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.

Evaluation of aortic stenosis: From Bernoulli and Doppler to Navier-Stokes.

Uni-dimensional Doppler echocardiography data provide the mainstay of quantative assessment of aortic stenosis, with the transvalvular pressure drop a key indicator of haemodynamic burden. Sophisticated methods of obtaining velocity data, combined with improved computational analysis, are facilitating increasingly robust and reproducible measurement. Imaging modalities which permit acquisition of three-dimensional blood velocity vector fields enable angle-independent valve interrogation and calculation of enhanced measures of the transvalvular pressure drop. This manuscript clarifies the fundamental principles of physics that underpin the evaluation of aortic stenosis and explores modern techniques that may provide more accurate means to grade aortic stenosis and inform appropriate management.

Management of Patients With Severe Mitral Annular Calcification: JACC State-of-the-Art Review.

Mitral annular calcification (MAC) is a common and challenging pathologic condition, especially in the context of an aging society. Surgical mitral valve intervention in patients with MAC is difficult, with varying approaches to the calcified annular anatomy, and the advent of transcatheter valve interventions has provided additional treatment options. Advanced imaging provides the foundation for heart team discussions and management decisions concerning individual patients. This review focuses on the prognosis of, preoperative planning for, and management strategies for patients with MAC.

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.

Anatomy of a Transcatheter Mitral Valve Service.

Transcatheter mitral therapies offer treatment options to selected patients who are unable to undergo open procedures due to prohibitive surgical risk. Data detailing the design and structure of transcatheter mitral services to ensure appropriate patient selection and tailored management strategies is lacking. We report our initial experience of developing and running a purpose-built transcatheter mitral service. The nature and number of referral sources, the multi-disciplinary make-up of the dedicated Mitral Heart Team and the use of integrative imaging assessment with incorporation of computational solutions are discussed. In addition, a summary of the clinical decision-making process is presented. This report sets out a framework from which future clinics can evolve to improve and streamline the delivery of transcatheter mitral therapies.

Regional left ventricle scar detection from routine cardiac computed tomography angiograms using latent space classification.

OBJECTIVES: The aim of this study is to develop an automated method of regional scar detection on clinically standard computed tomography angiography (CTA) using encoder-decoder networks with latent space classification. BACKGROUND: Localising scar in cardiac patients can assist in diagnosis and guide interventions. Magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) is the clinical gold standard for scar imaging; however, it is commonly contraindicated. CTA is an alternative imaging modality that has fewer contraindications and is widely used as a first-line imaging modality of cardiac applications. METHODS: A dataset of 79 patients with both clinically indicated MRI LGE and subsequent CTA scans was used to train and validate networks to classify septal and lateral scar presence within short axis left ventricle slices. Two designs of encoder-decoder networks were compared, with one encoding anatomical shape in the latent space. Ground truth was established by segmenting scar in MRI LGE and registering this to the CTA images. Short axis slices were taken from the CTA, which served as the input to the networks. An independent external set of 22 cases (27% the size of the cross-validation set) was used to test the best network. RESULTS: A network classifying lateral scar only achieved an area under ROC curve of 0.75, with a sensitivity of 0.79 and specificity of 0.62 on the independent test set. The results of septal scar classification were poor (AUC < 0.6) for all networks. This was likely due to a high class imbalance. The highest AUC network encoded anatomical shape information in the network latent space, indicating it was important for the successful classification of lateral scar. CONCLUSIONS: Automatic lateral wall scar detection can be performed from a routine cardiac CTA with reasonable accuracy, without any scar specific imaging. This requires only a single acquisition in the cardiac cycle. In a clinical setting, this could be useful for pre-procedure planning, especially where MRI is contraindicated. Further work with more septal scar present is warranted to improve the usefulness of this approach.

"Gazing Into the Abyss": Transcatheter Mitral Valve-in-Valve Implantation Through a Cavernous Left Atrium.

We describe the case of a 73-year-old woman presenting with heart failure, a degenerating bioprosthetic mitral valve, and severely dilated left atrium, and highlight the role of multimodality imaging in planning transseptal transcatheter mitral valve-in-valve implantation. (Level of Difficulty: Advanced.).

The clinical significance and prognostic value of right ventricular wall tension in moderate or severe tricuspid regurgitation.

Background: We aim to explore the determinants of right ventricular wall tension (RV base-to-apex length multiplied by systolic pulmonary artery pressure [RV WT] and association with all-cause mortality in patients with moderate-to-severe tricuspid regurgitation. Materials & methods: Of total, 180 patients (71 ± 15 years, 54% females) were included. An increased RV WT was defined as >3300 mmHg x mm. Results: Patients with increased RV WT (n = 85, 47%) were more likely to be male and taller than patients with normal RV WT. In a multivariable-adjusted model, increased RV WT was associated with a 2.6-fold higher risk of all-cause mortality (HR: 2.59, 95% CI: 1.65-4.06). Conclusion: In patients with significant tricuspid regurgitation, an increased RV WT was common, and associated with a 2.6-fold higher risk of all-cause mortality. Male sex was the only independent determinant.

The advantages, pitfalls and limitations of guideline-directed medical therapy in patients with valvular heart disease.

Heart failure is an inevitable end-stage consequence of significant valvular heart disease (VHD) that is left untreated and increasingly encountered in an ageing society. Recent advances in transcatheter procedures and improved outcomes after valve surgery mean that intervention can (and should) be considered in all patients - even the elderly and those with multiple comorbidities - at earlier stages of the natural history of primary VHD, before the onset of irreversible left ventricular dysfunction (and frequently before the onset of symptoms). All patients with known VHD should be monitored carefully in the setting of a heart valve clinic and those who meet guideline criteria for surgical or transcatheter intervention referred for intervention without delay. High quality evidence for the use of medical therapy in VHD is limited and achieving target doses in an elderly and comorbid population frequently challenging. Furthermore, determining whether the valve or ventricle is the principal disease driver is crucial (although the distinction is not always binary, and often unclear). Guideline-directed medical therapy remains the mainstay of treatment for secondary mitral regurgitation - although up to 50% of patients may fail to respond and should be considered for cardiac resynchronization, transcatheter or surgical valve intervention. Early and definitive management strategies are essential and should be overseen by a specialist Heart Team that includes a Heart Failure specialist. In this article, we provide an evidence-based summary of approaches to the medical treatment of VHD and clinical guidance for the best management of patients in situations where high quality evidence is lacking.

Repeated stress dysregulates κ-opioid receptor signaling in the dorsal raphe through a p38α MAPK-dependent mechanism.

Repeated stress releases dynorphins and causes subsequent activation of κ-opioid receptors (KORs) in limbic brain regions. The serotonergic dorsal raphe nucleus (DRN) has previously been found to be an important site of action for the dysphoric effects of dynorphin-κ-opioid receptor system activation during stress-evoked behaviors, and KOR-induced activation of p38α mitogen-activated protein kinase (MAPK) in serotonergic neurons was found to be a critical mediator of the aversive properties of stress. Yet, how dynorphins and KORs functionally regulate the excitability of serotonergic DRN neurons both in adaptive and pathological stress states is poorly understood. Here we report that acute KOR activation by the selective agonist U69,593 [(+)-(5α,7α,8ß)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide] inhibits serotonergic neuronal excitability within the DRN through both presynaptic inhibition of excitatory synaptic transmission and postsynaptic activation of G-protein-gated inwardly rectifying potassium channels (GIRKs) electrophysiologically recorded in brain slices. C57BL/6 mice subjected to repeated swim, stress sessions had significantly reduced KOR-mediated GIRK currents recorded in serotonergic neurons in DRN postsynaptically, without significantly affecting presynaptic KOR-mediated regulation of excitatory transmission. This effect was blocked by genetic excision of p38α MAPK selectively from serotonergic neurons. An increase in phospho-immunoreactivity suggests that this functional dysregulation may be a consequence of tyrosine phosphorylation of GIRK (K(IR)3.1) channels. These data elucidate a mechanism for stress-induced dysregulation of the excitability of neurons in the DRN and identify a functional target of stress-induced p38α MAPK activation that may underlie some of the negative effects of pathological stress exposure.