance, leading to significantly reduced CVP (11.7 ± 2.4 mm Hg to 9.7 ± 2.2 mm Hg, P < .001) and increased cardiac index (CI) (3.09 ± 1.01 L/min/m2 to 3.54 ± 1.19 L/min/m2, P = .047). Furthermore, this strategy significantly reduced the elevations in CVP (19.6 ± 5.3 mm Hg to 15.4 ± 2.7 mm Hg, P = .002) with preserved CI in response to exercise. CVP at rest and during exercise was significantly positively correlated with serum markers of hepatic congestion and fibrosis, respectively.ConclusionsThe super-Fontan strategy is a therapy that turns the heart failure condition of Fontan circulation into a more physiological condition. However, whether the strategy improves long-term prognosis warrants further studies.
| S-EPMC9510926 | biostudies-literature
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: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.
| S-EPMC10891202 | biostudies-literature
Project description:BackgroundNonpulsatile pulmonary blood flow in Fontan circulation results in pulmonary vascular disease, but the potential relationships between pulmonary vascular resistance index (PVRI) and Fontan failure have not been studied. The objective was to determine whether the absence of subpulmonary ventricle in the Fontan circulation would make patients more vulnerable to even low-level elevations in PVRI, and when coupled with low cardiac index, this would identify patients at increased risk of Fontan failure.Methods and resultsTwo hundred sixty-one adult Fontan patients underwent cardiac catheterization; age 26±3 years, men 146 (56%), atriopulmonary Fontan 144 (55%). Patients were divided into 2 groups: those with high PVRI (>2 WU·m2) and low cardiac index <2.5 L min-1 m-2 (group 1, n=70, 30%), and those with normal PVRI and normal cardiac index (group 2, n=182, 70%). Fontan failure was defined by the composite of all-cause mortality, listing for heart transplantation, or initiation of palliative care. There were 68 (26%) cases of Fontan failure during a mean follow-up of 8.6±2.4 years. When compared with group 2, freedom from Fontan failure was significantly lower in group 1: 66% versus 89% at 5 years. The combination of high PVRI and low cardiac index was an independent risk factor for Fontan failure (hazard ratio, 1.84; 95% confidence interval, 1.09-2.85).ConclusionsWhen coupled with low cardiac index, even mild elevations in PVRI identify patients at high risk of Fontan failure. This suggests that pulmonary vascular disease is a key mechanism underlying Fontan failure and supports further studies to understand the pathophysiology and target treatments to pulmonary vascular tone in this population.
| S-EPMC5739063 | biostudies-literature
Project description:Background: Vascular abnormalities, including venous congestion (VC) and pulmonary embolism (PE), have been recognized as frequent COVID-19 imaging patterns and proposed as severity markers. However, the underlying pathophysiological mechanisms remain unclear. In this study, we aimed to characterize the relationship between VC, PE distribution, and alveolar opacities (AO). Methods: This multicenter observational registry (clinicaltrials.gov identifier NCT04824313) included 268 patients diagnosed with SARS-CoV-2 infection and subjected to contrast-enhanced CT between March and June 2020. Acute PE was diagnosed in 61 (22.8%) patients, including 17 females (27.9%), at a mean age of 61.7 ± 14.2 years. Demographic, laboratory, and outcome data were retrieved. We analyzed CT images at the segmental level regarding VC (qualitatively and quantitatively [diameter]), AO (semi-quantitatively as absent, <50%, or >50% involvement), clot location, and distribution related to VC and AO. Segments with vs. without PE were compared. Results: Out of 411 emboli, 82 (20%) were lobar or more proximal and 329 (80%) were segmental or subsegmental. Venous diameters were significantly higher in segments with AO (p = 0.031), unlike arteries (p = 0.138). At the segmental level, 77% of emboli were associated with VC. Overall, PE occurred in 28.2% of segments with AO vs. 21.8% without (p = 0.047). In the absence of VC, however, AO did not affect PE rates (p = 0.94). Conclusions: Vascular changes predominantly affected veins, and most PEs were located in segments with VC. In the absence of VC, AOs were not associated with the PE rate. VC might result from increased flow supported by the hypothesis of pulmonary arteriovenous anastomosis dysregulation as a relevant contributing factor.
| S-EPMC9219696 | biostudies-literature
Project description:BackgroundVascular congestion of the renal medulla-trapped red blood cells in the medullary microvasculature-is a hallmark finding at autopsy in patients with ischemic acute tubular necrosis. Despite this, the pathogenesis of vascular congestion is not well defined.MethodsIn this study, to investigate the pathogenesis of vascular congestion and its role in promoting renal injury, we assessed renal vascular congestion and tubular injury after ischemia reperfusion in rats pretreated with low-dose LPS or saline (control). We used laser Doppler flowmetry to determine whether pretreatment with low-dose LPS prevented vascular congestion by altering renal hemodynamics during reperfusion.ResultsWe found that vascular congestion originated during the ischemic period in the renal venous circulation. In control animals, the return of blood flow was followed by the development of congestion in the capillary plexus of the outer medulla and severe tubular injury early in reperfusion. Laser Doppler flowmetry indicated that blood flow returned rapidly to the medulla, several minutes before recovery of full cortical perfusion. In contrast, LPS pretreatment prevented both the formation of medullary congestion and its associated tubular injury. Laser Doppler flowmetry in LPS-pretreated rats suggested that limiting early reperfusion of the medulla facilitated this protective effect, because it allowed cortical perfusion to recover and clear congestion from the large cortical veins, which also drain the medulla.ConclusionsBlockage of the renal venous vessels and a mismatch in the timing of cortical and medullary reperfusion results in congestion of the outer medulla's capillary plexus and promotes early tubular injury after renal ischemia. These findings indicate that hemodynamics during reperfusion contribute to the renal medulla's susceptibility to ischemic injury.
| S-EPMC8970460 | biostudies-literature
Project description:Subjects with functionally univentricular circulation who have completed staged single ventricle palliation, with the final stage culminating in the Fontan procedure, are often living into adulthood. However, high morbidity and mortality remain prevalent in these patients, as diastolic and systolic dysfunction of the single systemic ventricle are linked to Fontan circulatory failure. We presently investigated the effects of probenecid in post-Fontan patients. Used for decades for the treatment of gout, probenecid has been shown in recent years to positively influence cardiac function via effects on the Transient Receptor Potential Vanilloid 2 (TRPV2) channel in cardiomyocytes. Indeed, we observed that probenecid improved cardiac function and exercise performance in patients with a functionally univentricular circulation. This was consistent with our findings from a retrospective cohort of patients with single ventricle physiology where TRPV2 expression was increased. Experiments in isolated cardiomyocytes associated these positive actions to augmentation of diastolic calcium homeostasis.
| S-EPMC7704717 | biostudies-literature
Project description:BackgroundVenous excess ultrasound (VExUS) is a novel ultrasound technique previously reported as a noninvasive measure of venous congestion and predictor of cardiorenal acute kidney injury.Research questionAre there associations between VExUS grade and cardiac pressures measured by right heart catheterization (RHC) and cardiac biomarkers and clinical outcomes in patients undergoing RHC?Study design and methodsWe conducted a prospective cohort study at the Denver Health Medical Center from December 20, 2022, to March 25, 2023. All patients undergoing RHC underwent a blinded VExUS assessment prior to their procedure. Multivariable regressions were conducted to assess relationships between VExUS grade and cardiac pressures, biomarkers, and changes in weight among patients with heart failure, a proxy for diuretic success. Receiver operating characteristic curve and area under the curve (AUC) were derived for VExUS, inferior vena cava (IVC) diameter, and IVC collapsibility index (ICI) to predict right atrial pressure (RAP) > 10 and < 7 mm Hg.ResultsAmong 81 patients, 45 of whom were inpatients, after adjusting for age, sex, and Charlson Comorbidity Index, there were significant relationships between VexUS grade of 2 (β = 4.8; 95% CI, 2.6-7.1; P < .01) and 3 (β = 11; 95% CI, 8.9-14; P < .01) and RAP, VExUS grade of 2 (β = 6.8; 95% CI, 0.16-13; P = .045) and 3 (β = 15; 95% CI, 7.3-22; P < .01) and mean pulmonary artery pressure, and VExUS grade of 2 (β = 7.0; 95% CI, 3.9-10; P < .01) and 3 (β = 13; 95% CI, 9.5-17; P < .01) and pulmonary capillary wedge pressure. AUC values for VExUS, IVC diameter, and ICI as predictors of RAP > 10 mm Hg were 0.9 (95% CI, 0.83-0.97), 0.77 (95% CI, 0.68-0.88), and 0.65 (95% CI, 0.52-0.78), respectively. AUC values for VExUS, IVC diameter, and ICI as predictors of RAP < 7 mm Hg were 0.79 (95% CI, 0.70-0.87), 0.74 (95% CI, 0.64-0.84), and 0.62 (95% CI, 0.49-0.76), respectively. In a subset of 23 patients with heart failure undergoing diuresis, there was a significant association between VExUS grade 3 and change in weight between time of RHC and discharge (P = .025).InterpretationAlthough more research is required, VExUS has the potential to increase diagnostic and therapeutic capabilities of physicians at the bedside and increase our understanding of the underappreciated problem of venous congestion.
| S-EPMC11317813 | biostudies-literature