Showing papers by "Paul Morris published in 2021"

Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis.

Abstract: Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.

Meta-analysis of echocardiographic quantification of left ventricular filling pressure.

Abstract: Aims The clinical reliability of echocardiographic surrogate markers of left ventricular filling pressures (LVFPs) across different cardiovascular pathologies remains unanswered. The main objective was to evaluate the evidence of how effectively different echocardiographic indices estimate true LVFP. Methods and results Design: this is a systematic review and meta‐analysis. Data source: Scopus, PubMed and Embase. Eligibility criteria for selecting studies were those that used echocardiography to predict or estimate pulmonary capillary wedge pressure or left ventricular end‐diastolic pressures. Twenty‐seven studies met criteria. Only eight studies (30%) reported both correlation coefficient and bias between non‐invasive and invasively measured LVFPs. The majority of studies (74%) recorded invasive pulmonary capillary wedge pressure as a surrogate for left ventricular end‐diastolic pressures. The pooled correlation coefficient overall was r = 0.69 [95% confidence interval (CI) 0.63–0.75, P < 0.01]. Evaluation by cohort demonstrated varying association: heart failure with preserved ejection fraction (11 studies, n = 575, r = 0.59, 95% CI 0.53–0.64) and heart failure with reduced ejection fraction (8 studies, n = 381, r = 0.67, 95% CI 0.61–0.72). Conclusions Echocardiographic indices show moderate pooled association to invasively measured LVFP; however, this varies widely with disease state. In heart failure with preserved ejection fraction, no single echocardiography‐based metric offers a reliable estimate. In heart failure with reduced ejection fraction, mitral inflow‐derived indices (E/e′, E/A, E/Vp, and EDcT) have reasonable clinical applicability. While an integrated approach of several echocardiographic metrics provides the most promise for estimating LVFP reliably, such strategies need further validation in larger, patient‐specific studies.

A novel method for measuring absolute coronary blood flow and microvascular resistance in patients with ischaemic heart disease.

Abstract: Aims Ischaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease, but is only a surrogate of flow and only predicts percentage flow changes. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory. Methods and Results A computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary microvascular resistance (MVR) using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, 3-D printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates (bias +2.08 mL/min; 95% CI (error range) -4.7 to + 8.8 mL/min; R2=0.999, p < 0.001; variability coefficient <1%). In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2=0.92, P < 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs ± 34 mL/min) and in vivo (±0.9 vs ± 24.4 mmHg). Conclusions Absolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management. Translational Perspective Current pressure wire-based methods of assessing coronary disease cannot assess absolute flow or microvascular disease. Our novel QCFD method, using only angiography-based CFD and a pressure wire, simultaneously measures FFR, absolute coronary blood flow rate, microvascular resistance and coronary flow reserve. QCFD is suitable for use in the catheter laboratory and requires no dedicated catheters, wires or infusions. QCFD measures blood flow and microvascular resistance in absolute units and allows microvascular and epicardial disease to be differentiated, quantified and separately assessed, with the potential to improve diagnostic accuracy and clinical management.

Reductions in biomarkers of exposure to selected harmful and potentially harmful constituents following exclusive and partial switching from combustible cigarettes to myblu™ electronic nicotine delivery systems (ENDS)

Abstract: Electronic nicotine delivery systems (ENDS) offer adult combustible cigarette smokers an alternative, potentially reduced harm, mode of nicotine delivery, attributed to fewer and reduced levels of harmful and potentially harmful constituents (HPHCs) in their aerosols compared to cigarette smoke. These two identical, randomised, open label, two-part studies aimed to compare levels of 15 biomarkers of exposure (BoE) to selected HPHCs associated with tobacco smoking in healthy US adult smoker subjects (n = 72). Following 9 days of exclusive use of a range of allocated myblu™ ENDS variants, subjects’ levels of 14 non-nicotine BoE were substantially reduced compared to baseline values (combustible cigarette use), in the range of 46–97%. BoE reductions were sustained in subjects who continued myblu use exclusively (n = 25) for a further 5 days, and returned to near baseline levels in subjects who returned to exclusive combustible cigarette use (n = 21). Dual users (n = 24) demonstrated reductions in BoE to a lesser extent than with exclusive myblu use. Measured nicotine equivalents did not significantly change throughout the study. These data suggest exclusive use of ENDS provides adult smokers seeking an alternative to combustible cigarettes with substantial reductions in HPHC exposures whilst achieving satisfying levels of nicotine delivery. Dual use involving substitution of cigarettes may also provide some of this advantage, but to lesser extent. Overall, the data contribute to the weight of evidence that ENDS are an important tool in tobacco harm reduction for adult smokers unwilling to or uninterested in quitting smoking. Study 1: NCT 04430634, study 2: NCT 04429932, clinicaltrials.gov (10-06-2020).

The new role of diagnostic angiography in coronary physiological assessment

Abstract: The role of ‘stand-alone’ coronary angiography (CAG) in the management of patients with chronic coronary syndromes is the subject of debate, with arguments for its replacement with CT angiography on the one hand and its confinement to the interventional cardiac catheter laboratory on the other. Nevertheless, it remains the standard of care in most centres. Recently, computational methods have been developed in which the laws of fluid dynamics can be applied to angiographic images to yield ‘virtual’ (computed) measures of blood flow, such as fractional flow reserve. Together with the CAG itself, this technology can provide an ‘all-in-one’ anatomical and functional investigation, which is particularly useful in the case of borderline lesions. It can add to the diagnostic value of CAG by providing increased precision and reduce the need for further non-invasive and functional tests of ischaemia, at minimal cost. In this paper, we place this technology in context, with emphasis on its potential to become established in the diagnostic workup of patients with suspected coronary artery disease, particularly in the non-interventional setting. We discuss the derivation and reliability of angiographically derived fractional flow reserve (CAG-FFR) as well as its limitations and how CAG-FFR could be integrated within existing national guidance. The assessment of coronary physiology may no longer be the preserve of the interventional cardiologist.

Operator-dependent variability of angiography-derived fractional flow reserve and the implications for treatment.

Abstract: Aims To extend the benefits of physiologically guided percutaneous coronary intervention to many more patients, angiography-derived, or 'virtual' fractional flow reserve (vFFR) has been developed, in which FFR is computed, based upon the images, instead of being measured invasively. The effect of operator experience with these methods upon vFFR accuracy remains unknown. We investigated variability in vFFR results based upon operator experience with image-based computational modelling techniques. Methods and results Virtual fractional flow reserve was computed using a proprietary method (VIRTUheart) from the invasive angiograms of patients with coronary artery disease. Each case was processed by an expert (>100 vFFR cases) and a non-expert (<20 vFFR cases) operator and results were compared. The primary outcome was the variability in vFFR between experts and non-experts and the impact this had upon treatment strategy (PCI vs. conservative management). Two hundred and thirty-one vessels (199 patients) were processed. Mean non-expert and expert vFFRs were similar overall [0.76 (0.13) and 0.77 (0.16)] but there was significant variability between individual results (variability coefficient 12%, intraclass correlation coefficient 0.58), with only moderate agreement (κ = 0.46), and this led to a statistically significant change in management strategy in 27% of cases. Variability was significantly lower, and agreement higher, for expert operators; a change in their recommended management occurred in 10% of repeated expert measurements and 14% of inter-expert measurements. Conclusion Virtual fractional flow reserve results are influenced by operator experience of vFFR processing. This had implications for treatment allocation. These results highlight the importance of training and quality assurance to ensure reliable, repeatable vFFR results.

The importance of three dimensional coronary artery reconstruction accuracy when computing virtual fractional flow reserve from invasive angiography.

Abstract: Three dimensional (3D) coronary anatomy, reconstructed from coronary angiography (CA), is now being used as the basis to compute ‘virtual’ fractional flow reserve (vFFR), and thereby guide treatment decisions in patients with coronary artery disease (CAD). Reconstruction accuracy is therefore important. Yet the methods required remain poorly validated. Furthermore, the magnitude of vFFR error arising from reconstruction is unkown. We aimed to validate a method for 3D CA reconstruction and determine the effect this had upon the accuracy of vFFR. Clinically realistic coronary phantom models were created comprosing seven standard stenoses in aluminium and 15 patient-based 3D-printed, imaged with CA, three times, according to standard clinical protocols, yielding 66 datasets. Each was reconstructed using epipolar line projection and intersection. All reconstructions were compared against the real phantom models in terms of minimal lumen diameter, centreline and surface similarity. 3D-printed reconstructions (n = 45) and the reference files from which they were printed underwent vFFR computation, and the results were compared. The average error in reconstructing minimum lumen diameter (MLD) was 0.05 (± 0.03 mm) which was < 1% (95% CI 0.13–1.61%) compared with caliper measurement. Overall surface similarity was excellent (Hausdorff distance 0.65 mm). Errors in 3D CA reconstruction accounted for an error in vFFR of ± 0.06 (Bland Altman 95% limits of agreement). Errors arising from the epipolar line projection method used to reconstruct 3D coronary anatomy from CA are small but contribute to clinically relevant errors when used to compute vFFR.

Feasibility and validation of trans-valvular flow derived by four-dimensional flow cardiovascular magnetic resonance imaging in patients with atrial fibrillation.

Abstract: Background: Four-dimensional (4D) flow cardiovascular magnetic resonance imaging (MRI) is an emerging technique used for intra-cardiac blood flow assessment. The role of 4D flow cardiovascular MRI in the assessment of trans-valvular flow in patients with atrial fibrillation (AF) has not previously been assessed. The purpose of this study was to assess the feasibility, image quality, and internal validity of 4D flow cardiovascular MRI in the quantification of trans-valvular flow in patients with AF. Methods: Patients with AF and healthy controls in sinus rhythm underwent cardiovascular MRI, including 4D flow studies. Quality assurance checks were done on the raw data and streamlines. Consistency was investigated by trans-valvular flow assessment between the mitral valve (MV) and the aortic valve (AV). Results: Eight patients with AF (88% male, mean age 62±13 years, mean heart rate (HR) 83±16 beats per minute (bpm)) were included and compared with ten healthy controls (70% male, mean age 41±20 years, mean HR 68.5±9 bpm). All scans were of either good quality with minimal blurring artefacts, or excellent quality with no artefacts. No significant bias was observed between the AV and MV stroke volumes in either healthy controls (-4.8, 95% CI -15.64 to 6.04; P=0.34) or in patients with AF (1.64, 95% CI -4.7 to 7.94; P=0.56). A significant correlation was demonstrated between MV and AV stroke volumes in both healthy controls (r=0.87, 95% CI 0.52 to 0.97; P=0.001) and in AF patients (r=0.82, 95% CI 0.26 to 0.97; P=0.01). Conclusions: In patients with AF, 4D flow cardiovascular MRI is feasible with good image quality, allowing for quantification of trans-valvular flow.

Under the skin: Exploring 2-month-olds' thermal reactions in different social interactions with mother and stranger.

Abstract: Physiological adaptations to external stressors can reveal socio-cognitive health in infancy. With the use of thermal imaging and behavioural analyses, the current study examined the arousal markers accompanying infants' interactions with a familiar and an unfamiliar person. To address the current research question, the mother and a complete stranger interacted with 2 to 3 month-old infants (N= 10, 2 boys)in three different conditions: Neutral, Play, and Compliment. Behavioral analyses showed that overall gaze was longer to the Stranger compared to the Mother independent of condition. Physiological findings showed that skin temperature was significantly higher with the stranger independent of condition. The regions of the face that passed the significance threshold included the maxillary area, the nose, and the forehead. Both behavioral and physiological findings emphasize the ability of the infant to distinguish between a familiar and an unfamiliar person. Most importantly, however thermal imaging has proven to be a promising tool in physiologically differentiating between variable social conditions in very young infants opening up a new experimental portal for identifying healthy physiological development.

Virtual (Computed) Fractional Flow Reserve: Future Role in Acute Coronary Syndromes.

Abstract: The current management of acute coronary syndromes (ACS) is with an invasive strategy to guide treatment. However, identifying the lesions which are physiologically significant can be challenging. Non-invasive imaging is generally not appropriate or timely in the acute setting, so the decision is generally based upon visual assessment of the angiogram, supplemented in a small minority by invasive pressure wire studies using fractional flow reserve (FFR) or related indices. Whilst pressure wire usage is slowly increasing, it is not feasible in many vessels, patients and situations. Limited evidence for the use of FFR in non-ST elevation (NSTE) ACS suggests a 25% change in management, compared with traditional assessment, with a shift from more to less extensive revascularisation. Virtual (computed) FFR (vFFR), which uses a 3D model of the coronary arteries constructed from the invasive angiogram, and application of the physical laws of fluid flow, has the potential to be used more widely in this situation. It is less invasive, fast and can be integrated into catheter laboratory software. For severe lesions, or mild disease, it is probably not required, but it could improve the management of moderate disease in 'real time' for patients with non-ST elevation acute coronary syndromes (NSTE-ACS), and in bystander disease in ST elevation myocardial infarction. Its practicability and impact in the acute setting need to be tested, but the underpinning science and potential benefits for rapid and streamlined decision-making are enticing.

The relationship between coronary stenosis morphology and fractional flow reserve: a computational fluid dynamics modelling study

Abstract: International guidelines mandate the use of fractional flow reserve (FFR) and/or non-hyperaemic pressure ratios to assess the physiological significance of moderate coronary artery lesions to guide revascularization decisions. However, they remain underused such that visual estimation of lesion severity continues to be the predominant decision-making tool. It would be pragmatic to have an improved understanding of the relationship between lesion morphology and haemodynamics. The aim of this study was to compute virtual FFR (vFFR) in idealized coronary artery geometries with a variety of stenosis and vessel characteristics. Coronary artery geometries were modelled, based upon physiologically realistic branched arteries. Common stenosis characteristics were studied, including % narrowing, length, eccentricity, shape, number, position relative to branch, and distal (myocardial) resistance. Computational fluid dynamics modelling was used to calculate vFFRs using the VIRTUheart™ system. Percentage lesion severity had the greatest effect upon FFR. Any ≥80% diameter stenosis in two views (i.e. concentric) was physiologically significant (FFR ≤ 0.80), irrespective of length, shape, or vessel diameter. Almost all eccentric stenoses and all 50% concentric stenoses were physiologically non-significant, whilst 70% uniform concentric stenoses about 10 mm long straddled the ischaemic threshold (FFR 0.80). A low microvascular resistance (MVR) reduced FFR on average by 0.05, and a high MVR increased it by 0.03. Using computational modelling, we have produced an analysis of vFFR that relates stenosis characteristics to haemodynamic significance. The strongest predictor of a positive vFFR was a concentric, ≥80% diameter stenosis. The importance of MVR was quantified. Other lesion characteristics have a limited impact.

Cardiovascular examination using hand-held cardiac ultrasound

Abstract: Echocardiography is the first-line imaging modality for assessing cardiac function and morphology. The miniaturisation of ultrasound technology has led to the development of hand-held cardiac ultrasound (HCU) devices. The increasing sophistication of available HCU devices enables clinicians to more comprehensively examine patients at the bedside. HCU can augment clinical exam findings by offering a rapid screening assessment of cardiac dysfunction in both the Emergency Department and in cardiology clinics. Possible implications of implementing HCU into clinical practice are discussed in this review paper.

A further explanation for chest pain without visible coronary artery disease.

Abstract: Editor – we read with interest the review and recommendations by Rogers et al on how to identify and manage functional cardiac symptoms.[1][1] The messages resonate with our experiences both on the acute take and in the clinic. The authors refer to ‘syndrome x’ as an alternative name for non-

An Encounter With Lattice Boltzmann for Biomedical Applications: Interactive Simulation to Support Clinical and Design Decisions

Abstract: Medical device design for personalised medicine requires sophisticated tools for optimisation of biomechanical and biofluidic devices. This paper investigates a new real-time tool for simulating structural and fluid scenarios - ANSYS Discovery Live - and we evaluate its capability in the fluid domain through benchmark flows that all involve steady state flow at the inlet and zero pressure at the outlet. Three scenarios are reported: i. Laminar flow in a straight pipe, ii. vortex shedding from the Karman Vortex, and iii. nozzle flows as characterised by an FDA benchmark geometry. The solver uses a Lattice Boltzmann method requiring a high performance GPU (nVidiaGTX1080, 8GB RAM). Results in each case were compared with the literature and demonstrated credible solutions, all delivered in near real-time: i. The straight pipe delivered parabolic flow after an appropriate entrance length (plug flow inlet conditions), ii. the Karman Vortex demonstrated appropriate vortex shedding as a function of Reynolds number, characterised by Strouhal number in both the free field and within a pipe, and ii the FDA benchmark geometry generated results consistent with the literature in terms of variation of velocity along the centreline and in the radial direction, although deviation from experimental validation was evident in the sudden expansion section of the geometry. This behaviour is similar to previous reported results from Navier-Stokes solvers. A cardiovascular stenosis example is also considered, to provide a more direct biomedical context. The current software framework imposes constraints on inlet/outlet boundary conditions, and only supports limited control of solver discretization without providing full field vector flow data outputs. Nonetheless, numerous benefits result from the interactive interface and almost-real-time solution, providing a tool that may help to accelerate the arrival of improved patient-specific medical devices.

Is threat in the way they move? Influences of static and gait information on threat judgments of unknown people

Abstract: Recognising intraspecies threat is essential for survival. However, this needs to be balanced against the undue avoidance of unknown others who may be useful to us. Research has shown that judgments of ‘aggression’ and ‘threat’ posed by an unknown person can accurately reflect that person’s general aggressive tendencies. To date, there has not been a within-sample comparison of the informativeness of static and walking stimuli for threat judgments. In this study, 193 participants rated the threat posed by 23 target people presented as both simplified gait presentations (point-light walkers) and still images. We analysed how threat judgments made by participants were predicted by the target’s self-reported aggression (accuracy), the sex of the targets and the medium of target presentation (point-light vs. still image). Our results showed that participants’ threat judgments accurately predicted targets’ aggression. Male targets received higher threat ratings than female targets and point-light displays were rated as more threatening than still images. There were no effects of target sex and presentation medium on accuracy of threat perception and no sex by medium interactions on judgments themselves. Overall, this study provides further evidence of the accuracy of threat judgments at detecting trait aggression. However, further research is needed to explain what features of the target people are enabling the accurate judgments of aggression.