Elevated Venous Pressure Research Articles

Right-Sided Heart Failure and Cor Pulmonale in the Pediatric Patient.

Right-Sided Heart Failure and Cor Pulmonale in the Pediatric Patient.

Experimental Hemodynamics Within the Penn State Fontan Circulatory Assist Device.

For children born with a single functional ventricle, the Fontan operation bypasses the right ventricle by forming a four-way total cavopulmonary connection and adapts the existing ventricle for the systemic circulation. However, upon reaching adulthood, many Fontan patients exhibit low cardiac output and elevated venous pressure, eventually requiring a heart transplantation. Despite efforts in developing a new device or using an existing device for failing Fontan support, there is still no Food and Drug Administration-approved device for subpulmonary support. Penn State University is developing a hydrodynamically levitated Fontan circulatory assist device (FCAD) for bridge-to-transplant or destination therapy. The hemodynamics within the FCAD, at both steady and patient averaged pulsatile conditions for three physiological pump operating conditions, were quantified using particle image velocimetry (PIV) to determine the velocity magnitudes and Reynolds normal and shear stresses within the device. Data were acquired at three planes (0 mm and ±25% of the radius) for the inferior and superior vena cavae inlets and the pulmonary artery outlet. The inlets had a blunt velocity profile that became skewed toward the collecting volute as fluid approached the rotor. At the outlet, regardless of the flow condition, a high-velocity jet exited the volute and moved downstream in a helical pattern. Turbulent stresses observed at the volute exit were influenced by the rotor's rotation. Regardless of inlet conditions, the pump demonstrated advantageous behavior for clinical use with a predictable flow field and a low risk of platelet adhesion and hemolysis based on calculated wall shear rates and turbulent stresses, respectively.

Mechanical support for the failing single ventricle after Fontan

Mechanical support for the failing single ventricle after Fontan

Endoscopic third ventriculostomy in an infant with vein of Galen aneurysmal malformation treated by endovascular occlusion: Case report and a review of literature

IntroductionVein of Galen aneurysmal malformations (VGAMs) can, through multiple mechanisms, complicate with hydrocephalus (HCP). It is generally agreed that management strategies in this scenario should focus on endovascular embolizations. Treatment options for non-responders, however, have been only scarcely reported upon. Case presentationWe present a nine-month-old boy with a mural type VGAM complicated by HCP. Despite endovascular occlusion of the sole feeder, the child exhibited hydrocephalus progression prompting an Endoscopic Third Ventriculostomy (ETV). This procedure restored a cerebrospinal fluid (CSF) circulation otherwise impaired by aqueduct obstruction. Later, a new feeder arose and a second embolization was ultimately needed in order to achieve VGAM regression. Throughout four years of follow up, the child attained all developmental marks. Discussion/conclusionVGAMs are prone to hydrocephalus development as there is both an underlying venous congestion and a mechanical, obstructive component. Although there is a rationale for addressing both components, the underlying AV shunts and subsequent venous pressure elevations usually determine failure of traditional CSF shunting strategies. It is therefore challenging to manage HCP in patients who failed to improve following endovascular embolizations. For such cases, ETV stands as an elegant minimal invasive alternative with potential to provide a more physiologic drainage route and thus better allow for neurological development.

Cerebral venous congestion exacerbates cerebral microhemorrhages in mice.

Cerebral microhemorrhages (CMHs; microbleeds), which are small focal intracerebral hemorrhages, importantly contribute to the pathogenesis of cognitive decline and dementia in older adults. Although recently it has been increasingly recognized that the venous side of the cerebral circulation likely plays a fundamental role in the pathogenesis of a wide spectrum of cerebrovascular and brain disorders, its role in the pathogenesis of CMHs has never been studied. The present study was designed to experimentally test the hypothesis that venous congestion can exacerbate the genesis of CMHs. Increased cerebral venous pressure was induced by internal and external jugular vein ligation (JVL) in C57BL/6 mice in which systemic hypertension was induced by treatment with angiotensin II plus L-NAME. Histological analysis (diaminobenzidine staining) showed that mice with JVL developed multiple CMHs. CMHs in mice with JVL were often localized adjacent to veins and venules and their morphology was consistent with venous origin of the bleeds. In brains of mice with JVL, a higher total count of CMHs was observed compared to control mice. CMHs were distributed widely in the brain of mice with JVL, including the cortical gray matter, brain stem, the basal ganglia, subcortical white matter, cerebellum, and the hippocampi. In mice with JVL, there were more CMHs predominantly in cerebral cortex, brain stem, and cerebellum than in control mice. CMH burden, defined as total CMH volume, also significantly increased in mice with JVL. Thus, cerebral venous congestion can exacerbate CMHs. These observations have relevance to the pathogenesis of cognitive impairment associated with right heart failure as well as elevated cerebral venous pressure due to jugular venous reflux in older adults.

Suprachoroidal hemorrhage postintracameral bevacizumab injection: An unusual case report and review of literature

Suprachoroidal hemorrhage (SCH) is a dreaded complication of intraocular surgery. We report a case of a 65-year-old male with left eye primary angle-closure glaucoma and idiopathic elevated episcleral venous pressure with neovascularization of the iris. Due to uncontrolled intraocular pressure even after maximum medical therapy, trabeculectomy with mitomycin C was planned. Preoperative intracameral bevacizumab was given to avoid intraoperative bleeding. Postinjection, localized SCH was noted, which settled spontaneously on conservative management. A combination of ocular and systemic risk factors, such as arteriosclerosis and idiopathic elevated episcleral venous pressure accentuated by intraoperative hypotony during intracameral injection, led to SCH. There are no previous reports of a localized SCH following intracameral bevacizumab.

Ascitic Fluid Analysis Leading to the Diagnosis of Constrictive Pericarditis in 2 Patients.

Although well documented, constrictive pericarditis is a rare entity and an uncommon cause of heart failure. A stiff and noncompliant pericardium creates the disease’s unique hemodynamics and leads to elevated venous pressures, hepatic sinusoidal congestion, and draining of protein-rich fluid into the peritoneal cavity presenting as ascites. The low incidence in addition to its varied and subtle clinical presentations can often lead to a delay in diagnosis. Here, we present 2 clinical cases of constrictive pericarditis in which ascitic fluid analysis was important—one patient who presented with new-onset ascites with concern for cirrhosis and another patient who presented with symptoms concerning for heart failure with ascites. Through their hospital course and workup, we highlight the importance of diagnostic sampling of ascitic fluid to prompt the consideration of constrictive pericarditis followed by utilizing advanced diagnostics, such as echocardiogram and cardiac catheterization to reach the correct diagnosis in an otherwise often overlooked pathology.

The Effects of Vitamin Supplementation Containing L-Methylfolate (Ocufolin® forte) on Retinal Venous Pressure and Homocysteine Plasma Levels in Patients with Glaucoma

# Purpose To report our observations of the effects of Ocufolin® forte on elevated retinal venous pressure (RVP) and elevated serum homocysteine (Hcy) in patients with glaucoma and/or ocular vascular diseases. # Methods A total of 26 patients with glaucoma and/or ocular vascular diseases in at least one eye, abnormal steady-state pattern electroretinography, RVP measured using an ophthalmodynamometer at least 15 mmHg higher than intra-ocular pressure (IOP), fasting serum Hcy level >12 µmol/l and stable and well-controlled IOP (with or without IOP-lowering treatment) received supplementation with Ocufolin® forte for 3 months. # Results As additional treatment was needed in 2 patients their results were excluded from analysis. In the remaining 24 patients, 42 eyes of 21 patients qualified for RVP analysis. Mean IOP remained stable (p=0.15) during the study, but mean RVP dropped by 8.8 mmHg (p<0.001), from 28.1±11.7 mmHg at pre-supplementation to 19.3±7.4 mmHg at 3 months. In 22 of the 24 patients, serum Hcy was analyzed again between 3 days and almost 41 weeks after cessation of supplementation. Serum Hcy levels dropped from 15.8±2.8 µmol/l before to 12.51±2.90 µmol/l after supplementation (p<0.001). # Conclusions In this pilot study, Ocufolin® forte had a clinically relevant and statistically significant RVP lowering effect and led to a clinically relevant and statistically significant Hcy decrease, offering a new treatment modality for eye diseases with increased RVP, such as glaucoma.

Vascular access management of hemodialysis patients at the bedside using point-of-care ultrasound.

When vascular access (VA) for hemodialysis is established using an autologous fistula or synthetic graft, repeated damage from needle insertion at each dialysis session can lead to thrombosis, resulting in vascular stenosis or occlusion that can cause poor blood removal, elevated venous pressure, and other impairments of blood flow. Compact, high-performance ultrasound devices have been developed in recent years. Such devices are used for point-of-care ultrasound (POCUS), which has been used on many occasions for emergency evaluation in the dialysis room and is becoming an important tool in VA management. POCUS provides a wealth of imaging information, such as needle position, whether the needle is inside or outside the blood vessel, and lesion position, width, and depth. This allows clinicians to detect VA problems early and take suitable measures, such as changing the cannulation site, thereby avoiding the need for unnecessary and highly invasive angiography or surgical procedures.

Abstract 14324: Low Pulmonary Venous Flow Drives Cpc-PH Development in a Pulmonary Venous Banding Swine Model of Cpc-PH

Introduction: Combined pre- and post-capillary pulmonary hypertension (Cpc-PH) is the most severe form of PH-LHF. While the impact of elevated left atrial and consequently elevated pulmonary venous (PV) pressure on Cpc-PH progression is well studied, little is known about how compromised PV flow secondary to LHF affects disease progression. To assess the hypothesis that decreased PV flow induces Cpc-PH, we developed a large animal model of Cpc-PH by decreasing PV flow independent of LHF. Methods: Survival pulmonary venous banding (PVB) surgery was performed on a large white male pig (9kg), which was then followed for 16 weeks. A pig of the same sex and weight underwent a sham operation as control. Both animals underwent cardiac 4D flow MRI and right heart catheterization (RHC) in a terminal study. Results: At 16 weeks post-surgery, MR imaging demonstrated that PVB decreased mean flow and peak velocity in the right (RIPV) and left inferior pulmonary veins (LIPV) and MPA (figure and table). PVB also decreased MPA relative area change (RAC) (table). RHC demonstrated elevated PCWP, mPAP, PVR, and decreased RV EF (table). Also, Fulton index was increased demonstrating RV hypertrophy (table). Discussion: In conclusion, this study utilized PVB to demonstrate the ability of decreased PV flow to drive Cpc-PH development in the absence of LHF. Our preliminary data suggest a low flow state in the lung can increase RV afterload and induce RV dysfunction. Further studies with a larger sample size are needed to confirm this pathomechanical mechanism. Figure. MRI image of PV confluence narrowing from the PVB. Insert shows flow rates from RIPV and LIPV (blue), across PVB (red), and into LA (green).

Acute Kidney Injury and Renal Replacement Therapy After Fontan Operation

Fontan circulation leads to chronic elevation of central venous pressure. We sought to identify the incidence, risk factors, and survival among patients who developed acute kidney injury (AKI) after the Fontan operation. We retrospectively reviewed 1,166 patients who had Fontan operation/revision at Mayo Clinic Rochester from 1973 to 2017 and identified patients who had AKI (defined by AKI Network criteria) within 7days of surgery. A total of 132 patients (11%) developed AKI after the Fontan operation with no significant era effect. Of those who developed AKI, severe (grade 3) kidney injury was present in 101 patients (76.5%). Multivariable risk factors for AKI were asplenia (odds ratio [OR] 4.2, p <0.0001), elevated preoperative pulmonary artery pressure (per 1 mm Hg increase, OR 1.04, p=0.0002), intraoperative arrhythmias (OR 1.9, p=0.02), and elevated post-bypass Fontan pressure (per 1 mm Hg increase, OR 1.12, p=0.0007). Renal replacement therapy (RRT) was used in 72 patients (54%), predominantly through peritoneal dialysis (n=56, 78%). Multivariable risk factors for RRT were age ≤3years (OR 9.7, p=0.0004), female gender (OR 2.6, p=0.02), and aortic cross-clamp time >60minutes (OR 3.1, p=0.01). Patients with AKI had more postoperative complications, including bleeding, stroke, pericardial tamponade, low cardiac output state and cardiac arrest, than those without AKI. This resulted in longer intensive care unit stay (39 vs 17days, p=0.0001). In-hospital mortality was exceedingly higher among patients with AKI versus no AKI (58%, 76 of 132 vs 10%, 99 of 1,034, p <0.0001); however, there was no significant difference based on the need for RRT. Recovery from AKI was observed in 56 patients (42%). Over 20-year follow-up, patients with AKI had a distinctly higher all-cause-mortality (82%) than those without AKI (35%). It is prudent to identity patients at a higher risk of developing postoperative AKI after Fontan operation to ensure renal protective strategies in the perioperative period. Postoperative AKI leads to substantial short and long-term morbidity and mortality, but the need for RRT does not affect the outcomes.

The role of venous pressure variability during hemodialysis in the prediction of impending arteriovenous graft occlusion.

Elevated venous pressure during hemodialysis (VPHD) is associated with arteriovenous graft (AVG) stenosis. This study investigated the role of VPHD variations in the prediction of impending AVG occlusion. Data were retrieved from 118 operations to treat AVG occlusion (occlusion group) and 149 operations to treat significant AVG stenosis (stenosis group). In addition to analyzing the VPHD values for the three hemodialysis (HD) sessions prior to the intervention, VPHD values were normalized to mean blood pressure (MBP), blood flow rate (BFR), BFR × MBP, and BFR2 × MBP to yield ratios for analysis. The coefficient of variation (CV) was used to measure relative variations. The within-group comparisons for both groups revealed no significant differences in the VPHD mean and CV values among the three HD sessions prior to intervention. However, the CVs for VPHD/MBP, VPHD/(BFR × MBP), and VPHD/(BFR2 × MBP) exhibited significant elevation in the occlusion group during the last HD session prior to intervention compared with both the penultimate and antepenultimate within-group HD data (p < 0.05). In the receiver operating characteristic curve analysis, the CV for VPHD/(BFR2 × MBP) was the only parameter able to discriminate between the last and the penultimate HD outcomes (p < 0.001). According to a multivariate analysis, after controlling for covariates, CV for VPHD/(BFR2 × MBP) >8.76% was associated with a higher risk of AVG thrombosis (odds ratio: 3.17, p < 0.001). Increasing the variation in VPHD/(BFR2 × MBP) may increase the probability of AVG occlusion.

Systemic Venous Hypertension and Low Output Are Prevalent at Catheterization in Adults with Pulmonary Atresia and Intact Ventricular Septum Regardless of Repair Strategy

Patients with pulmonary atresia and intact ventricular septum (PA-IVS) require intervention early in life, and most survive to a definitive procedure of either Fontan circulation or right ventricle to pulmonary artery (RV-PA) repair. It remains unknown how surgical strategy impacts hemodynamics and comorbidities in adults. Retrospective analysis of adults (age ≥18 years) with PA-IVS undergoing hemodynamic catheterization at Mayo Clinic, MN between January 2000 through January 2020 was performed. 14 patients in the RV-PA group (71% biventricular, 29% 1.5 ventricle repair) and 19 post-Fontan patients [9 lateral tunnel (48%), 6 atriopulmonary (32%), and 4 extracardiac (21%)] were identified. Median age was 29 (21, 34) years. There were no differences in demographics and laboratory data (including MELD-XI) between groups. All patients assessed for liver disease had evidence of hepatic congestion or cirrhosis (14 in the Fontan group and 4 in the RV-PA group). Invasive hemodynamics were comparable between groups with the Fontan and RV-PA groups having similar systemic venous pressure (15.7±4.4 vs. 14.3±6.2, p = .44) and cardiac output (2.2±0.6 vs. 2.0±0.4 L/min/m2, p = .23). There was no difference in transplant-free survival (p = .92; 5-year transplant-free survival RV-PA 84%, Fontan 80%). Hemodynamic derangements, namely elevated systemic venous pressure and low cardiac output, are prevalent in patients with PA-IVS undergoing cardiac catheterization regardless of surgical strategy.

S3682 Management of Right-Sided Carcinoid Heart Failure

Introduction: Carcinoid heart disease is a rare disease affecting around 20% of patients with carcinoid syndrome. It is considered a result of high circulating serotonin levels depositing into heart valves. The characterized symptoms of carcinoid syndrome are vasomotor flushing, gastrointestinal hypermotility and cardiac involvement. Right heart valve disorders increase morbidity and mortality due to right heart failure complications of fluid overload. This case presents a 48 year old woman with new findings on echocardiogram compatible with right heart failure. Case Description/Methods: A 48 year old woman with a past medical history of hypothyroidism presented with shortness of breath for the last month. No productive cough, no sick contacts, no fevers or chills. Endorses diffuse redness on her face and right arm. Antistreptolysin A returned positive and completed a 10 day course of cephalexin without relief. Other related symptoms were abdominal distress, nonbloody diarrhea and tachycardia. She lost approximately 30 pounds in the last 2 months due to chronic diarrhea. Recent celiac serology testing has been negative. CT Abdomen and Pelvis with contrast shows a prominent, speculated nodal mass at the root of the mesentery with focal nodular thickening of the duodenal wall. 5-HIAA returned at 40mg/24h (Reference < 30 mg/24hr). Echocardiogram revealed grade 1 diastolic dysfunction, preserved ejection fraction and moderate tricuspid regurgitation. Lasix was started for diuresis along with octreotide to calm down the systemic 5-HIAA surge. She will be followed up outpatient for surgical evaluation. Discussion: Carcinoid heart disease is caused by the deposition of pearly fibrotic plaques into the endocardium of right sided valves leading to multiple patterns of severe valve dysfunction. Plaque formation causes leaflet thickening, and fusion of the valves. Echocardiography remains a reliable method for the definitive diagnosis. Valve replacement is currently the gold standard treatment for symptomatic carcinoid valve disease. However, debates remain in terms of the choice of heart valve prosthesis. The surgical indications of carcinoid heart disease are symptomatic right ventricular failure, severe valvular dysfunction and systemic venous pressure elevation. Contraindications are end-stage metastatic disease poorly controlled carcinoid symptoms despite octreotide therapy medical management. This case highlights the rare syndrome of carcinoid heart disease with follow up surgery in the outpatient..

Does the venous pressure theory of multiple sclerosis pathophysiology deserve a second chance?

The theory that multiple sclerosis is related to venous pressure has been discredited due to previous operator dependent diagnostic criteria and premature attempts at treatment. (1) An elevation in venous pressure may only be a component of the compliance changes found in MS. (2) The neck veins may only supply a component of the venous pressure elevation found intracranially. Although a more targeted approach towards neck angioplasty (both towards disease subtype and those with more favorable stenoses) may be beneficial, we would advocate caution. We encourage others to give the venous pressure theory a second chance and to replicate our work.

Superior sagittal sinus dural arteriovenous fistula caused by treatment of meningioma masquerades as sinus thrombosis

Dural arteriovenous fistulas (DAVF) are rare acquired lesions resulting from abnormal shunting between intracranial dural arteries and venous system. Typically arising from structural weakness of the dura and a coinciding trigger factor, DAVFs can present with similar clinical and imaging characteristics to sinus thrombosis. A 61-year-old male with a history of meningioma previously managed with subtotal resection and stereotactic radiosurgery presented with progressive right-sided vision loss and bilateral papilledema. Initial imaging suggested possible sinus occlusion. Catheter angiogram revealed a Borden-Shucart grade III DAVF of the superior sagittal sinus and elevated venous pressures and the patient subsequently underwent endovascular transarterial intervention twice. We report on the first case of a superior sagittal sinus DAVF occurring after surgical resection of a parasagittal meningioma.

Intraocular Pressure and Glaucoma in Thyroid Eye Disease.

Current literature lacks a summary of knowledge on intraocular pressure (IOP) elevation and glaucoma in thyroid eye disease (TED). This review aims to augment existing literature by providing such a summary. It qualitatively evaluates current knowledge on the pathogenesis, prevalence, and management of concomitant ocular hypertension or glaucoma in TED patients. In this narrative review, relevant publications were identified through a computerized database search. Search results were screened for relevance. Correspondence, Editorials, and Letters to the Editors were excluded. References cited within the identified articles were used to further augment the search. Information extracted for qualitative analysis included epidemiologic data, methods of IOP assessment, management protocols, and response to treatment. Studies in current literature are relatively heterogenous, differing in country of origin, TED cohort sizes, and IOP measurement techniques. Further studies are required to elucidate the true epidemiologic relationship between TED and ocular hypertension or glaucoma. Proposed models of IOP elevation include elevation of episcleral venous pressure, mucopolysaccharide deposition within the trabecular meshwork, restrictive myopathy, steroid-induced glaucoma, and secondary glaucoma. IOP-reducing effects of TED treatment options are discussed. While raised IOP in TED is a common phenomenon, the diagnosis of glaucoma in TED requires a high index of suspicion before any intervention.

Assessment of Phenobarbital Administration to Reduce Opioid and Benzodiazepine Use in the Immediate Postoperative Period Following Stage 2 Single-Ventricle Palliation

OBJECTIVE The Glenn procedure may lead to the development of elevated cerebral venous pressures, which is believed to result in “Glenn headaches.” This manifests as excessive irritability, often requiring significant use of opioids and benzodiazepines. This study was designed to report our experience with the use of phenobarbital in the postoperative phase after the Glenn procedure. METHODS We performed a retrospective chart review to compare Glenn patients before and after implementation of a sedation protocol using phenobarbital. The 2 groups were compared for demographics, surgical characteristics, and cumulative sedation usage. Correlation coefficients between the preoperative catheterization variables and sedation usage were also calculated. RESULTS Groups A (pre-phenobarbital; n = 8) and B (post-phenobarbital; n = 11) were comparable in terms of demographics, cardiac anatomy, preoperative catheterization data, and hemodynamics. Patients in Group B received a median dose of 21.8 mg/kg of phenobarbital during their ICU stay. Although there was a decreased administration of morphine equivalents (2.60 mg/kg vs 2.25 mg/kg, p = 0.38), benzodiazepine (0.1 mg/kg vs 0.074 mg/kg, p = 0.43), and dexmedetomidine (47 mcg/kg vs 37.2 mcg/kg, p = 0.53) in Group B, the differences were not statistically significant. There was also no strong correlation between preoperative hemodynamic variables and the postoperative sedation requirement, and there was no statistically significant difference in overall outcomes between the 2 groups. CONCLUSIONS While phenobarbital may have mitigated the use of opioids, benzodiazepines, and alpha-agonist agents in some postoperative Glenn patients, the overall findings for all patients were not statistically significant. Further prospective studies are needed to ascertain the role of phenobarbital in these patients.

Possible Markers of Venous Sinus Pressure Elevation in Multiple Sclerosis: Correlations with Gender and Disease Progression

In a previous study, multiple sclerosis (MS) was found to be associated with an increase in intracranial arterial pulsation volume and a reduction in venous sinus compliance, affecting pulsation dampening. There was a suggestion that the reduction in compliance of the sagittal sinus in MS was caused by an increase in venous pressure, secondary to transverse sinus stenosis. Some differences were noted depending on the gender of the patients, however, the original study was relatively underpowered for further sub-classification. The purpose of the current study is to enroll a larger number of patients to allow sub-classification on gender and disease type to further evaluate the markers of possible venous pressure alteration. 103 patients with MS were prospectively recruited from an MS clinic and compared to 50 matched non-MS patients. Using 3DT1 post contrast images, the sagittal sinus cross-sectional area was measured. The narrowest portion of the transverse sinuses was located and the cross sectional areas and wetted circumferences were measured to calculate the minimum hydraulic and effective diameters. The jugular bulb heights were measured. Voxel wise brain morphometry was performed to evaluate atrophy. Statistical analysis was performed using non-parametric methods and was assessed using α≤0.05. Compared to controls, the MS patients' sagittal sinuses were 23% larger in cross-section (p<0.0001), the transverse sinuses had an average effective stenosis of 39% by area (p<0.0001) and there was a 62% increase in jugular bulb height (p=0.0001). The MS patients showed a reduction in normalized grey matter volume of 2.8% (p= 0.0001). Males with MS showed worse outcomes compared to females, with an increased EDSS and grey matter loss and had a 23% larger sagittal sinus area (p=0.02), 22% higher jugular bulb height (p=0.03) but a lower transverse sinus stenosis percentage (19% vs 48%, p<0.0001). Progressive forms of MS also had worse outcomes and had a 19% larger sagittal sinus area (p=0.04) compared to relapsing remitting MS. In this larger cohort, worse outcomes in both males and progressive forms of MS were associated with larger sagittal sinuses. The possible cause of the altered sinus pressure in females was narrower transverse sinuses. In males, higher jugular bulbs may be associated with increased venous sinus pressure.

Obesity, venous capacitance, and venous compliance in heart failure with preserved ejection fraction.

Circulating blood volume is functionally divided between the unstressed volume, which fills the vascular space, and stressed blood volume (SBV), which generates vascular wall tension and intravascular pressure. With decreases in venous capacitance, blood functionally shifts to the SBV, increasing central venous pressure and pulmonary venous pressures. Obesity is associated with both elevated venous pressure and heart failure with preserved ejection fraction (HFpEF). To explore the mechanisms underlying this association, we evaluated relationships between blood volume distribution, venous compliance, and body mass in patients with and without HFpEF. Subjects with HFpEF (n= 62) and non-cardiac dyspnoea (NCD) (n= 79) underwent invasive haemodynamic exercise testing with echocardiography. SBV was estimated (eSBV) from measured haemodynamic variables fit to a comprehensive cardiovascular model. Compared to NCD, patients with HFpEF displayed a leftward-shifted central venous pressure-dimension relationship, indicating reduced venous compliance. eSBV was 81% higher at rest and 69% higher during exercise in HFpEF than NCD (both P< 0.0001), indicating reduced venous capacitance. Despite greater augmented eSBV with exercise, the increase in cardiac output was reduced in HFpEF, suggesting operation on the plateau of the Starling curve. Exercise eSBV was directly correlated with higher body mass index (r=0.77, P< 0.0001) and inversely correlated with right ventricular-pulmonary arterial coupling (r=-0.57, all P< 0.0001). Patients with HFpEF display reductions in systemic venous compliance and increased eSBV related to reduced venous capacitance, abnormalities in right ventricular-pulmonary artery interaction, and increased body fat. These data provide new evidence supporting an important role of venous dysfunction in obesity-related HFpEF and suggest that therapies that improve venous function may hold promise to improve clinical status in this cohort.