Pressure Gradient Measurement Research Articles

Non-invasive assessment of left ventricular hemodynamic forces in hypertrophic cardiomyopathy

Abstract Background Hemodynamic force (HDF) analysis allows non-invasive measurement of intraventricular pressure gradients, portraying cyclic spatial-temporal interaction between blood and tissues. Impaired HDFs have been implicated in early detecting of adverse cardiac remodelling and treatment response in various cardiovascular disorders, providing insights into cardiac physiology not offered by traditional cardiovascular imaging (1). Mainly explored in heart failure, HDF analysis has not been previously applied to hypertrophic cardiomyopathy (HCM). Purpose To investigate differences in systo-diastolic function in HCM patients compared to healthy controls using HDF analysis. Methods Forty patients with HCM diagnosis (20 obstructive and 20 non-obstructive) were retrospectively evaluated in comparison with 22 healthy controls. Left ventricular (LV) HDFs were derived from routine transthoracic apical 4-, 2- and 3-chamber views using a dedicated software. Apical-basal HDF curves were generated, where positive deflections represent forces directed from the LV apex to the base, whilst negative ones are directed toward the apex. Amplitude and timing parameters were derived, the latter indexed to total cardiac cycle duration. Results Table 1 shows the demographic, clinical and echocardiographic characteristics of HCM compared to controls. Patients with HCM were older, had a slower heart rate due to treatment with beta-blockers, and showed hypercontractility, as expressed by higher LV ejection fraction. Compared to controls, HCM patients showed reduced LV longitudinal force, i.e. the force during the whole cardiac cycle (4.17% [2.36-5.52] vs. 6.01% [4.73-7.78], p=0.002), shorter time interval to systolic peak (0.15 [0.12-0.16] vs. 0.19 [0.17-0.20], p <0.001), and shorter duration of LV impulse (0.29 [0.27-0.32] vs. 0.34 [0.32-0.37], p <0.001) (Figure 1). However, no differences in terms of systolic force peak (p=0.283) or LV impulse intensity (p=0.689) were detected. During the transition between systole and diastole, LV suction (i.e. the interval including late systolic deceleration and early diastolic suction) was significantly longer (0.26 [0.22-0.29] vs. 0.23 [0.21-0.25], p=0.023) but less pronounced (6.30% [4.56-8.44] vs. 8.72% [6.71-12.59], p=0.005), likely reflecting a relaxation impairment from the very beginning of diastole. Such impairment was maintained during early diastolic filling, where the amplitude of the positive deceleration flow force was severely reduced in HCM compared to controls (2.98% [1.98-4.58] vs. 7.11% [4.55-8.72], p <0.001). Conclusions HDF analysis in HCM patients revealed unique systolic and diastolic changes reflecting faster LV contraction during systole and slower and weaker LV forces during diastole. This analysis deepens our understanding of HCM mechanic abnormalities and may help assess response to innovative treatment options.

Endo-hepatology: Why should we do endoscopic ultrasound-guided interventions to the liver that we could do through the skin?

Endoscopic ultrasound (EUS)-guided interventions on the liver such as diffuse biopsy and portal pressure gradient measurement are emerging as potential alternatives to percutaneous procedures. The purpose of this editorial was to address all the indications that could potentially make an EUS-guided approach a possible alternative to the percutaneous procedures with respect to the proce-dures that could join the EUS examination such as upper endoscopy for gastro-esophageal varices, pancreaticobiliary investigation with EUS, and other potential advantages in terms of patient safety. The issue of a holistic gastroenterologist approach was also discussed along with the potential for developing clinical research.

The independent prognostic value of perioperative hepatic venous pressure gradient measurements in patients with portal hypertension who underwent laparoscopic splenectomy plus esophagogastric devascularization

BackgroundHepatic venous pressure gradient (HVPG) is considered the gold standard for diagnosing portal hypertension (PHT). Laparoscopic splenectomy plus esophagogastric devascularization (LSED) is an important surgery for treating PHT. However, the variation trend of HVPG after surgery is not clear. Moreover, whether HVPG can provide precise prognostic information for patients undergoing surgery remains to be further studied. This study aimed to investigate the independent prognostic value of HVPG in LSED.MethodsFrom January 2016 to March 2023, 135 patients with PHT underwent LSED at our hospital were retrospectively evaluated. We analyzed the correlations between clinical indicators and history of upper gastrointestinal bleeding (UGIB). Among them, 57 patients remeasured postoperative HVPG. We further investigated the postoperative alterations of HVPG and correlative factors, as well as the relationship between the HVPG and postoperative UGIB.ResultsIn this study, we found that 94 patients with preoperative UGIB (16.27 ± 5.73 mmHg) had a higher baseline HVPG than the other 41 patients without (14.02 ± 5.90 mmHg) (p = 0.04). The mean postoperative HVPG significantly decreased (-3.57 ± 8.09 mmHg, p = 0.001) compared to the baseline, and 66% of patients (38/57) experienced a decreased HVPG-response after surgery. The baseline HVPG and preoperative CTP class B were associated with the decreased HVPG-response (p<0.05). Additionally, patients with postoperative HVPG decreased>20% from baseline exhibited better recurrent hemorrhage-free survival rates than those without (log-rank, p = 0.013).ConclusionWe found that LSED led to a significantly decreased HVPG, and patients with postoperative HVPG decreased >20% obtained better UGIB-free survival benefits than those without.

Endoscopic ultrasound-guided vascular interventions: A review (with videos).

Endoscopic ultrasound (EUS) has evolved from a diagnostic to an interventional modality, allowing precise vascular access and therapy. EUS-guided vascular access of the portal vein has received increasing attention in recent years as a diagnostic and therapeutic tool. EUS-guided portal pressure gradient directly measures the hepatic vein portal pressure gradient and is crucial for understanding of liver function and prognostication of liver disease. EUS facilitates the sampling of portal venous blood to obtain circulating tumor cells (CTCs) in pancreatobiliary malignancies. This technique aids in the diagnosis and staging of cancers. EUS-guided interventions have a substantial potential for diagnosing portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma. EUS-guided coil and glue embolization have higher efficacy for the treatment of gastric varices than direct endoscopic glue. Pseudoaneurysm (PsA), a rare vascular complication of acute and chronic pancreatitis, is typically managed with interventional radiology (IR)-guided embolization and surgery. EUS is increasingly used in specialized centers for non-variceal gastrointestinal bleeding, particularly for pseudoaneurysm-related bleeding. There is limited data on EUS-guided intervention for bleeding ectopic varices, rectal varices and Dieulafoy lesions, but it is becoming more widely accepted. In this extensive review, we evaluated both current and potential future applications of EUS-guided vascular interventions, including EUS-guided gastric variceal bleed therapy, rectal and ectopic varices, pseudoaneurysmal bleeding, splenic artery embolization, portal pressure gradient measurement, portal vein sampling for CTCs, fine needle aspiration of PVTT, intrahepatic portosystemic shunt placement, liver tumor ablation and EUS-guided cardiac intervention.

Agreement of echocardiographic and catheterization-based methods of transpulmonary pressure gradient measurement in dogs

Introduction/ObjectivesDoppler echocardiographic estimation of transpulmonary pressure gradient (PG) is widely used to determine severity of pulmonary valve stenosis and indication for transcatheter intervention. The objective of this study was to describe agreement between Doppler echocardiographic methods of transpulmonary PG estimation and direct peak-to-peak pressure gradient at catheterization (PGcath) in dogs. We hypothesized that with reference to PGcath, mean echocardiographic PG (PGecho-mean) would have less bias than peak modal instantaneous echocardiographic PG (PGecho-peak). AnimalsClient-owned dogs with congenital pulmonary valve stenosis that underwent balloon pulmonary valvuloplasty at one of two veterinary teaching hospitals between June 2012 and May 2022 were included in this study. Materials and MethodsCases that underwent transthoracic echocardiography and subsequent balloon pulmonary valvuloplasty separated by 30 or fewer days were retrospectively identified. For each echocardiogram, average PGecho-mean (mmHg) and average PGecho-peak (mmHg) were calculated from stored spectral Doppler recordings. Peak right ventricular-to-peak pulmonary artery PG data (mmHg) were obtained from catheterization reports. Bland–Altman analysis was used to assess agreement between echocardiographic and catheterization data. ResultsData from 209 dogs (n = 215 instances) were evaluated. Proportional bias, greater at higher gradients, was observed for PGecho-mean versus PGcath (P<0.001). A constant bias of −38.12 mmHg was observed for PGecho-peak versus PGcath (P=0.62). Bias for both echocardiographic variables had wide limits of agreement that increased with PG. ConclusionsPGecho-mean and PGecho-peak underestimated and overestimated PGcath, respectively, preventing their interchangeability with PGcath.

Analysis of cerebral venous sinus stenosis by flat panel angiographic CT (FP-CT) to guide treatment for idiopathic intracranial hypertension.

Cerebral venous sinus stenting (CVSS) is an effective treatment for idiopathic intracranial hypertension (IIH) secondary to dural venous sinus stenosis. Traditional selection of patients for CVSS has been made by microcatheter manometry, but pressure measurements are often equivocal. Here we present the results of a series of cases in which venous flat-panel CT (FP-CT) was used as an adjunct to microcatheter manometry to improve decision making and precise stent placement during CVSS. Ten consecutive patients with IIH underwent angiography with microcatheter manometry and venous FP-CT, with CVSS if indicated by the results. Cross-sectional measurements of the narrowed sinus were obtained on FP-CT before and after stenting. After the procedure, clinical outcomes were tracked. Follow-up with quantitative MRA with sinus flow measurements was also performed, when available. There was an exponential correlation between measured pressure gradient and degree of stenosis calculated using venous FP-CT. All patients with both a high degree of stenosis measured by FP-CT and a high pressure gradient across the stenosis showed a clinical benefit from stenting. True measurement of the cross-sectional area of the dural sinus, made by venous phase FP-CT, has a high degree of correlation with elevated venous pressure gradient across the point of stenosis. Even in a limited series of cases, we found an exponential decrease in flow with increasing severity of stenosis. Furthermore, patients with both an elevated venous pressure gradient and critical stenosis of the sinus on FP-CT showed symptomatic improvement after stenting.

Aetiology-specific inflammation patterns in patients and rat models of compensated cirrhosis

BackgroundCirrhosis is associated with a proinflammatory environment. AimsTo analyse aetiology-specific inflammation patterns in compensated cirrhosis in animal models and patients. MethodsPortal pressure (PP), fibrosis (collagen proportionate area [CPA]) and hepatic inflammation were measured in cirrhotic rat models (thioacetamide [TAA;n = 12]; choline-deficient high-fat diet [CDHFD;n = 12]; bile duct ligation [BDL;n = 16]). Compensated cirrhotic patients (alcohol-related liver disease [ALD;n = 67]; metabolic dysfunction-associated steatohepatitis [MASH;n = 50]; cholestatic liver disease [primary biliary cholangitis [PBC]/primary sclerosing cholangitis [PSC];n = 22]) undergoing hepatic venous pressure gradient (HVPG) measurement were included. ResultsIn rats, hepatic proinflammatory gene expression was highest in CDHFD and lowest in TAA, despite comparable PP levels. Across all animal models, Tnfa/Il6 correlated positively with CPA, and Mcp1 with elevated PP. Mcp1 was also associated with increased CPA in TAA/CDHFD. Mcp1/Cxcl1 showed a model-independent positive correlation to transaminases. Il1b correlated positively with CPA/PP in BDL and with transaminases in CDHFD. In patients, CRP/IL-6 were lower in MASH compared to ALD or PBC/PSC, regardless of hepatic function. IgA/IgG were highest and complement factors lowest in ALD. More pronounced systemic inflammation was linked to higher HVPG primarily in ALD/MASH. ConclusionProinflammatory pathways are upregulated across all liver disease aetiologies, yet their association with fibrosis and portal hypertension can vary.

EUS-Guided Vascular Interventions: Recent Advances.

Endoscopic ultrasound (EUS)-guided vascular interventions were first reported in 2000 in a study that evaluated the utility of EUS in sclerotherapy of esophageal varices. Currently, gastric variceal therapy and portosystemic pressure gradient (PPG) measurements are the most widely utilized applications. Ectopic variceal obliteration, splenic artery embolization, aneurysm/pseudoaneurysm treatment, portal venous sampling, and portosystemic shunt creation using EUS are some of the other emerging interventions. Since the release of the American Gastroenterological Association (AGA)'s commentary in 2023, which primarily endorses EUS-guided gastric variceal therapy and EUS-PPG measurement, several new studies have been published supporting the use of EUS for various vascular conditions. In this review, we present the recent advances in this field, critically appraising new studies and trials.

Advanced cystic fibrosis liver disease: Endovascular, endoscopic, radiologic, and surgical considerations.

Up to 90% of people with CF (pwCF) will have some form of hepatobiliary involvement. This manuscript aims to explore the different endovascular, endoscopic, radiological and surgical procedures available to diagnose and manage the most severe form of CF hepatobiliary involvement (CFHBI) known as advanced cystic fibrosis liver disease (aCFLD),seen in 10% of pwCF. These procedures and interventions include liver biopsy, hepatic venous pressure gradient measurement, gastrostomy tube placement to optimize nutrition, paracentesis, endoscopic variceal control of bleeding and portosystemic shunting before liver transplantation. By utilizing advanced diagnostic or surgical techniques, healthcare professionals of pwCF can more effectively manage patients with CFHBI and aCFLD and potentially improve patient outcomes.

Identifying the optimal measurement timing and hemodynamic targets of portal pressure gradient after TIPS in patients with cirrhosis and variceal bleeding

The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p= 0.002) and OHE (0.40, 95% CI 0.17-0.91, p= 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14mmHg that was associated with a decreased risk of OHE and effective prevention of PHC. PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14mmHg is associated with reduced encephalopathy but not compromised clinical efficacy. The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. ClinicalTrials.gov, ID: NCT03590288.

Prevalence and prognostic value of zinc and selenium deficiency in advanced chronic liver disease.

Zinc and selenium are essential trace elements involved in important (patho)physiological processes. The prevalence and prognostic implications of zinc and selenium deficiency in patients with advanced chronic liver disease (ACLD) remain unknown. We determined serum zinc and selenium concentrations in 309 patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement between 2019 and 2022. We evaluated the prevalence of zinc/selenium deficiency and assessed its association with severity of ACLD and liver-related events (LRE, i.e. first/further hepatic decompensation/liver-related death). Among 309 ACLD patients (median: age: 57 [IQR: 50-64], MELD: 11 [IQR: 9-16], HVPG: 17 [IQR: 11-20]), 73% (227) and 63% (195) were deficient in zinc and selenium, respectively. Decompensated (dACLD) patients showed significantly lower serum zinc (median: 48 [IQR: 38-59] vs. compensated, cACLD: 65 [IQR: 54-78], p < 0.001) and selenium levels (median: 4.9 [IQR 4.0-6.2] vs. cACLD: 6.1 [IQR 5.1-7.3], p < 0.001). Significant correlations of zinc/selenium levels were found with MELD (zinc: ρ = -0.498, p < 0.001; selenium: ρ = -0.295, p < 0.001), HVPG (zinc: ρ = -0.400, p < 0.001; selenium: ρ = -0.157, p = 0.006) and liver disease-driving mechanisms (IL6, bile-acid homeostasis). On multivariable analysis, low zinc/selenium levels, age and MELD remained independently associated with LRE. Zinc and selenium deficiencies are common in ACLD patients especially with higher MELD and HVPG. Low zinc and selenium levels independently predicted hepatic decompensation and liver-related death. The effect of zinc/selenium supplementation in ACLD should be investigated in future trials.

The Balloon Catheter Method and the End-hole Catheter Method in the Measurement of Hepatic Venous Pressure Gradient: a Comparative Study.

This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients. From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed. The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%). HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method.

Quantification of anatomical aortic valve area by multi-detector computed tomography: A pilot 3D-morphological modeling of the stenotic aortic valve

BackgroundAortic-valve-stenosis (AS) is a frequent degenerative valvular-disease and carries dismal outcome under-medical-treatment. Transvalvular pressure gradient reflects severity of the valve-disease but is highly dependent on flow-conditions and on other valvular/aortic characteristics. Alternatively, aortic-valve-area (AVA) represents a measure of aortic-valve lesion severity conceptually essential and practically widely-recognized but exhibits multiple-limitations. MethodsWe analyzed the 4D multi-detector computed tomography(MDCT) of 20 randomly selected patients with severe AS. For each-patient, we generated the 3D-model of the valve and of its calcifications, and we computed the anatomical AVA accounting for the 3D-morphology of the leaflets in three-different-ways. Finally, we compared our results vs. Doppler-based AVAE measurements and vs. 2D-planimetric AVA-measurements. Results3D-reconstruction and identification of the cusps were successful in 90% of the cases. The calcification patterns where highly-variable over patients, ranging from multiple small deposits to wide and c-shaped deposits running from commissure-to-commissure.AVAE was 82 ± 15 mm2. When segmenting 18 image planes, AVATight, AVAProj-Ann, AVAProj-Tip and their average AVAAve were equal to 80 ± 16, 88 ± 20, 93 ± 21 and 87 ± 19 mm2, respectively, while AVAPlan was equal to 143 ± 50 mm2. Linear-regression of the three measurements vs. AVAE yielded regression slopes equal to 1.26, 1.13 and 0.93 for AVAProj-Ann, AVAProj-Tip and AVATight, respectively. The respective Pearson-coefficients were 0.85,0.86 and 0.90. Conversely, when comparing AVAPlan vs. AVAE, linear regression yielded a slope of 1.73 and a Pearson coefficient of 0.53. ConclusionsWe described a new-method to obtain a set of flow-independent quantifications that complement pressure gradient measurements and combine the advantages of previously proposed methods, while bypassing the corresponding-limitations.

Mitral valve repair with leaflet resection versus preservation for degenerative posterior leaflet prolapse

ObjectivesThe optimal technique for repairing posterior mitral valve leaflet prolapse remains undetermined. We aimed to compare leaflet resection and neochordae implantation in patients undergoing mitral valve repair for posterior leaflet prolapse, focusing on transmitral pressure gradient and recurrence of mitral regurgitation. MethodsWe enrolled patients undergoing mitral valve repair using either leaflet resection or neochordae implantation for single-segment prolapse of posterior mitral valve leaflet between 2000 and 2021 at our institution. Longitudinal outcomes were evaluated after adjustments with inverse-probability-of-treatment weighting. Repeat echocardiographic measurements (n = 3473, 5.4/patient) of transmitral pressure gradient and significant (moderate or severe) mitral regurgitation recurrence were estimated using nonlinear mixed-effect models. Subgroup analyses were conducted based on the size and type of prosthesis. ResultsAmong 639 patients, leaflet resection was used in 479 (75.0%) and neochordae implantation was used in 160 (25.0%). In the inverse-probability-of-treatment weighting adjusted cohort, the risk of death (P = .623) and mitral valve reoperation (P = .340) did not significantly differ between the 2 groups during a median follow-up of 97.3 months. Echocardiographic data showed comparable mean (at 5 years, 3.8 vs 4.0 mm Hg; P = .442) and peak (9.6 vs 10.4 mm Hg; P = .131) pressure gradients between groups, which persisted in most subgroup analyses. However, neochordae implantation was associated with a higher probability of significant mitral regurgitation recurrence compared with leaflet resection (at 5 years, 16.1% vs 7.0%; P < .001). ConclusionsLeaflet resection yielded similar clinical outcomes and transmitral pressure gradients compared with neochordae implantation after mitral valve repair, with a lower mitral regurgitation recurrence rate. These findings underscore the need to reassess the efficacy of neochordae implantation relative to leaflet resection.

Metabolomics reveals altered metabolites in cirrhotic patients with severe portal hypertension in Tibetan population.

Portal hypertension (PHT) presents a challenging issue of liver cirrhosis. This study aims to identify novel biomarkers for severe PHT (SPHT) and explore the pathophysiological mechanisms underlying PHT progression. Twenty-three Tibetan cirrhotic patients who underwent hepatic venous pressure gradient (HVPG) measurement were included. Eleven patients had an HVPG between 5 mmHg and 15 mmHg (MPHT), while 12 had an HVPG ≥16 mmHg (SPHT). Peripheral sera were analyzed using liquid chromatograph-mass spectrometer for metabolomic assessment. An additional 14 patients were recruited for validation of metabolites. Seven hundred forty-five metabolites were detected and significant differences in metabolomics between MPHT and SPHT patients were observed. Employing a threshold of p < 0.05 and a variable importance in projection score >1, 153 differential metabolites were identified. A significant number of these metabolites were lipids and lipid-like molecules. Pisumionoside and N-decanoylglycine (N-DG) exhibited the highest area under the curve (AUC) values (0.947 and 0.9091, respectively). Additional differential metabolites with AUC >0.8 included 6-(4-ethyl-2-methoxyphenoxy)-3,4,5-trihydroxyoxane-2-carboxylic acid, sphinganine 1-phosphate, 4-hydroxytriazolam, 4,5-dihydroorotic acid, 6-hydroxy-1H-indole-3-acetamide, 7alpha-(thiomethyl)spironolactone, 6-deoxohomodolichosterone, glutaminylisoleucine, taurocholic acid 3-sulfate, and Phe Ser. Enzyme-linked immunosorbent assay further confirmed elevated levels of sphinganine 1-phosphate, N-DG, and serotonin in SPHT patients. Significant disruptions in linoleic acid, amino acid, sphingolipid metabolisms, and the citrate cycle were observed in SPHT patients. Pisumionoside and N-DG are identified as promising biomarkers for SPHT. The progression of PHT may be associated with disturbances in lipid, linoleic acid, and amino acid metabolisms, as well as alterations in the citrate cycle.

Histologic Findings of Sinusoidal Dilatation and Congestion in Liver Grafts Do Not Correlate with Hepatic Venous Anastomotic Gradients.

Hepatic venous transplant anastomotic pressure gradient measurement and transjugular liver biopsy are commonly used in clinical decision-making in patients with suspected anastomotic hepatic venous outflow obstruction. This investigation aimed to determine if sinusoidal dilatation and congestion on histology are predictive of hepatic venous anastomotic outflow obstruction, and if it can help select patients for hepatic vein anastomosis stenting. This is a single-center retrospective study of 166 transjugular liver biopsies in 139 patients obtained concurrently with transplant venous anastomotic pressure gradient measurement. Demographic characteristics, laboratory parameters, procedure and clinical data, and histology of time-zero allograft biopsies were analyzed. No relationship was found between transplant venous anastomotic pressure gradient and sinusoidal dilatation and congestion (P = 0.92). Logistic regression analysis for sinusoidal dilatation and congestion confirmed a significant relationship with reperfusion/preservation injury and/or necrosis of the allograft at time-zero biopsy (OR 6.6 [1.3-33.1], P = 0.02). There is no relationship between histologic sinusoidal dilatation and congestion and liver transplant hepatic vein anastomotic gradient. In this study group, sinusoidal dilatation and congestion is a nonspecific histopathologic finding that is not a reliable criterion to select patients for venous anastomosis stenting.

Moderate aortic stenosis: Navigating the uncharted.

Aortic stenosis (AS) stands as the most common valvular heart disease in developed countries and is characterized by progressive narrowing of the aortic valve orifice resulting in elevated transvalvular flow resistance, left ventricular hypertrophy, and progressive increased risk of heart failure and sudden death. This narrative review explores clinical challenges and evolving perspectives in moderate AS, where discrepancies between aortic valve area and pressure gradient measurements may pose diagnostic and therapeutic quandaries. Transthoracic echocardiography is the first-line imaging modality for AS evaluation, yet cases of discordance may require the application of ancillary noninvasive diagnostic modalities. This review underscores the importance of accurate grading of AS severity, especially in low-gradient phenotypes, emphasizing the need for vigilant follow-up. Current clinical guidelines primarily recommend aortic valve replacement for severe AS, potentially overlooking latent risks in moderate disease stages. The noninvasive multimodality imaging approach-including echocardiography, cardiac magnetic resonance, computed tomography, and nuclear techniques-provides unique insights into adaptive and maladaptive cardiac remodeling in AS and offers a promising avenue to deliver precise indications and exact timing for intervention in moderate AS phenotypes and asymptomatic patients, potentially improving long-term outcomes. Nevertheless, what we may have gleaned from a large amount of observational data is still insufficient to build a robust framework for clinical decision-making in moderate AS. Future research will prioritize randomized clinical trials designed to weigh the benefits and risks of preemptive aortic valve replacement in the management of moderate AS, as directed by specific imaging and nonimaging biomarkers.

Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here, we investigate the prognostic value of HVPG in MASLD-related compensated ACLD (MASLD-cACLD). This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with diabetes) were included. Clinically significant portal hypertension (CSPH: i.e., HVPG ≥10mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in those with MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio [SHR] 5.13; p <0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (adjusted SHR per mmHg: 1.20, p <0.001). HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both. While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD patients, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in patients with MASLD-cACLD without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Measurement of pressure gradients near the interface in the viscous fingering instability

The viscous fingering instability, which forms when a less-viscous fluid invades a more-viscous one within a confined geometry, is an iconic system for studying pattern formation. For both miscible and immiscible fluid pairs the growth dynamics change after the initial instability onset and the global structures, typical of late-time growth, are governed by the viscosity ratio. Here we introduce an experimental technique to measure flow throughout the inner and outer fluids. This probes the existence of a new length scale associated with the local pressure gradients around the interface and allows us to compare our results to the predictions of a previously proposed model for late-time finger growth. Published by the American Physical Society 2024

Predicting response to non-selective beta-blockers with liver-spleen stiffness and heart rate in patients with liver cirrhosis and high-risk varices.

Non-selective beta-blockers (NSBB) are used for primary prophylaxis in patients with liver cirrhosis and high-risk varices (HRVs). Assessing therapeutic response is challenging due to the invasive nature of hepatic venous pressure gradient (HVPG) measurement. This study aims to define anoninvasive machine-learning basedapproach to determine response to NSBB in patients with liver cirrhosis and HRVs. We conducted a prospective study on a cohort of cirrhotic patients with documented HRVs receiving NSBB treatment. Patients were followed-up with clinical and elastography appointments at 3, 6, and 12months after NSBB treatment initiation. NSBB response was defined as stationary or downstaging variceal grading at the 12-month esophagogastroduodenoscopy (EGD). In contrast, non-response was defined as upstaging variceal grading at the 12-month EGD or at least one variceal hemorrhage episode during the 12-month follow-up. We chose cut-off values for univariate and multivariate model with 100% specificity. According to least absolute shrinkage and selection operator (LASSO) regression, spleen stiffness (SS) and liver stiffness (LS) percentual decrease, along with changes in heart rate (HR) at 3months were the most significant predictors of NSBB response. A decrease > 11.5% in SS, > 16.8% in LS, and > 25.3% in HR was associated with better prediction of clinical response to NSBB. SS percentual decrease showed the highest accuracy (86.4%) with high sensitivity (78.8%) when compared to LS and HR. The multivariate model incorporating SS, LS, and HR showed the highest discrimination and calibration metrics (AUROC = 0.96), with the optimal cut-off of 0.90 (sensitivity 94.2%, specificity 100%, PPV 95.7%, NPV 100%, accuracy 97.5%).