Fontan Circulation and Aortic Stiffness: Insights into Vascular Dynamics and Haemodynamic Interplay.

Increased aortic stiffness predisposes cardiac afterload and influences cardiac function. Congenital heart diseases involving aortic arch malformation and extended cardiovascular surgery, i.e. univentricular heart diseases, can lead to increased aortic stiffness. This study aimed to investigate whether Fontan patients (FO) have increased aortic stiffness within distinct aortic segments, and whether these parameters relate to Fontan-specific haemodynamics. In a prospective case-control study, 20 FO and 49 heart-transplanted control subjects with biventricular circulation underwent invasive cardiac catheterisation. We invasively measured pulse wave velocity (PWV) in the ascending aorta and along the entire aorta. Haemodynamic parameters, including end-diastolic pressure, pulmonary artery pressure, the cardiac index and systemic vascular resistance index were also assessed. FO exhibited significantly higher ascending aorta PWV (aPWV) than controls (FO: 7.2 ± 2.4 m/s|Controls: 4.9 ± 0.7 m/s, p < 0.001) and compared to the inner group central aorta PWV (cPWV; FO: 5.5 ± 1.2 m/s|Controls: 5.3 ± 1.0 m/s). Multivariate analysis confirmed this aPWV elevation in FO even after adjusting for age and BMI. aPWV and cPWV were almost identical within the control group. Correlation analyses revealed associations between cPWV and blood pressure in controls, while correlations were less apparent in FO. We detected no significant association between the aPWV and other haemodynamic parameters in any of our groups. FO exhibit increased aPWV, indicating specific vascular stiffness in the ascending aorta, while their overall aortic stiffness remains comparable to controls. Further research is needed to understand the implications of these findings on Fontan circulation and long-term cardiovascular health. CENTRAL MESSAGE: Fontan patients show increased aortic arch pulse wave velocity, suggesting specific vascular stiffness. PERSPECTIVE STATEMENT: Our study offers rare insights into pulse wave velocity in Fontan patients, highlighting increased arterial stiffness in the aortic arch. Vascular stiffness was particularly increased in the area of surgical reconstruction. This indicates the need for further research on vascular stiffness in Fontan circulation to understand its impact on cardiovascular health. CLINICAL TRIAL REGISTRATION: German clinical trial registration, DRKS00015066.

AnXplore: a comprehensive fluid-structure interaction study of 101 intracranial aneurysms.

Advances in computational fluid dynamics continuously extend the comprehension of aneurysm growth and rupture, intending to assist physicians in devising effective treatment strategies. While most studies have first modelled intracranial aneurysm walls as fully rigid with a focus on understanding blood flow characteristics, some researchers further introduced Fluid-Structure Interaction (FSI) and reported notable haemodynamic alterations for a few aneurysm cases when considering wall compliance. In this work, we explore further this research direction by studying 101 intracranial sidewall aneurysms, emphasizing the differences between rigid and deformable-wall simulations. The proposed dataset along with simulation parameters are shared for the sake of reproducibility. A wide range of haemodynamic patterns has been statistically analyzed with a particular focus on the impact of the wall modelling choice. Notable deviations in flow characteristics and commonly employed risk indicators are reported, particularly with near-dome blood recirculations being significantly impacted by the pulsating dynamics of the walls. This leads to substantial fluctuations in the sac-averaged oscillatory shear index, ranging from -36% to +674% of the standard rigid-wall value. Going a step further, haemodynamics obtained when simulating a flow-diverter stent modelled in conjunction with FSI are showcased for the first time, revealing a 73% increase in systolic sac-average velocity for the compliant-wall setting compared to its rigid counterpart. This last finding demonstrates the decisive impact that FSI modelling can have in predicting treatment outcomes.

Chronic inflammation with microglia senescence at basal forebrain: impact on cholinergic deficit in Alzheimer's brain haemodynamics.

Cholinergic innervation in the brain is involved in modulating neurovascular function including cerebral blood flow haemodynamics in response to neuronal activity. Cholinergic deficit is associated with pathophysiology in Alzheimer's disease, albeit the aetiology remains to be clarified. In the current study, neocortex cerebral blood flow response to acetylcholine was evaluated by Laser-Doppler Flowmetry (LDF) in 3xTgAD Alzheimer's disease model) and wild-type mice of two age groups. The peak of cerebral blood flow to acetylcholine (i.v.) from baseline levels (% ΔrCBF) was higher in young 3xTgAD versus in wild-type mice (48.35; 95% CI:27.03-69.67 versus 22.70; CI:15.5-29.91, P < 0.05); this was reversed in old 3xTgAD mice (21.44; CI:2.52-40.35 versus 23.25; CI:23.25-39). Choline acetyltransferase protein was reduced in neocortex, while cerebrovascular reactivity to acetylcholine was preserved in young 3×TgAD mice. This suggests endogenous acetylcholine deficit and possible cholinergic denervation from selected cholinergic nuclei within the basal forebrain. The early deposition of tauopathy moieties (mutant hTau and pTau181) and its coincidence in cholinergic cell clusters (occasionaly), were observed at the basal forebrain of 3xTgAD mice including substantia innominate, nucleus Basalis of Meynert and nucleus of horizontal limb diagonal band of Broca. A prominent feature was microglia interacting tauopathy and demonstrated a variety of morphology changes particularly when located in proximity to tauopathy. The microglia ramified phenotype was reduced as evaluated by the ramification index and Fractal analysis. Increased microglia senescence, identified as SASP (senescence-associated secretory phenotype), was colocalization with p16Ink4ɑ, a marker of irreversible cell-cycle arrest in old 3xTgAD versus wild-type mice (P = 0.001). The p16Ink4ɑ was also observed in neuronal cells bearing tauopathy within the basal forebrain of 3xTgAD mice. TNF-ɑ, the pro-inflammatory cytokine elevated persistently in microglia (Pearson's correlation coefficient = 0.62) and the loss of cholinergic cells in vulnerable basal forebrain environment, was indicated by image analysis in 3xTgAD mice, which linked to the cholinergic deficits in neocortex rCBF haemodynamics. Our study revealed the early change of CBF haemodynamics to acetylcholine in 3xTgAD model. As a major effector of brain innate immune activation, microglia SASP with age-related disease progression is indicative of immune cell senescence, which contributes to chronic inflammation and cholinergic deficits at the basal forebrain. Targeting neuroinflammation and senescence may mitigate cholinergic pathophysiology in Alzheimer's disease.

Cardiac power output ratio: Novel survival predictor after percutaneous ventricular assist device in cardiogenic shock.

AIMS: Currently, there is limited data on prognostic indicators after insertion of percutaneous ventricular assist device (PVAD) in the treatment of cardiogenic shock (CS). This study evaluated the prognostic role of cardiac power output (CPO) ratio, defined as CPO at 24 h divided by early CPO (30 min to 2 h), in CS patients after PVAD. METHODS AND RESULTS: Consecutive CS patients from the QEH-PVAD Registry were followed up for survival at 90 days after PVAD. Among 121 consecutive patients, 98 underwent right heart catheterization after PVAD, with CPO ratio available in 68 patients. The CPO ratio and 24-h CPO, but not the early CPO post PVAD, were significantly associated with 90-day survival, with corresponding area under curve in ROC analysis of 0.816, 0.740, and 0.469, respectively. In multivariate analysis, only the CPO ratio and lactate level at 24 h remained as independent survival predictors. The CPO ratio was not associated with age, sex, and body size. Patients with lower CPO ratio had significantly lower coronary perfusion pressure, worse right heart indices, and higher pulmonary vascular resistance. A lower CPO ratio was also significantly associated with mechanical ventilation and higher creatine kinase levels in myocardial infarction patients. CONCLUSION: In post-PVAD patients, the CPO ratio outperformed the absolute CPO values and other haemodynamic metrics in predicting survival at 90 days. Such a proportional change of CPO over time, likely reflecting native heart function recovery, may help to guide management of CS patients post-PVAD.

Intubation of critically ill patients: A pilot study of minute-by-minute physiological changes within an Australian tertiary intensive care unit.

BACKGROUND: There are no published minute-by-minute physiological assessment data for endotracheal intubation (ETT) performed in the intensive care unit (ICU). The majority of physiological data is available from Europe and North America where etomidate is the induction agent administered most commonly. AIMS: The aim of this study was to describe the feasibility of obtaining minute-by-minute physiological and medication data surrounding ETT in an Australian tertiary ICU and to assess its associated outcomes. METHODS: We performed a single-centre feasibility observational study. We obtained minute-by-minute data on physiological variables and medications for 15 min before and 30 min after ETT. We assessed feasibility as enrolled to screened patient ratio and completeness of data collection in enrolled patients. Severe hypotension (systolic blood pressure < 65 mmHg) and severe hypoxaemia (pulse oximetry saturation < 80%) were the secondary clinical outcomes. RESULTS: We screened 43 patients and studied 30 patients. The median age was 58.5 (interquartile range: 49-70) years, and 18 (60%) were male. Near-complete (97%) physiological and medication data were obtained in all patients at all times. Overall, 15 (50%) ETTs occurred after hours (17:30-08:00) and 90% were by video laryngoscopy with a 90% first-pass success rate. Prophylactic vasopressors were used in 50% of ETTs. Fentanyl was used in all except one ETT at a median dose of 2.5 mcg/kg. Propofol (63%) or midazolam (50%) were used as adjuncts at low dose. Rocuronium was used in all but one patient. There were no episodes of severe hypotension and only one episode of short-lived severe hypoxaemia. CONCLUSION: Minute-by-minute recording of ETT-associated physiological changes in the ICU was feasible but only fully available in two-thirds of the screened patients. ETT was based on fentanyl induction, low-dose adjunctive sedation, and frequent prophylactic vasopressor therapy and was associated with no severe hypotension and a single short-lived episode of severe hypoxaemia.

Haemodynamic contributors to pulmonary hypertension across the spectrum of adult congenital heart disease.

AIMS: Adult congenital heart disease (ACHD) includes multiple disease states that predispose to pulmonary hypertension (PH). Haemodynamically, PH depends on abnormalities in three components: pulmonary blood flow (Qp), pulmonary vascular resistance (PVR) and pulmonary venous pressure (PVP). We sought to evaluate the prevalence and prognostic impact of individual haemodynamic abnormalities in ACHD. METHODS AND RESULTS: Retrospective study of ACHD patients undergoing cardiac catheterization at Mayo Clinic between 1999 and 2022 who were followed for the combined endpoint of death/heart transplantation. Among 1005 patients, 37% had mean pulmonary artery pressure (mPAP) ≥25 mmHg with more systemic ventricular disease, cyanotic disease and shunt lesions, highest N-terminal pro-B-type natriuretic peptide and worse right heart remodelling/dysfunction. Among those with biventricular circulation, elevated PVP, PVR and mPAP were associated with prognosis, but not increased Qp >8 L/min. However, risk of death/transplant increased for PVR only at ≥3 Wood units (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.17-4.15; p < 0.0001) and for mPAP only at ≥25 mmHg (HR 3.15, 95% CI 2.17-4.58; p < 0.0001), not at current recommended lower cutpoints. Combined abnormalities in PVP and PVR were associated with worst outcome (HR 5.20, 95% CI 3.55-7.63; p < 0.0001) with intermediate risk with either abnormality (HR 2.11, 95% CI 1.46-3.04; p < 0.0001). Findings were consistent across type of biventricular ACHD. Only with the Fontan (univentricular) circulation was a lower mPAP threshold (20 mmHg) associated with adverse outcomes. CONCLUSIONS: Elevation of mPAP ≥25 mmHg in ACHD with a biventricular circulation is prognostically important regardless of disease phenotype, but milder PH of 21-25 mmHg is not associated with adverse outcome unless associated with Fontan circulation. Elevation in PVP >15 mmHg and PVR ≥3 Wood units were each individually associated with mortality with combined abnormalities associated with greatest risk. Categorizing PH in ACHD by haemodynamic mechanism (PVR, PVP or Qp) allows meaningful prognostication, and may allow more unified study of targeted therapies across heterogeneous disease states in ACHD.

Comparing the haemodynamic effects of high- and low-dose opioid anaesthesia: a secondary analysis of a randomised controlled trial.

Post-induction hypotension (MAP < 65 mmHg) occurs frequently and is usually caused by the cardiovascular adverse effects of the anaesthetic induction drugs used. We hypothesize that a clinically significant difference in the incidence and severity of hypotension will be found when different doses of propofol and remifentanil are used for induction of anaesthesia. METHODS: This is a secondary analysis of a randomised controlled trial wherein four groups (A-D) of patients received one out of four different combinations of propofol and remifentanil, titrated to a predicted equipotency in probability of tolerance to laryngoscopy (PTOL) according to the Bouillon interaction model. In group A, a high dose of propofol and a low dose of remifentanil was administered, and across the groups this ratio was gradually changed until it was reversed in group D. Mean and systolic arterial blood pressure (MAP, SAP) were compared at four time points (Tbaseline, Tpost-bolus, T3min, Tnadir) within and between groups Heart rate, bispectral index (BIS) and the incidence of hypotension were compared. RESULTS: Data from 76 patients was used. At Tpost-bolus a statistically significant lower MAP and SAP was found in group A versus D (p = 0.011 and p = 0.002). A significant higher heart rate was found at T3min and Tnadir between groups A and B when compared to groups C and D (p = < 0.001 and p = 0.002). A significant difference in BIS value was found over all groups at T3min and Tnadir (both p < 0.001). All other outcomes did not differ significantly between groups. CONCLUSION: Induction of anaesthesia with different predicted equipotent combinations of propofol and remifentanil did result in statistically different but clinically irrelevant differences in haemodynamic endpoints during induction of anaesthesia. Our study could not identify preferable drug combinations that decrease the risk for hypotension after induction, although they all yield a similar predicted PTOL.

Non-invasive fractional flow reserve estimation in coronary arteries using angiographic images.

Coronary artery disease is the leading global cause of mortality and Fractional Flow Reserve (FFR) is widely regarded as the gold standard for assessing coronary artery stenosis severity. However, due to the limitations of invasive FFR measurements, there is a pressing need for a highly accurate virtual FFR calculation framework. Additionally, it's essential to consider local haemodynamic factors such as time-averaged wall shear stress (TAWSS), which play a critical role in advancement of atherosclerosis. This study introduces an innovative FFR computation method that involves creating five patient-specific geometries from two-dimensional coronary angiography images and conducting numerical simulations using computational fluid dynamics with a three-element Windkessel model boundary condition at the outlet to predict haemodynamic distribution. Furthermore, four distinct boundary condition methodologies are applied to each geometry for comprehensive analysis. Several haemodynamic features, including velocity, pressure, TAWSS, and oscillatory shear index are investigated and compared for each case. Results show that models with average boundary conditions can predict FFR values accurately and observed errors between invasive FFR and virtual FFR are found to be less than 5%.

Cardiac function, haemodynamics, and valve competence with exercise in patients with heart failure with preserved ejection fraction and mild to moderate secondary mitral regurgitation.

AIMS: This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure-volume relationships, and reduced LV longitudinal contractile function. CONCLUSIONS: Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

Study on the Effects of Angiotensin Receptor/Neprilysin Inhibitors on Renal Haemodynamics in Healthy Dogs.

An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs.

Static and dynamic analysis of cerebral blood flow in fifty-six large arterial vessel networks.

Objective.The cerebral vasculature is formed of an intricate network of blood vessels over many different length scales. Changes in their structure and connection are implicated in multiple cerebrovascular and neurological disorders. In this study, we present a novel approach to the quantitative analysis of the cerebral macrovasculature using computational and mathematical tools in a large dataset.Approach.We analysed a publicly available vessel dataset from a cohort of 56 (32/24F/M) healthy subjects. This dataset includes digital reconstructions of human brain macrovasculatures. We then propose a new mathematical model to compute blood flow dynamics and pressure distributions within these 56-representative cerebral macrovasculatures and quantify the results across this cohort.Main results.Statistical analysis showed that the steady state level of cerebrovascular resistance (CVR) gradually increases with age in both men and women. These age-related changes in CVR are in good agreement with previously reported values. All subjects were found to have only small phase angles (<6°) between blood pressure and blood flow at the cardiac frequency.Significance.These results showed that the dynamic component of blood flow adds very little phase shift at the cardiac frequency, which implies that the cerebral macrocirculation can be regarded as close to steady state in its behaviour, at least in healthy populations, irrespective of age or sex. This implies that the phase shift observed in measurements of blood flow in cerebral vessels is caused by behaviour further down the vascular bed. This behaviour is important for future statistical models of the dynamic maintenance of oxygen and nutrient supply to the brain.

Assessing pressure wave components for aortic stiffness monitoring through spectral regression learning.

Aims: The ageing process notably induces structural changes in the arterial system, primarily manifesting as increased aortic stiffness, a precursor to cardiovascular events. While wave separation analysis is a robust tool for decomposing the components of blood pressure waveform, its relationship with cardiovascular events, such as aortic stiffening, is incompletely understood. Furthermore, its applicability has been limited due to the need for concurrent measurements of pressure and flow. Our aim in this study addresses this gap by introducing a spectral regression learning method for pressure-only wave separation analysis. Methods and results: Leveraging data from the Framingham Heart Study (2640 individuals, 55% women), we evaluate the accuracy of pressure-only estimates, their interchangeability with a reference method based on ultrasound-derived flow waves, and their association with carotid-femoral pulse wave velocity (PWV). Method-derived estimates are strongly correlated with the reference ones for forward wave amplitude ( R 2 = 0.91 ), backward wave amplitude ( R 2 = 0.88 ), and reflection index ( R 2 = 0.87 ) and moderately correlated with a time delay between forward and backward waves ( R 2 = 0.38 ). The proposed pressure-only method shows interchangeability with the reference method through covariate analysis. Adjusting for age, sex, body size, mean blood pressure, and heart rate, the results suggest that both pressure-only and pressure-flow evaluations of wave separation parameters yield similar model performances for predicting carotid-femoral PWV, with forward wave amplitude being the only significant factor (P < 0.001; 95% confidence interval, 0.056-0.097). Conclusion: We propose an interchangeable pressure-only wave separation analysis method and demonstrate its clinical applicability in capturing aortic stiffening. The proposed method provides a valuable non-invasive tool for assessing cardiovascular health.

Haemodynamic effect of a leg compression bandage on the distal posterior tibial artery using 4D flow magnetic resonance imaging: A quantitative study.

The uncertainty concerning the physiological effects of compression bandaging on the peripheral blood flow is a challenge for healthcare professionals. The main objective was to determine the haemodynamic impact on the distal posterior tibial artery after the application of a high-compression leg multicomponent bandaging system using 4D flow magnetic resonance imaging. Leg dominance disparities of the posterior tibial artery before and after the application of the compressive bandage were also analysed. Twenty-eight healthy female volunteers were recruited (mean: 25.71, standard deviation: 4.74 years old) through a non-probability convenience sampling. The 4D flow magnetic resonance imaging of the distal tibial posterior artery was performed in all participants, first under standard resting conditions and after the application of a compression bandage in the leg. When the strong compressive bandage was applied, the area of the assessed artery decreased by 14.2%, whilst the average speed increased by 19.6% and the flow rate increased by 184.8%. There were differences between the haemodynamic parameters of both legs according to dominance, being statistically significantly lower in the dominant leg. The application of strong compressive bandaging significantly increases the arterial flow and mean velocity in the distal segment of the posterior tibial artery, in healthy volunteers by 4D flow magnetic resonance imaging. In this study, leg dominance influenced some of the haemodynamic parameters. According to the results, leg compression bandages cannot be contraindicated in vascular ulcers with arterial compromise.

Integrating Computational and Biological Hemodynamic Approaches to Improve Modeling of Atherosclerotic Arteries.

Atherosclerosis is the primary cause of cardiovascular disease, resulting in mortality, elevated healthcare costs, diminished productivity, and reduced quality of life for individuals and their communities. This is exacerbated by the limited understanding of its underlying causes and limitations in current therapeutic interventions, highlighting the need for sophisticated models of atherosclerosis. This review critically evaluates the computational and biological models of atherosclerosis, focusing on the study of hemodynamics in atherosclerotic coronary arteries. Computational models account for the geometrical complexities and hemodynamics of the blood vessels and stenoses, but they fail to capture the complex biological processes involved in atherosclerosis. Different in vitro and in vivo biological models can capture aspects of the biological complexity of healthy and stenosed vessels, but rarely mimic the human anatomy and physiological hemodynamics, and require significantly more time, cost, and resources. Therefore, emerging strategies are examined that integrate computational and biological models, and the potential of advances in imaging, biofabrication, and machine learning is explored in developing more effective models of atherosclerosis.

Right ventricular outflow tract diameter change with exercise: a prospective exercise echocardiography and invasive CPET study.

While cardiac output reserve with exercise predicts outcomes in cardiac and pulmonary vascular disease, precise quantification of exercise cardiac output requires invasive cardiopulmonary testing (iCPET). To improve the accuracy of cardiac output reserve estimation with transthoracic echocardiography (TTE), this prospective study aims to define changes in right ventricular outflow tract diameter (RVOTd) with exercise and its relationship with invasively measured haemodynamics. Twenty subjects underwent simultaneous TTE and iCPET, with data collected at rest, leg-raise, 25 W, 50 W (n = 16), 75 W (n = 14), and 100 W (n = 6). This was followed by a second exercise study with real-time RV pressure-volume loops at similar stages (except leg-raise). The overall cohort included heart failure with preserved ejection fraction (n = 12), pulmonary arterial hypertension (n = 5), and non-cardiac dyspnoea (n = 3). RVOTd was reverse engineered from the TTE-derived RVOT velocity time integral (VTI) and iCPET-derived stroke volume, using the formula: Fick stroke volume = RVOT VTI × RVOT area (wherein RVOT area = π × [RVOTd/2]2). RVOTd increased by nearly 3-4% at every 25 W increment. Using linear regression models, where each subject is treated as a categorical variable and adjusting for subject intercept, RVOTd was correlated with haemodynamic variables (cardiac output, heart rate, pulmonary artery and RV pressures). Of all the predictor haemodynamic variables, cardiac output had the highest r2 model fit (adjusted r2 = 0.68), with a unit increase in cardiac output associated with a 0.0678 increase in RVOTd (P < 0.001). Our findings indicate that RVOTd increases by 3-4% with every 25 W increment, predominantly correlated with cardiac output augmentation. These results can improve the accuracy of cardiac output reserve estimation by adjusting for RVOTd with graded exercise during non-invasive CPET and echocardiogram. However, future studies are needed to define these relationships for left ventricular outflow tract diameter.

Novel weaning assessment for veno-arteriovenous to veno-venous extracorporeal membrane oxygenation using pump-controlled retrograde trial off.

INTRODUCTION: Pump-controlled retrograde trial off (PCRTO) is described as an effective weaning strategy for veno-arterial extracorporeal membrane oxygenation (ECMO) in the guidelines. Contrastingly, there is no established weaning strategy for veno-arteriovenous (V-AV) ECMO. We report a novel application of PCRTO in a patient undergoing V-AV ECMO. CASE REPORT: A 49-year-old man had pneumonia and a history of kidney transplantation. Two days after intubation, respiratory failure progressed and veno-venous (V-V) ECMO was introduced. On day 7 after ECMO, the configuration was changed to V-AV ECMO owing to septic cardiomyopathy due to suspected cholangitis. On day 15, with partial haemodynamic improvement and persistent respiratory failure, PCRTO was performed; the patient was safely returned to V-V ECMO. DISCUSSION: In patients undergoing V-AV ECMO, PCRTO could have the potential to accurately simulate decannulation of the arterial cannula. CONCLUSION: This novel weaning strategy could be considered in patients undergoing V-AV ECMO.

Application of 4D flow MRI for exploring factors affecting haemodynamics of iliac veins in asymptomatic population.

BACKGROUND: Haemodynamics plays an important role in the development of vascular disease. There is currently a lack of studies evaluating the characteristics and affecting factors of the iliac vein haemodynamics in clinical practice. OBJECTIVE: The goal of this study was to use 4D flow MRI to explore the haemodynamic characteristics of iliac veins and its affecting factors in an asymptomatic population. METHODS: Thirty consecutive volunteers without venous-related symptoms or signs underwent four-dimensional postprocessing of their MRI images. Relevant parameters, the demographic data, common iliac vein-inferior vena cava angle, iliac vein area, tortuosity, iliac vein mean flow, mean velocity was computed and analysed. T tests and Spearman's tests were used for analysing. A P value of 0.05 or less was considered significant. RESULTS: Height and iliac vein area were positively correlated with flow, while degree of stenosis, and common iliac-inferior vena cava angle were negatively correlated with that. Degree of stenosis was positively correlated with velocity, but the common iliac-inferior vena cava angle and iliac vein tortuosity were negatively correlated with that. The mean flow and velocity of iliac veins in females were lower than males. The mean flow and velocity of the left iliac veins were lower than those of the right. CONCLUSION: The height, gender, tortuosity, degree of stenosis, common iliac vein-inferior vena cava angle of the iliac vein are important factors that affect flow and velocity of the iliac veins. There were differences in haemodynamic parameters of the bilateral iliac veins.

Physiological mechanisms behind respiratory variations in right atrial pressure in pulmonary hypertension.

Impaired respiratory variation of right atrial pressure (RAP) in severe pulmonary hypertension (PH) suggests difficulty tolerating increased preload during inspiration. Our study explores whether this impairment links to specific factors: right ventricular (RV) diastolic function, elevated RV afterload, systolic RV function, or RV-pulmonary arterial (PA) coupling. We retrospectively evaluated respiratory RAP variation in all participants enrolled in the EXERTION study. Impaired respiratory variation was defined as end-expiratory RAP - end-inspiratory RAP ≤ 2 mm Hg. RV function and afterload were evaluated using conductance catheterization. Impaired diastolic RV function was defined as end-diastolic elastance (Eed) ≥ median (0.19 mm Hg/mL). Seventy-five patients were included; PH was diagnosed in 57 patients and invasively excluded in 18 patients. Of the 75 patients, 31 (41%) had impaired RAP variation, which was linked with impaired RV systolic function and RV-PA coupling and increased tricuspid regurgitation and Eed as compared to patients with preserved RAP variation. In backward regression, RAP variation associated only with Eed. RAP variation but not simple RAP identified impaired diastolic RV function (area under the receiver operating characteristic curve [95% confidence interval]: 0.712 [0.592, 0.832] and 0.496 [0.358, 0.634], respectively). During exercise, patients with impaired RAP variation experienced greater RV dilatation and reduced diastolic reserve and cardiac output/index compared with patients with preserved RAP variation. Preserved RAP variation was associated with a better prognosis than impaired RAP variation based on the 2022 European Society of Cardiology/European Respiratory Society risk score (chi-square P = 0.025) and survival free from clinical worsening (91% vs 71% at 1 year and 79% vs 50% at 2 years [log-rank P = 0.020]; hazard ratio: 0.397 [95% confidence interval: 0.178, 0.884]). Subgroup analyses in patients with group 1 and group 4 PH demonstrated consistent findings with those observed in the overall study cohort. Respiratory RAP variations reflect RV diastolic function, are independent of RV-PA coupling or tricuspid regurgitation, are associated with exercise-induced haemodynamic changes, and are prognostic in PH.Trial registration. NCT04663217.

Extracellular vesicles and their effect on vascular haemodynamics: a systematic review.

Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 109-1010 circulating EVs/mL in the plasma of healthy individuals derived from various sources. While the effect of EVs on vascular haemodynamic parameters will be dependent on the details of the model studied, we systematically searched and summarized current literature to find patterns in how exogenously injected EVs affected vascular haemodynamics. Under homoeostatic conditions, evidence from wire and pressure myography data demonstrate that injecting isolated EVs derived from cell types found in blood and blood vessels resulted in the impairment of vasodilation in blood vessels ex vivo. Impaired vasodilation was also observed in rodents receiving intravenous injections of human plasma EVs from cardiovascular diseases including valvular heart disease, acute coronary syndrome, myocardial infarction and end stage renal disease. When EVs were derived from models of metabolic syndromes, such as diabetes, these EVs enhanced vasoconstriction responses in blood vessels ex vivo. There were fewer publications that assessed the effect of EVs in anaesthetised or conscious animals to confirm whether effects on the vasculature observed in ex vivo studies translated into alterations in vascular haemodynamics in vivo. In the available conscious animal studies, the in vivo data did not always align with the ex vivo data. This highlights the importance of in vivo work to determine the effects of EVs on the integrative vascular haemodynamics.

Dynamic cerebral autoregulation is governed by two time constants: Arterial transit time and feedback time constant.

Dynamic cerebral autoregulation (dCA) is the mechanism that describes how the brain maintains cerebral blood flow approximately constant in response to short-term changes in arterial blood pressure. This is known to be impaired in many different pathological conditions, including ischaemic and haemorrhagic stroke, dementia and traumatic brain injury. Many different approaches have thus been used both to analyse and to quantify this mechanism in a range of healthy and diseased subjects, including data-driven models (in both the time and the frequency domain) and biophysical models. However, despite the substantial body of work on both biophysical models and data-driven models of dCA, there remains little work that links the two together. One of the reasons for this is proposed to be the discrepancies between the time constants that govern dCA in models and in experimental data. In this study, the processes that govern dCA are examined and it is proposed that the application of biophysical models remains limited due to a lack of understanding about the physical processes that are being modelled, partly due to the specific model formulation that has been most widely used (the equivalent electrical circuit). Based on the analysis presented here, it is proposed that the two most important time constants are arterial transit time and feedback time constant. It is therefore time to revisit equivalent electrical circuit models of dCA and to develop a more physiologically realistic alternative, one that can more easily be related to experimental data. KEY POINTS: Dynamic cerebral autoregulation is governed by two time constants. The first time constant is the arterial transit time, rather than the traditional 'RC' time constant widely used in previous models. This arterial transit time is approximately 1 s in the brain. The second time constant is the feedback time constant, which is less accurately known, although it is somewhat larger than the arterial transit time. The equivalent electrical circuit model of dynamic cerebral autoregulation should be replaced with a more physiologically representative model.