Aortic Stenosis: Haemodynamic Benchmark and Metric Reliability Study.

Aortic stenosis is a condition which is fatal if left untreated. Novel quantitative imaging techniques which better characterise transvalvular pressure drops are being developed but require refinement and validation. A customisable and cost-effective workbench valve phantom circuit capable of replicating valve mechanics and pathology was created. The reproducibility and relationship of differing haemodynamic metrics were assessed from ground truth pressure data alongside imaging compatibility. The phantom met the requirements to capture ground truth pressure data alongside ultrasound and magnetic resonance image compatibility. The reproducibility was successfully tested. The robustness of three different pressure drop metrics was assessed: whilst the peak and net pressure drops provide a robust assessment of the stenotic burden in our phantom, the peak-to-peak pressure drop is a metric that is confounded by non-valvular factors such as wave reflection. The peak-to-peak pressure drop is a metric that should be reconsidered in clinical practice. The left panel shows manufacture of low cost, functional valves. The central section demonstrates circuit layout, representative MRI and US images alongside gross valve morphologies. The right panel shows the different pressure drop metrics that were assessed for reproducibility.

Non-invasive cardiovascular magnetic resonance assessment of pressure recovery distance after aortic valve stenosis.

BACKGROUND: Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40-50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. METHODS: We developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. RESULTS: In-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40-50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. CONCLUSION: The non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.

Blood speckle imaging compared with conventional Doppler ultrasound for transvalvular pressure drop estimation in an aortic flow phantom.

BACKGROUND: Transvalvular pressure drops are assessed using Doppler echocardiography for the diagnosis of heart valve disease. However, this method is highly user-dependent and may overestimate transvalvular pressure drops by up to 54%. This work aimed to assess transvalvular pressure drops using velocity fields derived from blood speckle imaging (BSI), as a potential alternative to Doppler.  METHODS: A silicone 3D-printed aortic valve model, segmented from a healthy CT scan, was placed within a silicone tube. A CardioFlow 5000MR flow pump was used to circulate blood mimicking fluid to create eight different stenotic conditions. Eight PendoTech pressure sensors were embedded along the tube wall to record ground-truth pressures (10 kHz). The simplified Bernoulli equation with measured probe angle correction was used to estimate pressure drop from maximum velocity values acquired across the valve using Doppler and BSI with a GE Vivid E95 ultrasound machine and 6S-D cardiac phased array transducer. RESULTS: There were no significant differences between pressure drops estimated by Doppler, BSI and ground-truth at the lowest stenotic condition (10.4 ± 1.76, 10.3 ± 1.63 vs. 10.5 ± 1.00 mmHg, respectively; p > 0.05). Significant differences were observed between the pressure drops estimated by the three methods at the greatest stenotic condition (26.4 ± 1.52, 14.5 ± 2.14 vs. 20.9 ± 1.92 mmHg for Doppler, BSI and ground-truth, respectively; p < 0.05). Across all conditions, Doppler overestimated pressure drop (Bias = 3.92 mmHg), while BSI underestimated pressure drop (Bias = -3.31 mmHg). CONCLUSIONS: BSI accurately estimated pressure drops only up to 10.5 mmHg in controlled phantom conditions of low stenotic burden. Doppler overestimated pressure drops of 20.9 mmHg. Although BSI offers a number of theoretical advantages to conventional Doppler echocardiography, further refinements and clinical studies are required with BSI before it can be used to improve transvalvular pressure drop estimation in the clinical evaluation of aortic stenosis.

Unlocking the Non-invasive Assessment of Conduit and Reservoir Function in the Aorta : The Obstructive Descending Aorta in HLHS.

Aortic surgeries in congenital conditions, such as hypoplastic left heart syndrome (HLHS), aim to restore and maintain the conduit and reservoir functions of the aorta. We proposed a method to assess these two functions based on 4D flow MRI, and we applied it to study the aorta in pre-Fontan HLHS. Ten pre-Fontan HLHS patients and six age-matched controls were studied to derive the advective pressure difference and viscous dissipation for conduit function, and pulse wave velocity and elastic modulus for reservoir function. The reconstructed neo-aorta in HLHS subjects achieved a good conduit function at a cost of an impaired reservoir function (69.7% increase of elastic modulus). The native descending HLHS aorta displayed enhanced reservoir (elastic modulus being 18.4% smaller) but impaired conduit function (three-fold increase in peak advection). A non-invasive and comprehensive assessment of aortic conduit and reservoir functions is feasible and has potentially clinical relevance in congenital vascular conditions.

Septal curvature as a robust and reproducible marker for basal septal hypertrophy.

BACKGROUND: Basal septal hypertrophy (BSH) is an asymmetric, localized thickening of the upper interventricular septum and constitutes a marker of an early remodelling in patients with hypertension. This morphological trait has been extensively researched because of its prevalence in hypertension, yet its clinical and prognostic value for individual patients remains undetermined. One of the reasons is the lack of a reliable and reproducible metric to quantify the presence and the extent of BSH. This article proposes the use of the curvature of the left ventricular endocardium as a robust feature for BSH characterization, and as an objective criterion to quantify current subjective 'visual assessment' of the presence of sigmoidal septum. The proposed marker, called average septal curvature, is defined as the inverse of the radius adjacent to each point of the endocardial contour along the basal and mid inferoseptal segments of the left ventricle. METHOD: Robustness and reproducibility were assessed on a cohort of 220 patients, including 161 hypertensive patients (32 with BSH) and 59 healthy controls. RESULTS: The results show that compared with the conventionally used wall thickness metrics, the new marker is more reproducible (relative standard deviation of errors of 7 vs. 13%, and 8 vs. 38% for intra-observer and inter-observer variability, respectively) and better correlates to the functional parameters related to BSH, with main difference (absolute rank correlation 0.417 vs. 0.341) in local deformation changes assessed by longitudinal strain. CONCLUSION: Average septal curvature is a more precisely defined and reproducible metric than thickness ratios, it can be fully automated, and better infers the functional remodelling related to hypertension.

Basal Ventricular Septal Hypertrophy in Systemic Hypertension.

Basal septal hypertrophy (BSH) is commonly seen in patients with systemic hypertension and has been associated with increased afterload. The impact of localized hypertrophy on left ventricular (LV) and left atrial (LA) function is still unclear. Our aim is to investigate if BSH is a marker of a more pronounced impact of hypertension on cardiac function in the early stages of hypertensive heart disease. An echocardiogram was performed in 163 well-controlled hypertensive patients and 22 healthy individuals. BSH was defined by a basal-to-mid septal thickness ratio ≥1.4. LV dimensions and mass were evaluated. LV global and regional deformation was assessed by 2-dimensional (2D) speckle tracking echocardiography, and LV diastolic function by 2D and Doppler imaging. LA function was evaluated with phasic volume indices calculated from 2D and 3-dimensional volumes, as well as speckle tracking echocardiography. The population was 54% men, mean age 57 (53 to 60) years. BSH was seen in 20% (n = 32) of the hypertensive cohort. Patients with BSH showed decreased regional LV systolic deformation, impaired LV relaxation with a higher proportion of indeterminate LV diastolic function, and LA functional impairment defined by a reduction of reservoir strain and a change in LA functional dynamics. In conclusion, in well-controlled hypertension impairment of LV and LA function is present in patients with early LV remodeling and localized hypertrophy. BSH might be useful as an early marker of the burden of hypertensive heart disease.

Impact of valve morphology, hypertension and age on aortic wall properties in patients with coarctation: a two-centre cross-sectional study.

OBJECTIVE: We aimed to investigate the combined effects of arterial hypertension, bicuspid aortic valve disease (BAVD) and age on the distensibility of the ascending and descending aortas in patients with aortic coarctation. DESIGN: Cross-sectional study. SETTING: The study was conducted at two university medical centres, located in Berlin and London. PARTICIPANTS: A total of 121 patients with aortic coarctation (ages 1-71 years) underwent cardiac MRI, echocardiography and blood pressure measurements. OUTCOME MEASURES: Cross-sectional diameters of the ascending and descending aortas were assessed to compute aortic area distensibility. Findings were compared with age-specific reference values. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology statement and reporting guidelines. RESULTS: Impaired distensibility (below fifth percentile) was seen in 37% of all patients with coarctation in the ascending aorta and in 43% in the descending aorta. BAVD (43%) and arterial hypertension (72%) were present across all ages. In patients >10 years distensibility impairment of the ascending aorta was predominantly associated with BAVD (OR 3.1, 95% CI 1.33 to 7.22, p=0.009). Distensibility impairment of the descending aorta was predominantly associated with arterial hypertension (OR 2.8, 95% CI 1.08 to 7.2, p=0.033) and was most pronounced in patients with uncontrolled hypertension despite antihypertensive treatment. CONCLUSION: From early adolescence on, both arterial hypertension and BAVD have a major impact on aortic distensibility. Their specific effects differ in strength and localisation (descending vs ascending aorta). Moreover, adequate blood pressure control is associated with improved distensibility. These findings could contribute to the understanding of cardiovascular complications and the management of patients with aortic coarctation.

Surrogates for myocardial power and power efficiency in patients with aortic valve disease.

We aimed to assess surrogate markers for left ventricular (LV) myocardial power and efficiency in patients with isolated aortic stenosis (AS) and combined stenosis/regurgitation (AS/AR). In AS (n = 59), AS/AR (n = 21) and controls (n = 14), surrogates for LV myocardial power and circulatory/external myocardial efficiency were obtained from cardiac MRI. Median surrogate LV myocardial power was increased in AS, 7.7 W/m2 (interquartile range 6.0-10.2; p = 0.010) and AS/AR, 10.8 W/m2 (8.9-13.4; p < 0.001) when compared to controls, 5.4 W/m2 (4.2-6.5), and was lower in AS than AS/AR (p < 0.001). Surrogate circulatory efficiency was decreased in AS, 8.6% (6.8-11.1; p < 0.001) and AS/AR, 5.4% (4.1-6.2; p < 0.001) when compared to controls, 11.8% (9.8-16.9). Surrogate external myocardial efficiency was higher in AS, 15.2% (11.9-18.6) than in AS/AR, 12.2% (10.1-14.2; p = 0.031) and was significantly lower compared to controls, 12.2% (10.7-18.1) in patients with reduced ejection fraction (EF), 9.8% (8.1-11.7; p = 0.025). In 16% of all cases, left ventricular mass/volume indices and EF were within normal ranges, wheras surrogate LV myocardial power was elevated and patients were symptomatic. Although influenced by pressure/volume load, the myocardium is additionally affected by remodelling processes. Surrogates for circulatory efficiency and LV myocardial power gradually reflect alterations in patients with AS and AS/AR, even when surrogate external myocardial efficiency, EF, mass and volume indices still remain compensated.

Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model.

Ectopic beats are known to be involved in the initiation of a variety of cardiac arrhythmias. Although their location may vary, ectopic excitations have been found to originate from infarct areas, regions of micro-fibrosis and other heterogeneous tissues. However, the underlying mechanisms that link ectopic foci to heterogeneous tissues have yet to be fully understood. In this work, we investigate the mechanism of micro-reentry that leads to the generation of ectopic beats near infarct areas using a patient-specific heart model. The patient-specific geometrical model of the heart, including scar and peri-infarct zones, is obtained through magnetic resonance imaging (MRI). The infarct region is composed of ischemic myocytes and non-conducting cells (fibrosis, for instance). Electrophysiology is captured using an established cardiac myocyte model of the human ventricle modified to describe ischemia. The simulation results clearly reveal that ectopic beats emerge from micro-reentries that are sustained by the heterogeneous structure of the infarct regions. Because microscopic information about the heterogeneous structure of the infarct regions is not available, Monte-Carlo simulations are used to identify the probabilities of an infarct region to behave as an ectopic focus for different levels of ischemia and different percentages of non-conducting cells. From the proposed model, it is observed that ectopic beats are generated when a percentage of non-conducting cells is near a topological metric known as the percolation threshold. Although the mechanism for micro-reentries was proposed half a century ago to be a source of ectopic beats or premature ventricular contractions during myocardial infarction, the present study is the first to reproduce this mechanism in-silico using patient-specific data.

Right ventricular energetics and power in pulmonary regurgitation vs. stenosis using four dimensional phase contrast magnetic resonance.

OBJECTIVE: We investigated a full energetic profile of pressure and volume loaded right ventricle (RV) in porcine models by evaluating kinetic energy (KE), stroke power, power output and power loss across pulmonary valves with stenosis (PS) or with regurgitation (PR). METHODS: Fifteen pigs (6 PS and 6 PR, 3 unoperated controls) were studied. Phase-contrast 4D-flow MRI was performed in models of PS and PR at baseline and at 10-12 weeks, in conjunction with cardiac catheterization. Phase contrast velocities over 1 cardiac cycle were registered with a dynamic mask of the RV segmented from cine images. Mean KE and KE curve profiles were measured, normalized for RV volumes and compared between groups. Right heart catheterization pressures were used to calculate RV stroke power and power output, from which pulmonary valve power loss and RV power output ratio were calculated, and compared between groups. RESULTS: PS and PR groups had similar KE pre procedure but significant changes in KE post procedure. The PR group had higher RV power output ratio and KE (72.1% ±â€¯11.4%; 20.6 ±â€¯6.1) than PS group (25.6% ±â€¯4.7%; 13.8 ±â€¯5.0) post procedure. Volume loaded RV from PR had higher KE and power output ratio compared to pressure load from PS. CONCLUSIONS: In porcine models of PS and PR, the RV presents altered systolic and diastolic energetic profiles. Pulmonary valve efficiency appeared to decrease in the medium term with somatic growth, with increased power loss in all groups studied, and greatly within the PS group.

Beyond Pressure Gradients: The Effects of Intervention on Heart Power in Aortic Coarctation.

BACKGROUND: In aortic coarctation, current guidelines recommend reducing pressure gradients that exceed given thresholds. From a physiological standpoint this should ideally improve the energy expenditure of the heart and thus prevent long term organ damage. OBJECTIVES: The aim was to assess the effects of interventional treatment on external and internal heart power (EHP, IHP) in patients with aortic coarctation and to explore the correlation of these parameters to pressure gradients obtained from heart catheterization. METHODS: In a collective of 52 patients with aortic coarctation 25 patients received stenting and/or balloon angioplasty, and 20 patients underwent MRI before and after an interventional treatment procedure. EHP and IHP were computed based on catheterization and MRI measurements. Along with the power efficiency these were combined in a cardiac energy profile. RESULTS: By intervention, the catheter gradient was significantly reduced from 21.8±9.4 to 6.2±6.1mmHg (p<0.001). IHP was significantly reduced after intervention, from 8.03±5.2 to 4.37±2.13W (p < 0.001). EHP was 1.1±0.3 W before and 1.0±0.3W after intervention, p = 0.044. In patients initially presenting with IHP above 5W intervention resulted in a significant reduction in IHP from 10.99±4.74 W to 4.94±2.45W (p<0.001), and a subsequent increase in power efficiency from 14 to 26% (p = 0.005). No significant changes in IHP, EHP or power efficiency were observed in patients initially presenting with IHP < 5W. CONCLUSION: It was demonstrated that interventional treatment of coarctation resulted in a decrease in IHP. Pressure gradients, as the most widespread clinical parameters in coarctation, did not show any correlation to changes in EHP or IHP. This raises the question of whether they should be the main focus in coarctation interventions. Only patients with high IHP of above 5W showed improvement in IHP and power efficiency after the treatment procedure. TRIAL REGISTRATION: clinicaltrials.gov NCT02591940.

MRI as a tool for non-invasive vascular profiling: a pilot study in patients with aortic coarctation.

AIM: While the overall concept of aortic coarctation has changed from one of simple obstruction to one that includes significant vascular dysfunction, this has not yet been translated into the diagnostic and treatment process. To close this gap, we sought to demonstrate the usefulness of an additional non-invasive vascular profile. METHOD: During a pilot study in eight coarctation patients, aortic area compliance, aortic distensibility, time phase shift and blood flow (distribution) were calculated from cine-MRI and 2D-/4D-velocity-encoded MRI sequences. RESULTS: Compared to healthy individuals, a significantly lower aortic compliance and reduced flow to the descending aorta were found in patients with coarctation. DISCUSSION: These differences underline the potential usefulness of a combined vascular profile in coarctation patients. CONCLUSION: It was successfully shown that functional vascular profiling of the aorta is feasible to be acquired non-invasively in a clinical setting and can provide additional diagnostic information. These can be the key input parameters for computational fluid dynamics-modeling.

Hemodynamic and energetic aspects of the left ventricle in patients with mitral regurgitation before and after mitral valve surgery.

BACKGROUND: The role of intracardiac blood flow behavior within the context of manifestation and interventional success in patients with mitral regurgitation is unknown to date. The present study aims to assess left ventricular blood flow behavior characterized by kinetic energy (KE) in patients with mitral regurgitation before and after mitral valve surgery. METHODS: Patients with mitral regurgitation (mean age 56 ± 9 years) and the necessity for mitral valve repair (n = 6) or biological valve replacement (n = 4) received cardiac magnetic resonance before and after surgery and were compared with a group of healthy volunteers (n = 7; mean age 27 ± 7 years). Volumetric data and KE of the left ventricle were obtained for all subjects. KE normalized and nonnormalized to volume was calculated from four-dimensional flow magnetic resonance imaging. Mean KE and KE peaks (systolic, early-diastolic and late diastolic), and end-systolic phase duration were considered. RESULTS: End-diastolic, end-systolic and stroke volume were significantly higher in patients with mitral regurgitation than in healthy volunteers (P = 0.00, 0.01, and 0.00, respectively) and decreased significantly after surgery (P = 0.00, 0.01, and 0.00, respectively). A significant postoperative decrease of mean KE, systolic and early-diastolic KE peaks was observed (P = 0.01, 0.02, and 0.01, respectively). Late-diastolic KE peak remained high in postoperative patients (P = 0.58). CONCLUSION: Intracardiac blood flow as characterized by measurements of KE is altered in patients with mitral regurgitation. Physiological flow conditions appear to not fully be restored with mitral valve surgery.

Pressure fields by flow-sensitive, 4D, velocity-encoded CMR in patients with aortic coarctation.

This study compared pressure fields by 4-dimensional (4D), velocity-encoded cine (VEC) cardiac magnetic resonance imaging (CMR) with pressures measured by the clinical gold standard catheterization. Thirteen patients (n = 7 male, n = 6 female) with coarctation were studied. The 4D-VEC-CMR pressure fields were computed by solving the Pressure-Poisson equation. The agreement between catheterization and CMR-based methods was determined at 5 different measurement sites along the aorta. For all sites, the correlation coefficients between measures varied between 0.86 and 0.97 (p < 0.001). The Bland-Altman test showed good agreement between peak systolic pressure gradients across the coarctation. The nonsignificant (p > 0.2) bias was +2.3 mm Hg (± 6.4 mm Hg, 2 SDs) for calibration with dynamic pressures and +1.5 mm Hg (± 4.6 mm Hg, 2 SDs) for calibration with static pressure. In a clinical setting of coarctation, pressure fields can be accurately computed from 4D-VEC-CMR-derived flows. In patients with coarctation, this noninvasive technique might evolve to an alternative to invasive catheterization.