Simulating impaired left ventricular-arterial coupling in aging and disease: a systematic review.

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers.

Non-invasive parameters of autonomic function using beat-to-beat cardiovascular variations and arterial stiffness in hypertensive individuals: a systematic review.

PURPOSE: Non-invasive, beat-to-beat variations in physiological indices provide an opportunity for more accessible assessment of autonomic dysfunction. The potential association between the changes in these parameters and arterial stiffness in hypertension remains poorly understood. This systematic review aims to investigate the association between non-invasive indicators of autonomic function based on beat-to-beat cardiovascular signals with arterial stiffness in individuals with hypertension. METHODS: Four electronic databases were searched from inception to June 2022. Studies that investigated non-invasive parameters of arterial stiffness and autonomic function using beat-to-beat cardiovascular signals over a period of > 5min were included. Study quality was assessed using the STROBE criteria. Two authors screened the titles, abstracts, and full texts independently. RESULTS: Nineteen studies met the inclusion criteria. A comprehensive overview of experimental design for assessing autonomic function in terms of baroreflex sensitivity and beat-to-beat cardiovascular variabilities, as well as arterial stiffness, was presented. Alterations in non-invasive indicators of autonomic function, which included baroreflex sensitivity, beat-to-beat cardiovascular variabilities and hemodynamic changes in response to autonomic challenges, as well as arterial stiffness, were identified in individuals with hypertension. A mixed result was found in terms of the association between non-invasive quantitative autonomic indices and arterial stiffness in hypertensive individuals. Nine out of 12 studies which quantified baroreflex sensitivity revealed a significant association with arterial stiffness parameters. Three studies estimated beat-to-beat heart rate variability and only one study reported a significant relationship with arterial stiffness indices. Three out of five studies which studied beat-to-beat blood pressure variability showed a significant association with arterial structural changes. One study revealed that hemodynamic changes in response to autonomic challenges were significantly correlated with arterial stiffness parameters. CONCLUSIONS: The current review demonstrated alteration in autonomic function, which encompasses both the sympathetic and parasympathetic modulation of sinus node function and vasomotor tone (derived from beat-to-beat cardiovascular signals) in hypertension, and a significant association between some of these parameters with arterial stiffness. By employing non-invasive measurements to monitor changes in autonomic function and arterial remodeling in individuals with hypertension, we would be able to enhance our ability to identify individuals at high risk of cardiovascular disease. Understanding the intricate relationships among these cardiovascular variability measures and arterial stiffness could contribute toward better individualized treatment for hypertension in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID: CRD42022336703. Date of registration: 12/06/2022.

Remodeling in Aortic Stenosis With Reduced and Preserved Ejection Fraction: Insight on Motion Abnormality Via 3D + Time Personalized LV Modeling in Cardiac MRI.

BACKGROUND: Increased afterload in aortic stenosis (AS) induces left ventricle (LV) remodeling to preserve a normal ejection fraction. This compensatory response can become maladaptive and manifest with motion abnormality. It is a clinical challenge to identify contractile and relaxation dysfunction during early subclinical stage to prevent irreversible deterioration. PURPOSE: To evaluate the changes of regional wall dynamics in 3D + time domain as remodeling progresses in AS. STUDY TYPE: Retrospective. POPULATION: A total of 31 AS patients with reduced and preserved ejection fraction (14 AS_rEF: 7 male, 66.5 [7.8] years old; 17 AS_pEF: 12 male, 67.0 [6.0] years old) and 15 healthy (6 male, 61.0 [7.0] years old). FIELD STRENGTH/SEQUENCE: 1.5 T Magnetic resonance imaging/steady state free precession and late-gadolinium enhancement sequences. ASSESSMENT: Individual LV models were reconstructed in 3D + time domain and motion metrics including wall thickening (TI), dyssynchrony index (DI), contraction rate (CR), and relaxation rate (RR) were automatically extracted and associated with the presence of scarring and remodeling. STATISTICAL TESTS: Shapiro-Wilk: data normality; Kruskal-Wallis: significant difference (P < 0.05); ICC and CV: variability; Mann-Whitney: effect size. RESULTS: AS_rEF group shows distinct deterioration of cardiac motions compared to AS_pEF and healthy groups (TIAS_rEF : 0.92 [0.85] mm, TIAS_pEF : 5.13 [1.99] mm, TIhealthy : 3.61 [1.09] mm, ES: 0.48-0.83; DIAS_rEF : 17.11 [7.89]%, DIAS_pEF : 6.39 [4.04]%, DIhealthy : 5.71 [1.87]%, ES: 0.32-0.85; CRAS_rEF : 8.69 [6.11] mm/second, CRAS_pEF : 16.48 [6.70] mm/second, CRhealthy : 10.82 [4.57] mm/second, ES: 0.29-0.60; RRAS_rEF : 8.45 [4.84] mm/second; RRAS_pEF : 13.49 [8.56] mm/second, RRhealthy : 9.31 [2.48] mm/second, ES: 0.14-0.43). The difference in the motion metrics between healthy and AS_pEF groups were insignificant (P-value = 0.16-0.72). AS_rEF group was dominated by eccentric hypertrophy (47.1%) with concomitant scarring. Conversely, AS_pEF group was dominated by concentric remodeling and hypertrophy (71.4%), which could demonstrate hyperkinesia with slight wall dyssynchrony than healthy. Dysfunction of LV mechanics corresponded to the presence of myocardial scarring (54.9% in AS), which reverted the compensatory mechanisms initiated and performed by LV remodeling. DATA CONCLUSION: The proposed 3D + time modeling technique may distinguish regional motion abnormalities between AS_pEF, AS_rEF, and healthy cohorts, aiding clinical diagnosis and monitoring of AS progression. Subclinical myocardial dysfunction is evident in early AS despite of normal EF. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Differences in Cardiovascular Regulation to Head-up Tilt between Healthy and Hypertensive Subjects.

To date there have only been limited studies exploring abnormal hemodynamic responses to head-up tilt tests (HUTs) in elderly, treated patients with hypertension. Cardiovascular regulation in response to HUT as well as upright hemodynamics may be altered when older hypertensive patients with antihypertensive treatments are studied. Hypertensive patients with and without receiving antihypertensive medication and above the age of 45 were recruited in this study. This study compared the cardiovascular responses to HUT and at rest between healthy and hypertensives using non-invasive hemodynamic measurements. Parameters such as systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke index (SI) and total peripheral resistance index (TPRI) were measured in 40 subjects (20 healthy and 20 hypertensives) for 10-min supine baseline, 10-min HUT at 70◦ and 6-min supine recovery. At rest and during HUT, SBP and TPRI were significantly higher in hypertensives together with a significantly smaller baseline SI. In response to HUT, both groups showed changes in hemodynamic parameters at differing degrees. During recovery, all parameters returned to the baseline range. Our findings indicated that hypertensive patients of older age being treated by antihypertensive drugs may have different cardiovascular changes in response to orthostatic stress.Clinical Relevance- This pilot study describes how cardiovascular regulation in response to postural change may behave differently in hypertensive elder patients taking antihypertensive drugs.

A Comparison of Haemodynamic Responses between Head-Up Tilt and Lower Body Negative Pressure.

Orthostatic intolerance (OI), a disorder of the autonomic nervous system, it is the development of symptoms when standing upright which are relieved when reclining. Head-up tilt (HUT) table test is a common test for assessing orthostatic tolerance. However, HUT is limited with low sensitivity and specificity. Another approach to stimulate the changing direction and value of the gravity field vector is the lower body negative pressure (LBNP) chamber. The aims of the study is to evaluate the physiological responses of healthy subjects on HUT and LBNP, and examine the relations of two tests. A total of 19 subjects were recruited. A validated wearable device, Sotera Visi Mobile was use to collect physiological signals simultaneously throughout the experiment procedures. Each subject went through a baseline supine rest, 70o of HUT test, another round of baseline supine rest, followed by activation of LBNP test. Three level of suction were applied, i.e. -30 mmHg, -40 mmHg, and -50 mmHg. In this pilot study, healthy subjects showed significantly increased of heart rate, and decreased of systolic blood pressure and diastolic blood pressure, in both HUT and LBNP tests. Although both tests are capable of stimulating a decreased blood volume in the central circulation, but the physiological responses behaved differently and shown only very week correlation. This suggesting that a combination of LBNP test with HUT test might work the best in orthostatic intolerance assessment.

Psychological status and physical performance are independently associated with autonomic function.

BACKGROUND: Falls among older adults have become a global concern. While previous studies have established associations between autonomic function indicator; heart rate variability (HRV) and blood pressure variability (BPV) with fall recurrence, as well as physical inactivity and psychological disorders as risk factors for falls, the influence of physical activity and psychological status on autonomic dysfunction observed among older fallers has not been adequately investigated. The aim of this study was to evaluate the relationship between psychological disorder and physical performance on the autonomic nervous system (ANS) in older fallers. We hypothesised that older fallers have poorer autonomic function, greater dependency on others and were associated with psychological disorders. Furthermore, we hypothesised that both physical performance and psychological status can contribute to the worsening of the autonomic function among the elderly. METHODS: In this cross-sectional survey, adults aged ≥ 60 years were recruited. Continuous non-invasive BP was monitored over 5 min of supine and 3 min of standing. Psychological status was assessed in terms of depression, anxiety, stress, and concern about falling, while functional status was measured using time-up-and-go, functional reach, handgrip and Lawton's Instrumental Activities of Daily Life (IADL) scale. RESULTS: A total of 62 participants were recruited consisting of 37 fallers and 25 non-fallers. Multivariate analysis revealed that Lawton IADL was independently associated with systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV) during both supine (SBPV: r2 = 0.080, p = 0.025; DBPV: r2 = 0.064, p = 0.046) and standing (SBPV: r2 = 0.112, p = 0.008; DBPV: r2 = 0.105, p = 0.011), while anxiety score was independently associated with SBPV and DBPV during standing (SBPV: r2 = 0.112, p = 0.009; DBPV: r2 = 0.105, p = 0.011) as compared to the other parameters. CONCLUSION: Our findings suggest that fallers had poorer ANS, greater dependence in IADLs, and were more anxious. IADL dependency and anxiety were the most predictive of autonomic dysfunction, and can be used in practice to identify poor autonomic function for the prevention of falls and cardiovascular diseases among older adults.

Association between mental illness and blood pressure variability: a systematic review.

BACKGROUND: Mental illness represents a major global burden of disease worldwide. It has been hypothesised that individuals with mental illness have greater blood pressure fluctuations that lead to increased cardiovascular risk and target organ damage. This systematic review aims to (i) investigate the association between mental illness and blood pressure variability (BPV) and (ii) describe methods of BPV measurements and analysis which may affect pattern and degree of variability. METHODS: Four electronic databases were searched from inception until 2020. The quality assessment was performed using STROBE criteria. Studies were included if they investigated BPV (including either frequency or time domain analysis) in individuals with mental illness (particularly anxiety/generalised anxiety disorder, depression/major depressive disorder, panic disorder and hostility) and without hypertension. Two authors independently screened titles, abstracts and full texts. A third author resolved any disagreements. RESULTS: Twelve studies met the inclusion criteria. Three studies measured short-term BPV, two measured long-term BPV and seven measured ultra-short-term BPV. All studies related to short-term BPV using ambulatory and home blood pressure monitoring found a higher BPV in individuals with depression or panic disorder. The two studies measuring long-term BPV were limited to the older population and found mixed results. Mental illness is significantly associated with an increased BPV in younger and middle-aged adults. All studies of ultra-short-term BPV using standard cardiac autonomic assessment; non-invasive continuous finger blood pressure and heart rate signals found significant association between BPV and mental illness. A mixed result related to degree of tilt during tilt assessment and between controlled and spontaneous breathing were observed in patients with psychological state. CONCLUSIONS: Current review found that people with mental illness is significantly associated with an increased BPV regardless of age. Since mental illness can contribute to the deterioration of autonomic function (HRV, BPV), early therapeutic intervention in mental illness may prevent diseases associated with autonomic dysregulation and reduce the likelihood of negative cardiac outcomes. Therefore, these findings may have important implications for patients' future physical health and well-being, highlighting the need for comprehensive cardiovascular risk reduction.

An integrated fluid-structure interaction and thrombosis model for type B aortic dissection.

False lumen thrombosis (FLT) in type B aortic dissection has been associated with the progression of dissection and treatment outcome. Existing computational models mostly assume rigid wall behavior which ignores the effect of flap motion on flow and thrombus formation within the FL. In this study, we have combined a fully coupled fluid-structure interaction (FSI) approach with a shear-driven thrombosis model described by a series of convection-diffusion reaction equations. The integrated FSI-thrombosis model has been applied to an idealized dissection geometry to investigate the interaction between vessel wall motion and growing thrombus. Our simulation results show that wall compliance and flap motion can influence the progression of FLT. The main difference between the rigid and FSI models is the continuous development of vortices near the tears caused by drastic flap motion up to 4.45 mm. Flap-induced high shear stress and shear rates around tears help to transport activated platelets further to the neighboring region, thus speeding up thrombus formation during the accelerated phase in the FSI models. Reducing flap mobility by increasing the Young's modulus of the flap slows down the thrombus growth. Compared to the rigid model, the predicted thrombus volume is 25% larger using the FSI-thrombosis model with a relatively mobile flap. Furthermore, our FSI-thrombosis model can capture the gradual effect of thrombus growth on the flow field, leading to flow obstruction in the FL, increased blood viscosity and reduced flap motion. This model is a step closer toward simulating realistic thrombus growth in aortic dissection, by taking into account the effect of intimal flap and vessel wall motion.

Comparison of diametric and volumetric changes in Stanford type B aortic dissection patients in assessing aortic remodeling post-stent graft treatment.

BACKGROUND: The study aims to analyze the correlation between the maximal diameter (both axial and orthogonal) and volume changes in the true (TL) and false lumens (FL) after stent-grafting for Stanford type B aortic dissection. METHOD: Computed tomography angiography was performed on 13 type B aortic dissection patients before and after procedure, and at 6 and 12 months follow-up. The lumens were divided into three regions: the stented area (Region 1), distal to the stent graft to the celiac artery (Region 2), and between the celiac artery and the iliac bifurcation (Region 3). Changes in aortic morphology were quantified by the increase or decrease of diametric and volumetric percentages from baseline measurements. RESULTS: At Region 1, the TL diameter and volume increased (pre-treatment: volume =51.4±41.9 mL, maximal axial diameter =22.4±6.8 mm, maximal orthogonal diameter =21.6±7.2 mm; follow-up: volume =130.7±69.2 mL, maximal axial diameter =40.1±8.1 mm, maximal orthogonal diameter =31.9+2.6 mm, P<0.05 for all comparisons), while FL decreased (pre-treatment: volume =129.6±150.5 mL; maximal axial diameter =43.0±15.8 mm; maximal orthogonal diameter =28.3±12.6 mm; follow-up: volume =66.6±95.0 mL, maximal axial diameter =24.5±19.9 mm, maximal orthogonal diameter =16.9±13.7, P<0.05 for all comparisons). Due to the uniformity in size throughout the vessel, high concordance was observed between diametric and volumetric measurements in the stented region with 93% and 92% between maximal axial diameter and volume for the true/false lumens, and 90% and 92% between maximal orthogonal diameter and volume for the true/false lumens. Large discrepancies were observed between the different measurement methods at regions distal to the stent graft, with up to 46% differences between maximal orthogonal diameter and volume. CONCLUSIONS: Volume measurement was shown to be a much more sensitive indicator in identifying lumen expansion/shrinkage at the distal stented region.

The role of regional myocardial topography post-myocardial infarction on infarct extension.

Infarct extension involves necrosis of healthy myocardium in the border zone (BZ), progressively enlarging the infarct zone (IZ) and recruiting the remote zone (RZ) into the BZ, eventually leading to heart failure. The mechanisms underlying infarct extension remain unclear, but myocyte stretching has been suggested as the most likely cause. Using human patient-specific left-ventricular (LV) numerical simulations established from cardiac magnetic resonance imaging (MRI) of myocardial infarction (MI) patients, the correlation between infarct extension and regional mechanics abnormality was investigated by analysing the fibre stress-strain loops (FSSLs). FSSL abnormality was characterised using the directional regional external work (DREW) index, which measures FSSL area and loop direction. Sensitivity studies were also performed to investigate the effect of infarct stiffness on regional myocardial mechanics and potential for infarct extension. We found that infarct extension was correlated to severely abnormal FSSL in the form of counter-clockwise loop at the RZ close to the infarct, as indicated by negative DREW values. In regions demonstrating negative DREW values, we observed substantial fibre stretching in the isovolumic relaxation (IVR) phase accompanied by a reduced rate of systolic shortening. Such stretching in IVR phase in part of the RZ was due to its inability to withstand the high LV pressure that was still present and possibly caused by regional myocardial stiffness inhomogeneity. Further analysis revealed that the occurrence of severely abnormal FSSL due to IVR fibre stretching near the RZ-BZ boundary was due to a large amount of surrounding infarcted tissue, or an excessively stiff IZ.

Effect of Vessel Tortuosity on Stress Concentration at the Distal Stent-Vessel Interface: Possible Link With New Entry Formation Through Biomechanical Simulation.

A computational approach is used to investigate potential risk factors for distal stent graft-induced new entry (dSINE) in aortic dissection (AD) patients. Patient-specific simulations were performed based on computed tomography images acquired from six AD patients (three dSINE and three non-dSINE) to analyze the correlation between anatomical characteristics and stress/strain distributions. Sensitivity analysis was carried out using idealized models to independently assess the effect of stent graft length, stent tortuosity and wedge apposition angle at the landing zone on key biomechanical variables. Mismatch of biomechanical properties between the stented and nonstented regions led to high stress at the distal stent graft-vessel interface in all patients, as well as shear strain in the neighboring region, which coincides with the location of tear formation. Stress was observed to increase with the increase of stent tortuosity (from 263 kPa at a tortuosity angle of 50 deg to 313 kPa at 30 deg). It was further amplified by stent graft landing at the inflection point of a curve. Malapposition of the stent graft led to an asymmetrical segment within the aorta, therefore changing the location and magnitude of the maximum von Mises stress substantially (up to +25.9% with a +25 deg change in the distal wedge apposition angle). In conclusion, stent tortuosity and wedge apposition angle serve as important risk predictors for dSINE formation in AD patients.

The study of myocardial ischemia-reperfusion treatment through computational modelling.

Reperfusion of the blood flow to ischemic myocardium is the standard treatment for patients suffering myocardial infarction. However, the reperfusion itself can also induce myocardial injury, in which the actual mechanism and its risk factors remain unclear. This work aims to study the mechanism of ischemia-reperfusion treatment using a three-dimensional (3D) oxygen diffusion model. An electrical model is then coupled to an oxygen model to identify the possible region of myocardial damage. Our findings show that the value of oxygen exceeds its optimum (>1.0) at the ischemic area during early reperfusion period. This complication was exacerbated in a longer ischemic period. While a longer reperfusion time causes a continuous excessive oxygen supply to the ischemic area throughout the reperfusion time. This work also suggests the use of less than 0.8 of initial oxygen concentration in the reperfusion treatment to prevent undesired upsurge at the early reperfusion period and further myocardial injury. We also found the region at risk for myocardial injury is confined in the ischemic vicinity revealed by its electrical conductivity impairment. Although there is a risk that reperfusion leads to myocardial injury for excessive oxygen accumulation, the reperfusion treatment is helpful in reducing the infarct size.

Phenotyping of hypertensive heart disease and hypertrophic cardiomyopathy using personalized 3D modelling and cardiac cine MRI.

Differential diagnosis of hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) is clinically challenging but important for treatment management. This study aims to phenotype HHD and HCM in 3D + time domain by using a multiparametric motion-corrected personalized modeling algorithm and cardiac magnetic resonance (CMR). 44 CMR data, including 12 healthy, 16 HHD and 16 HCM cases, were examined. Multiple CMR phenotype data consisting of geometric and dynamic variables were extracted globally and regionally from the models over a full cardiac cycle for comparison against healthy models and clinical reports. Statistical classifications were used to identify the distinctive characteristics and disease subtypes with overlapping functional data, providing insights into the challenges for differential diagnosis of both types of disease. While HCM is characterized by localized extreme hypertrophy of the LV, wall thickening/contraction/strain was found to be normal and in sync, though it was occasionally exaggerated at normotrophic/less severely hypertrophic regions during systole to preserve the overall ejection fraction (EF) and systolic functionality. Additionally, we observed that hypertrophy in HHD could also be localized, although at less extreme conditions (i.e. more concentric). While fibrosis occurs mostly in those HCM cases with aortic obstruction, only minority of HHD patients were found affected by fibrosis. We demonstrate that subgroups of HHD (i.e. preserved and reduced EF: HHDpEF & HHDrEF) have different 3D + time CMR characteristics. While HHDpEF has cardiac functions in normal range, dilation and heart failure are indicated in HHDrEF as reflected by low LV wall thickening/contraction/strain and synchrony, as well as much reduced EF.

The study of border zone formation in ischemic heart using electro-chemical coupled computational model.

Myocardial infarction (MI) is the most common cause of a heart failure, which occurs due to myocardial ischemia leading to left ventricular (LV) remodeling. LV remodeling particularly occurs at the ischemic area and the region surrounds it, known as the border zone. The role of the border zone in initiating LV remodeling process urges the investigation on the correlation between early border zone changes and remodeling outcome. Thus, this study aims to simulate a preliminary conceptual work of the border zone formation and evolution during onset of MI and its effect towards early LV remodeling processes by incorporating the oxygen concentration effect on the electrophysiology of an idealized three-dimensional LV through electro-chemical coupled mathematical model. The simulation result shows that the region of border zone, represented by the distribution of electrical conductivities, keeps expanding over time. Based on this result, the border zone is also proposed to consist of three sub-regions, namely mildly, moderately, and seriously impaired conductivity regions, which each region categorized depending on its electrical conductivities. This division could be used as a biomarker for classification of reversible and irreversible myocardial injury and will help to identify the different risks for the survival of patient. Larger ischemic size and complete occlusion of the coronary artery can be associated with an increased risk of developing irreversible injury, in particular if the reperfusion treatment is delayed. Increased irreversible injury area can be related with cardiovascular events and will further deteriorate the LV function over time.

Effect of intimal flap motion on flow in acute type B aortic dissection by using fluid-structure interaction.

A monolithic, fully coupled fluid-structure interaction (FSI) computational framework was developed to account for dissection flap motion in acute type B aortic dissection (TBAD). Analysis of results included wall deformation, pressure, flow, wall shear stress (WSS), von Mises stress and comparison of hemodynamics between rigid wall and FSI models. Our FSI model mimicked realistic wall deformation that resulted in maximum compression of the distal true lumen (TL) by 21.4%. The substantial movement of intimal flap mostly affected flow conditions in the false lumen (FL). Flap motion facilitated more flow entering the FL at peak systole, with the TL to FL flow split changing from 88:12 in the rigid model to 83:17 in the FSI model. There was more disturbed flow in the FL during systole (5.8% FSI vs 5.2% rigid) and diastole (13.5% FSI vs 9.8% rigid), via a λ2 -criterion. The flap-induced disturbed flow near the tears in the FSI model caused an increase of local WSS by up to 70.0% during diastole. This resulted in a significant reduction in the size of low time-averaged WSS (TAWSS) regions in the FL (113.11 cm2 FSI vs 177.44 cm2 rigid). Moreover, the FSI model predicted lower systolic pressure, higher diastolic pressure, and hence lower pulse pressure. Our results provided new insights into the possible impact of flap motion on flow in aortic dissections, which are particularly important when evaluating hemodynamics of acute TBAD. NOVELTY STATEMENT: Our monolithic fully coupled FSI computational framework is able to reproduce experimentally measured range of flap deformation in aortic dissection, thereby providing novel insights into the influence of physiological flap motion on the flow and pressure distributions. The drastic flap movement increases the flow resistance in the true lumen and causes more disturbed flow in the false lumen, as visualized through the λ2 criterion. The flap-induced luminal pressure is dampened, thereby affecting pressure measures, which may serve as potential prognostic indicators for late complications in acute uncomplicated TBAD patients.

Robust PPG motion artifact detection using a 1-D convolution neural network.

BACKGROUND AND OBJECTIVES: Continuous monitoring of physiological parameters such as photoplethysmography (PPG) has attracted increased interest due to advances in wearable sensors. However, PPG recordings are susceptible to various artifacts, and thus reducing the reliability of PPG-driven parameters, such as oxygen saturation, heart rate, blood pressure and respiration. This paper proposes a one-dimensional convolution neural network (1-D-CNN) to classify five-second PPG segments into clean or artifact-affected segments, avoiding data-dependent pulse segmentation techniques and heavy manual feature engineering. METHODS: Continuous raw PPG waveforms were blindly allocated into segments with an equal length (5s) without leveraging any pulse location information and were normalized with Z-score normalization methods. A 1-D-CNN was designed to automatically learn the intrinsic features of the PPG waveform, and perform the required classification. Several training hyperparameters (initial learning rate and gradient threshold) were varied to investigate the effect of these parameters on the performance of the network. Subsequently, this proposed network was trained and validated with 30 subjects, and then tested with eight subjects, with our local dataset. Moreover, two independent datasets downloaded from the PhysioNet MIMIC II database were used to evaluate the robustness of the proposed network. RESULTS: A 13 layer 1-D-CNN model was designed. Within our local study dataset evaluation, the proposed network achieved a testing accuracy of 94.9%. The classification accuracy of two independent datasets also achieved satisfactory accuracy of 93.8% and 86.7% respectively. Our model achieved a comparable performance with most reported works, with the potential to show good generalization as the proposed network was evaluated with multiple cohorts (overall accuracy of 94.5%). CONCLUSION: This paper demonstrated the feasibility and effectiveness of applying blind signal processing and deep learning techniques to PPG motion artifact detection, whereby manual feature thresholding was avoided and yet a high generalization ability was achieved.

The role of end-diastolic myocardial fibre stretch on infarct extension.

Myocardial infarct extension, a process involving the enlargement of infarct and border zone, leads to progressive degeneration of left ventricular (LV) function and eventually gives rise to heart failure. Despite carrying a high risk, the causation of infarct extension is still a subject of much speculation. In this study, patient-specific LV models were developed to investigate the correlation between infarct extension and impaired regional mechanics. Subsequently, sensitivity analysis was performed to examine the causal factors responsible for the impaired regional mechanics observed in regions surrounding the infarct and border zone. From our simulations, fibre strain, fibre stress and fibre stress-strain loop (FSSL) were the key biomechanical variables affected in these regions. Among these variables, only FSSL was correlated with infarct extension, as reflected in its work density dissipation (WDD) index value, with high WDD indices recorded at regions with infarct extension. Impaired FSSL is caused by inadequate contraction force generation during the isovolumic contraction and ejection phases. Our further analysis revealed that the inadequacy in contraction force generation is not necessarily due to impaired myocardial intrinsic contractility, but at least in part, due to inadequate muscle fibre stretch at end-diastole, which depresses the ability of myocardium to generate adequate contraction force in the subsequent systole (according to the Frank-Starling law). Moreover, an excessively stiff infarct may cause its neighbouring myocardium to be understretched at end-diastole, subsequently depressing the systolic contractile force of the neighbouring myocardium, which was found to be correlated with infarct extension.

Impact of myocardial infarction on intraventricular vortex and flow energetics assessed using computational simulations.

Flow energetics have been proposed as early indicators of progressive left ventricular (LV) functional impairment in patients with myocardial infarction (MI), but its correlation with individual MI parameters has not been fully explored. Using electro-fluid-structure interaction LV models, this study investigated the correlation between four MI parameters: infarct size, infarct multiplicity, regional enhancement of contractility at the viable myocardium area (RECVM), and LV mechanical dyssynchrony (LVMD) with intraventricular vortex and flow energetics. In LV with small infarcts, our results showed that infarct appearance amplified the energy dissipation index (DI), where substantial viscous energy loss was observed in areas with high flow velocity and near the infarct-vortex interface. The LV with small multiple infarcts and RECVM showed remarkable DI increment during systole and diastole. In correlation analysis, the systolic kinetic energy fluctuation index (E') was positively related to ejection fraction (EF) (R2  = 0.982) but negatively correlated with diastolic E' (R2  = 0.970). Diastolic E' was inversely correlated with vortex kinetic energy (R2  = 0.960) and vortex depth (R2  = 0.876). We showed an excessive systolic DI could differentiate infarcted LV with normal EF from healthy LV. Strong flow acceleration, LVMD, and vortex-infarct interactions were predominant factors that induced excessive DI in infarcted LVs. Instead of causing undesired flow turbulence, high systolic E' suggested the existence of energetic flow acceleration, while high diastolic E' implied an inefficient diastolic filling. Thus, systolic E' is not a suitable early indicator for progressive LV dysfunction in MI patients, while diastolic E' may be a useful index to indicate diastolic impairment in these patients.

Segmentation of left ventricle in late gadolinium enhanced MRI through 2D-4D registration for infarct localization in 3D patient-specific left ventricular model.

PURPOSE: To evaluate a 2D-4D registration-cum-segmentation framework for the delineation of left ventricle (LV) in late gadolinium enhanced (LGE) MRI and for the localization of infarcts in patient-specific 3D LV models. METHODS: A 3-step framework was proposed, consisting of: (1) 3D LV model reconstruction from motion-corrected 4D cine-MRI; (2) Registration of 2D LGE-MRI with 4D cine-MRI; (3) LV contour extraction from the intersection of LGE slices with the LV model. The framework was evaluated against cardiac MRI data from 27 patients scanned within 6 months after acute myocardial infarction. We compared the use of local Pearson's correlation (LPC) and normalized mutual information (NMI) as similarity measures for the registration. The use of 2 and 6 long-axis (LA) cine-MRI scans was also compared. The accuracy of the framework was evaluated using manual segmentation, and the interobserver variability of the scar volume derived from the segmented LV was determined using Bland-Altman analysis. RESULTS: LPC outperformed NMI as a similarity measure for the proposed framework using 6 LA scans, with Hausdorrf distance (HD) of 1.19 ± 0.53 mm versus 1.51 ± 2.01 mm (endocardial) and 1.21 ± 0.48 mm versus 1.46 ± 1.78 mm (epicardial), respectively. Segmentation using 2 LA scans was comparable to 6 LA scans with a HD of 1.23 ± 0.70 mm (endocardial) and 1.25 ± 0.74 mm (epicardial). The framework yielded a lower interobserver variability in scar volumes compared with manual segmentation. CONCLUSION: The framework showed high accuracy and robustness in delineating LV in LGE-MRI and allowed for bidirectional mapping of information between LGE- and cine-MRI scans, crucial in personalized model studies for treatment planning.

Assessing regional left ventricular thickening dysfunction and dyssynchrony via personalized modeling and 3D wall thickness measurements for acute myocardial infarction.

BACKGROUND: Existing clinical diagnostic and assessment methods could be improved to facilitate early detection and treatment of cardiac dysfunction associated with acute myocardial infarction (AMI) to reduce morbidity and mortality. PURPOSE: To develop 3D personalized left ventricular (LV) models and thickening assessment framework for assessing regional wall thickening dysfunction and dyssynchrony in AMI patients. STUDY TYPE: Retrospective study, diagnostic accuracy. SUBJECTS: Forty-four subjects consisting of 15 healthy subjects and 29 AMI patients. FIELD STRENGTH/SEQUENCE: 1.5T/steady-state free precession cine MRI scans; LGE MRI scans. ASSESSMENT: Quantitative thickening measurements across all cardiac phases were correlated and validated against clinical evaluation of infarct transmurality by an experienced cardiac radiologist based on the American Heart Association (AHA) 17-segment model. STATISTICAL TEST: Nonparametric 2-k related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's correlation coefficient. RESULTS: Healthy LV wall segments undergo significant wall thickening (P < 0.05) during ejection and have on average a thicker wall (8.73 ± 1.01 mm) compared with infarcted wall segments (2.86 ± 1.11 mm). Myocardium with thick infarct (ie, >50% transmurality) underwent remarkable wall thinning during contraction (thickening index [TI] = 1.46 ± 0.26 mm) as opposed to healthy myocardium (TI = 4.01 ± 1.04 mm). For AMI patients, LV that showed signs of thinning were found to be associated with a significantly higher percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index [DI] = 15.0 ± 5.0% vs. 7.5 ± 2.0%, P < 0.01). Also, a strong correlation was found between our TI and left ventricular ejection fraction (LVEF) (r = 0.892, P < 0.01), and moderate correlation between DI and LVEF (r = 0.494, P < 0.01). DATA CONCLUSION: The extracted regional wall thickening and DIs are shown to be strongly correlated with infarct severity, therefore suggestive of possible practical clinical utility. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1006-1019.