Analysis of local hemodynamics in central and peripheral arteries

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.To understand the function of the cardiovascular system, the propagation of waves in arteries has to be investigated, since they carry information which can be used for the prevention and diagnosis of cardiovascular diseases. The main goal of this thesis is to improve the understanding of wave propagation in central and peripheral arteries studying the local hemodynamics of the ascending aorta, the carotid artery and the femoral artery by analysing human, animal and in vitro data. Also, another aim is to introduce a technique for non-invasive determination of the local arterial distensibility, the wave speed, and wave intensities. Arterial hemodynamics is here studied using wave intensity analysis, a time domain technique based on pressure and velocity measurements that is derived from the 1D theory of wave propagation in elastic tubes. Also, variations of this technique were used, such as (i) the non-invasive wave intensity analysis that relies on diameter and velocity measurements and (ii) the reservoir-wave approach in which pressure is considered the sum of a pressure due to the elastic properties of the arteries and a pressure due to the travelling wave. To identify the correct analysis to describe the wave propagation in the ascending aorta using pressure and velocity measurements, the hemodynamics of the canine ascending aorta was studied invasively using the traditional wave intensity (or waveonly) analysis and the reservoir-wave approach in both control condition and during total aorta occlusions in order to provide clear reflection sites. The models produced a remarkably similar wave intensity curves, although the intensity magnitudes were different. The reservoir-wave model always yielded lower values for all hemodynamic parameters studied. Both models led to the conclusion that distal occlusions have little or no effect on hemodynamics in the ascending aorta. Since the ascending aorta is not an accessible vessel its examination in clinical routine is challenging. More superficial arteries, such as carotid, radial, brachial and femoral arteries, might be easier to examine, in particular using ultrasound equipment that is normally available in the clinic. These considerations led to the second study of this thesis that is the introduction of a new technique for the non-invasive determination of arterial distensibility, local wave speed and wave intensities to study arterial hemodynamics in humans. The technique relies only on diameter and velocity measurements that can be obtained using ultrasound. In particular, the technique was used for the first time to study the hemodynamic of the carotid and femoral arteries in a large population of healthy humans to investigate the changes with age and gender. The carotid artery was more affected by the aging process than the femoral artery, even in healthy subjects. Local wave speed, distensibility and hemodynamic wave intensity parameters (except the reflection index) had strong correlations with age at the carotid artery. The mechanical properties and hemodynamic parameters of the femoral artery were not significantly age-dependent, but local wave speed, distensibility and forward wave intensity were significantly gender-dependent. The findings of the first and second studies contributed to the design of the third study. The carotid artery is an elastic artery relatively close to the heart and thus the hemodynamics of this vessel is related to left ventricular function. For this reason, the carotid hemodynamics of the same healthy population was investigated for the first time using the reservoir-wave approach. Pressure and velocity measurements were separated into their reservoir and excess components and the effects of age and gender on these parameters were studied. It was found that in the carotid artery reservoir and excess components are strongly affected by the ageing process. From the above studies some questions about the hemodynamics of central arteries remained unsolved. For this reason it was decided to carry out in vitro experiments in a mock circulatory system to investigate the effects of variation of compliance and stroke volume on the reservoir and excess pressure components of the ascending aorta. This allows for the study of different physiological and pathological conditions, such as age, hypertension, atherosclerosis and ventricular dysfunction in relation to vascular compliance and stroke volume. The reservoir and excess components of the measured pressure wave were both significantly related to aortic compliance and stroke volume, but the reservoir pressure had a stronger relationship with aortic compliance compared with the excess pressure and its magnitude increased more significantly when the aorta became stiffer. Wave speeds, calculated using measured and excess pressures, followed the same pattern, but the one calculated using excess pressure was smaller than the other. Wave speed was strongly related to aortic compliance, but not to the change of stroke volume. In conclusion, the use of the wave-only and the reservoir-wave models led to different values of wave speed and intensities that can be explained considering the anatomy of the arterial system. Notably, elastic and muscular arteries are differently affected by age and gender. The hemodynamics of the carotid artery are strongly related to age also in healthy subjects. Pressure and flow velocity in the carotid artery can be separated into their reservoir and excess components. The new non-invasive technique based on diameter and velocity measurements could be relevant in clinical practice as a screening tool

A comparison between local wave speed in the carotid and femoral arteries in healthy humans: application of a new method

The wave speed (c) and the arrival time of reflected wave (Trw) in the common left carotid artery and common left femoral artery have been evaluated in 70 healthy subjects, aged 35-55 years with a non-invasive method. Wave speed and the arrival time of reflected waves were determined with InDU-loop and non-invasive wave intensity analysis (ndl) techniques, respectively. Diameter (D) was measured with ultrasound echo wall tracking and velocity (U) was obtained by ultrasonography. A statistical analysis has been carried out in order to establish a potential relation of c and Trw with gender and age in the study population. Subjects have been divided in two classes of age, one from 35 to 45 years and the other from 45 to 55 years. Results show that c and Trw in the femoral artery are higher than those in carotid, in both men and women (P < 0.001). Also, the distance of the reflection (L) site from the point of measurement is higher in the femoral than in the carotid artery. We did not find statistically significant differences between c, age or gender in femoral artery. However, c in the carotid artery increases with age (P < 0.05), but did not change between men and women. In this paper InDU-loop has been used for the first time to determine c and Trw in carotid and femoral arteries in a large population of healthy subjects

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection

BACKGROUND: Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID. OBJECTIVES: To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection. METHODS: 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls. RESULTS: Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months. CONCLUSION: CMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID. TRIAL REGISTRATION NUMBER: NCT04369807

CMR Native T1 Mapping Allows Differentiation of Reversible Versus Irreversible Myocardial Damage in ST-Segment–Elevation Myocardial Infarction

Background—CMR T1 mapping is a quantitative imaging technique allowing the assessment of myocardial injury early after ST-segment–elevation myocardial infarction. We sought to investigate the ability of acute native T1 mapping to differentiate reversible and irreversible myocardial injury and its predictive value for left ventricular remodeling. Methods and Results—Sixty ST-segment–elevation myocardial infarction patients underwent acute and 6-month 3T CMR, including cine, T2-weighted (T2W) imaging, native shortened modified look-locker inversion recovery T1 mapping, rest first pass perfusion, and late gadolinium enhancement. T1 cutoff values for oedematous versus necrotic myocardium were identified as 1251 ms and 1400 ms, respectively, with prediction accuracy of 96.7% (95% confidence interval, 82.8% to 99.9%). Using the proposed threshold of 1400 ms, the volume of irreversibly damaged tissue was in good agreement with the 6-month late gadolinium enhancement volume (r=0.99) and correlated strongly with the log area under the curve troponin (r=0.80) and strongly with 6-month ejection fraction (r=−0.73). Acute T1 values were a strong predictor of 6-month wall thickening compared with late gadolinium enhancement. Conclusions—Acute native shortened modified look-locker inversion recovery T1 mapping differentiates reversible and irreversible myocardial injury, and it is a strong predictor of left ventricular remodeling in ST-segment–elevation myocardial infarction. A single CMR acquisition of native T1 mapping could potentially represent a fast, safe, and accurate method for early stratification of acute patients in need of more aggressive treatment. Further confirmatory studies will be needed

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection

BackgroundLong COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID.ObjectivesTo investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection.Methods534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls.ResultsTechnical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months.ConclusionCMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID.Trial registration numberNCT04369807

Acute Microvascular Impairment Post-Reperfused STEMI Is Reversible and Has Additional Clinical Predictive Value: A CMR OxAMI Study

OBJECTIVES: This study sought to investigate the clinical utility and the predictive relevance of absolute rest myocardial blood flow (MBF) by cardiac magnetic resonance (CMR) in acute myocardial infarction. BACKGROUND: Microvascular obstruction (MVO) remains one of the worst prognostic factors in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Clinical trials have focused on cardioprotective strategies to maintain microvascular functionality, but there is a need for a noninvasive test to determine their efficacy. METHODS: A total of 64 STEMI patients post-primary percutaneous coronary intervention underwent 3-T CMR scans acutely and at 6 months (6M). The protocol included cine function, T2-weighted edema imaging, pre-contrast T1 mapping, rest first-pass perfusion, and late gadolinium enhancement imaging. Segmental MBF, corrected for rate pressure product (MBFcor), was quantified in remote, edematous, and infarcted myocardium. RESULTS: Acute MBFcor was significantly reduced in infarcted myocardium compared with remote MBF (MBFinfarct 0.76 ± 0.20 ml/min/g vs. MBFremote 1.02 ± 0.21 ml/min/g, p 45% at 6M increased by 1.38:1 [p 2 or index of myocardial resistance <40, acute MBF was associated with long-term functional recovery and was an independent predictor of infarct size reduction. CONCLUSIONS: Acute MBF by CMR could represent a novel quantitative imaging biomarker of microvascular reversibility, and it could be used to identify patients who may benefit from more intensive or novel therapie

Two-pool physical simulator of the inter-compartmental mass transfer during dialysis

A two-pool simulator of fluid and mass transfer among patient body compartments during hemodialysis (HD) was developed to characterize commercial dialyzers taking into account dynamic mass transfer effects. Materials and Methods: The two-pool simulator replicates intra- and extra-vascular compartments: the former by means of a rigid reservoir and a set of semi permeable hollow fibers, the latter by means of a compliant reservoir. The simulator design was optimized (in terms of fiber number, reservoir dimensions, etc.) by an ad hoc developed computational model. The set-up was then tested by simulating HD procedures with commercial filters. Blood samples were withdrawn from the simulator to evaluate urea and electrolytes (Na, Ca, Cl-, Mg, K) concentration. Intra- and extra-vascular volumes were directly monitored on the set-up. The experimental results were compared with clinically measured data. Results: All electrolytes (except K) and urea concentrations showed good agreement with the clinical data (maximum shift 11%). K concentration instead showed shifts of nearly 22%, probably due to the non replicated active mass transfer through the cellular membrane. Plasmatic volume profile showed good correlation with clinical patterns (0,24% shift) despite the tangled ultrafiltration rate setting on the simulator. Conclusions: The patient simulator satisfactorily reproduced electrolytes and volume profiles during a simulated HD thus showing reliability in testing dialyzers dynamic response. The device accuracy can be improved by reproducing active mass transfer through the cellular membrane as well as defining easier procedures to set ultrafiltration rate

Reservoir and reservoir-less pressure effects on arterial waves in the canine aorta

BACKGROUND:: A time-domain approach to couple the Windkessel effect and wave propagation has been recently introduced. The technique assumes that the measured pressure in the aorta (P) is the sum of a reservoir pressure (Pr), due to the storage of blood, and an excess pressure (Pe), due to the waves. Since the subtraction of Pr from P results in a smaller component of Pe, we hypothesized that using the reservoir-wave approach would produce smaller values of wave speed and intensities. Therefore, the aim of this study is to quantify the differences in wave speed and intensity using P, wave-only, and Pe, reservoir-wave techniques

Two-pool physical simulator of the inter-compartmental mass transfer during dialysis [in: ASAIO Abstracts for the 56th Annual Conference]

A two-pool simulator of fluid and mass transfer among patient body compartments during hemodialysis (HD) was developed to characterize commercial dialyzers taking into account dynamic mass transfer effects