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1.
EuroIntervention ; 15(10): 902-911, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746755

RESUMO

AIMS: Correction of mitral and/or tricuspid regurgitation (MR, TR) frequently leads to poor outcomes in the days following intervention. We sought to understand how abrupt correction of MR and TR affects ventricular load and to investigate if gradual correction is beneficial. METHODS AND RESULTS: MR and TR were simulated using the CircAdapt cardiovascular system model with effective regurgitant orifice (ERO) areas of 0.5 cm2 and 0.7 cm2. Ventricular and atrial contractility reductions to 40% of normal and pulmonary hypertension were simulated. Abrupt and gradual ERO closure were simulated with homeostatic regulation of blood pressure and volume. Abrupt correction of MR increased left and right ventricular fibre stress by 40% and 15%, respectively, whereas TR correction increased left and right ventricular fibre stress by 26% and 19%, respectively. This spike was followed by a rapid drop in fibre stress. Myocardial dysfunction prolonged the spike but reduced its amplitude. Right ventricular fibre stress increased more with pulmonary hypertension and TR. Gradual correction demonstrated no spike in tissue load. CONCLUSIONS: Simulations demonstrated that abrupt ERO closure creates a transient increase in ventricular load that is prolonged by worsened myocardial condition and exacerbated by pulmonary hypertension. Gradual closure of the ERO abolishes this spike and merits clinical investigation.


Assuntos
Hipertensão Pulmonar , Insuficiência da Valva Mitral , Insuficiência da Valva Tricúspide , Átrios do Coração , Ventrículos do Coração , Humanos
2.
Front Physiol ; 10: 17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774598

RESUMO

Introduction: Timing of atrial, right (RV), and left ventricular (LV) stimulation in cardiac resynchronization therapy (CRT) is known to affect electrical activation and pump function of the LV. In this study, we used computer simulations, with input from animal experiments, to investigate the effect of varying pacing delays on both LV and RV electrical dyssynchrony and contractile function. Methods: A pacing protocol was performed in dogs with atrioventricular block (N = 6), using 100 different combinations of atrial (A)-LV and A-RV pacing delays. Regional LV and RV electrical activation times were measured using 112 electrodes and LV and RV pressures were measured with catheter-tip micromanometers. Contractile response to a pacing delay was defined as relative change of the maximum rate of LV and RV pressure rise (dP/dtmax) compared to RV pacing with an A-RV delay of 125 ms. The pacing protocol was simulated in the CircAdapt model of cardiovascular system dynamics, using the experimentally acquired electrical mapping data as input. Results: Ventricular electrical activation changed with changes in the amount of LV or RV pre-excitation. The resulting changes in dP/dtmax differed markedly between the LV and RV. Pacing the LV 10-50 ms before the RV led to the largest increases in LV dP/dtmax. In contrast, RV dP/dtmax was highest with RV pre-excitation and decreased up to 33% with LV pre-excitation. These opposite patterns of changes in RV and LV dP/dtmax were reproduced by the simulations. The simulations extended these observations by showing that changes in steady-state biventricular cardiac output differed from changes in both LV and RV dP/dtmax. The model allowed to explain the discrepant changes in dP/dtmax and cardiac output by coupling between atria and ventricles as well as between the ventricles. Conclusion: The LV and the RV respond in a opposite manner to variation in the amount of LV or RV pre-excitation. Computer simulations capture LV and RV behavior during pacing delay variation and may be used in the design of new CRT optimization studies.

3.
J Am Heart Assoc ; 8(2): e010903, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30651018

RESUMO

Background The relative impact of right ventricular ( RV ) electromechanical dyssynchrony versus pulmonary regurgitation ( PR ) on exercise capacity and RV function after tetralogy of Fallot repair is unknown. We aimed to delineate the relative effects of these factors on RV function and exercise capacity. Methods and Results We retrospectively analyzed 81 children with tetralogy of Fallot repair using multivariable regression. Predictor parameters were electrocardiographic QRS duration reflecting electromechanical dyssynchrony and PR severity by cardiac magnetic resonance. The outcome parameters were exercise capacity (percentage predicted peak oxygen consumption) and cardiac magnetic resonance ejection fraction (RV ejection fraction). To understand the relative effects of RV dyssynchrony versus PR on exercise capacity and RV function, virtual patient simulations were performed using a closed-loop cardiovascular system model (CircAdapt), covering a wide spectrum of disease severity. Eighty-one patients with tetralogy of Fallot repair (median [interquartile range { IQR} ] age, 14.48 [11.55-15.91] years) were analyzed. All had prolonged QRS duration (median [IQR], 144 [123-152] ms), at least moderate PR (median [IQR], 40% [29%-48%]), reduced exercise capacity (median [IQR], 79% [68%-92%] predicted peak oxygen consumption), and reduced RV ejection fraction (median [IQR], 48% [44%-52%]). Longer QRS duration, more than PR , was associated with lower oxygen consumption and lower RV ejection fraction. In a multivariable regression analysis, oxygen consumption decreased with both increasing QRS duration and PR severity. CircAdapt modeling showed that RV dyssynchrony exerts a stronger limiting effect on exercise capacity and on RV ejection fraction than does PR , regardless of contractile function. Conclusions In both patient data and computer simulations, RV dyssynchrony, more than PR , appears to be associated with reduced exercise capacity and RV systolic dysfunction in patients after TOF repair.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Tolerância ao Exercício/fisiologia , Ventrículos do Coração/fisiopatologia , Complicações Pós-Operatórias , Insuficiência da Valva Pulmonar/fisiopatologia , Tetralogia de Fallot/cirurgia , Disfunção Ventricular Direita/etiologia , Adolescente , Criança , Estudos Transversais , Progressão da Doença , Eletrocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Consumo de Oxigênio , Prognóstico , Insuficiência da Valva Pulmonar/diagnóstico , Insuficiência da Valva Pulmonar/etiologia , Estudos Retrospectivos , Volume Sistólico , Tetralogia de Fallot/diagnóstico , Tetralogia de Fallot/fisiopatologia , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/fisiopatologia
4.
JACC Cardiovasc Imaging ; 12(9): 1741-1752, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30219394

RESUMO

OBJECTIVES: In this study, the authors tested the hypotheses that the systolic stretch index (SSI) developed by computer modeling and applied using echocardiographic strain imaging may characterize the electromechanical substrate predictive of outcome following cardiac resynchronization therapy (CRT). They included patients with QRS width 120 to 149 ms or non-left bundle branch block (LBBB), where clinical uncertainty for CRT exists. They further tested the hypothesis that global longitudinal strain (GLS) has additional prognostic value. BACKGROUND: Response to CRT is variable. Guidelines favor patient selection by electrocardiographic LBBB with QRS width ≥150 ms. METHODS: The authors studied 442 patients enrolled in the Adaptive CRT 94-site randomized trial with New York Heart Association functional class III-IV heart failure, ejection fraction ≤35%, and QRS ≥120 ms. A novel computer program semiautomatically calculated the SSI from strain curves as the sum of posterolateral prestretch percent before aortic valve opening and the septal rebound stretch percent during ejection. The primary endpoint was hospitalization for heart failure (HF) or death, and the secondary endpoint was death over 2 years after CRT. RESULTS: In all patients, high longitudinal SSI (≥ group median of 3.1%) was significantly associated with freedom from the primary endpoint of HF hospitalization or death (hazard ratio [HR] for low SSI: 2.17; 95% confidence interval [CI]: 1.45 to 3.24, p < 0.001) and secondary endpoint of death (HR for low SSI: 4.06; 95% CI: 1.95 to 8.45, p < 0.001). Among the 203 patients with QRS 120 to 149 ms or non-LBBB, those with high longitudinal SSI (≥ group median of 2.6%) had significantly fewer HF hospitalizations or deaths (HR for low SSI: 2.08; 95% CI: 1.27 to 3.41, p = 0.004) and longer survival (HR for low SSI: 5.08; 95% CI: 1.94 to 13.31, p < 0.001), similar to patients with LBBB ≥150 ms. SSI by circumferential strain had similar associations with clinical outcomes, and GLS was additive to SSI in predicting clinical events (p = 0.001). CONCLUSIONS: Systolic stretch by strain imaging characterized the myocardial substrate associated with favorable CRT response, including in the important patient subgroup with QRS width 120 to 149 ms or non-LBBB. GLS had additive prognostic value.

5.
J Am Chem Soc ; 141(2): 1027-1034, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30582804

RESUMO

Melt quenched metal-organic framework (MOF) glasses define a new category of glass, distinct from metallic, organic, and inorganic glasses, owing to the dominant role of metal-ligand coordination bonding. The mechanical properties of glasses in general are important given their application in protective coatings and display technologies, though little is known about MOF glasses in this respect. The experimental elucidation of key properties such as their scratch resistance has been limited by the lack of processing methodologies capable of producing bulk glass samples. Here, nanoindentation was used to investigate the Young's modulus and hardness of four melt-quenched glasses formed from zeolitic imidazolate frameworks (ZIF): agZIF-4, agZIF-62, agZIF-76, and agZIF-76-mbIm. The creep resistance of the melt-quenched glasses was studied via strain-rate jump (SRJ) tests and through constant load and hold (CLH) indentation creep experiments. Values for the strain-rate sensitivity were found to be close to those for other glassy polymers and Se-rich GeSe chalcogenide glasses. Vacuum hot-pressing of agZIF-62 resulted in an inhomogeneous bulk sample containing the glass and amorphous non-melt-quenched aZIF-62. Remelting and annealing, however, resulted in the fabrication of a transparent, bubble-free bulk specimen, which allowed the first scratch testing experiments to be performed on an MOF glass.

6.
Biomed Eng Online ; 17(1): 182, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518387

RESUMO

BACKGROUND: Myocardial deformation measured by strain is used to detect electro-mechanical abnormalities in cardiac tissue. Estimation of myocardial properties from regional strain patterns when multiple pathologies are present is therefore a promising application of computer modelling. However, if different tissue properties lead to indistinguishable strain patterns ('degeneracy'), the applicability of any such method will be limited. We investigated whether estimation of local activation time (AT) and contractility from myocardial strain patterns is theoretically possible. METHODS: For four different global cardiac pathologies local myocardial strain patterns for 1025 combinations of AT and contractility were simulated with a computational model (CircAdapt). For each strain pattern, a cohort of similar patterns was found within estimated measurement error using the sum of least-squared differences. Cohort members came from (1) the same pathology only, and (2) all four pathologies. Uncertainty was calculated as accuracy and precision of cohort members in parameter space. Connectedness within the cohorts was also studied. RESULTS: We found that cohorts drawn from one pathology had parameters with adjacent values although their distribution was neither constant nor symmetrical. In comparison cohorts drawn from four pathologies had disconnected components with drastically different parameter values and accuracy and precision values up to three times higher. CONCLUSIONS: Global pathology must be known when extracting AT and contractility from strain patterns, otherwise degeneracy occurs causing unacceptable uncertainty in derived parameters.


Assuntos
Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Modelos Cardiovasculares , Contração Miocárdica , Miocárdio/patologia , Estresse Mecânico , Fenômenos Biomecânicos , Incerteza
7.
Circ Arrhythm Electrophysiol ; 11(4): e005647, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29654125

RESUMO

BACKGROUND: The predictive value of interventricular versus intraventricular dyssynchrony for response to cardiac resynchronization therapy (CRT) remains unclear. We investigated the relative importance of both ventricular electrical substrate components for left ventricular (LV) hemodynamic function. METHODS AND RESULTS: First, we used the cardiovascular computational model CircAdapt to characterize the isolated effect of intrinsic interventricular and intraventricular activation on CRT response (ΔLVdP/dtmax). Simulated ΔLVdP/dtmax (range: 1.3%-26.5%) increased considerably with increasing interventricular dyssynchrony. In contrast, the isolated effect of intraventricular dyssynchrony in either the LV or right ventricle was limited (ΔLVdP/dtmax range: 12.3%-18.3% and 14.1%-15.7%, respectively). Effects of activation during biventricular pacing on ΔLVdP/dtmax were small. Second, electrocardiographic imaging-derived activation characteristics of 51 CRT candidates were used to personalize ventricular activation in CircAdapt. The individualized models were subsequently used to assess the accuracy of ΔLVdP/dtmax prediction based on the electrical data. The model-predicted ΔLVdP/dtmax was close to the actual value in patients with left bundle branch block (measured-simulated: 2.7±9.0%) when only intrinsic interventricular dyssynchrony was personalized. Among patients without left bundle branch block, ΔLVdP/dtmax was systematically overpredicted by CircAdapt (measured-simulated: 9.2±7.1%). Adding intraventricular activation to the model did not improve the accuracy of the response prediction. CONCLUSIONS: Computer simulations revealed that intrinsic interventricular dyssynchrony is the dominant component of the electrical substrate driving the response to CRT. Intrinsic intraventricular dyssynchrony and any dyssynchrony during biventricular pacing play a minor role in this respect. This may facilitate patient-specific modeling for prediction of CRT response. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01270646.


Assuntos
Terapia de Ressincronização Cardíaca , Bloqueio Cardíaco/terapia , Insuficiência Cardíaca/terapia , Hemodinâmica , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Disfunção Ventricular Esquerda/terapia , Função Ventricular Esquerda , Potenciais de Ação , Eletrocardiografia , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Direita , Pressão Ventricular
8.
Cardiovasc Res ; 113(12): 1486-1498, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957534

RESUMO

Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future.


Assuntos
Técnicas de Imagem Cardíaca , Hipertrofia Ventricular Direita/diagnóstico por imagem , Contração Miocárdica , Modelagem Computacional Específica para o Paciente , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita , Animais , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Modelos Cardiovasculares , Valor Preditivo dos Testes , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
9.
J Am Soc Echocardiogr ; 30(10): 1012-1020.e2, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28801203

RESUMO

BACKGROUND: Pronounced echocardiographically measured mechanical dyssynchrony is a positive predictor of response to cardiac resynchronization therapy (CRT), whereas right ventricular (RV) dysfunction is a negative predictor. The aim of this study was to investigate how RV dysfunction influences the association between mechanical dyssynchrony and left ventricular (LV) volumetric remodeling following CRT. METHODS: One hundred twenty-two CRT candidates (mean LV ejection fraction, 19 ± 6%; mean QRS width, 168 ± 21 msec) were prospectively enrolled and underwent echocardiography before and 6 months after CRT. Volumetric remodeling was defined as percentage reduction in LV end-systolic volume. RV dysfunction was defined as RV fractional area change < 35%. Mechanical dyssynchrony was assessed as time to peak strain between the septum and LV lateral wall, interventricular mechanical delay, and septal systolic rebound stretch. Simulations of heart failure with an LV conduction delay in the CircAdapt computer model were used to investigate how LV and RV myocardial contractility influence LV dyssynchrony and acute CRT response. RESULTS: In the entire patient cohort, higher baseline septal systolic rebound stretch, time to peak strain between the septum and LV lateral wall, and interventricular mechanical delay were all associated with LV volumetric remodeling in univariate analysis (R = 0.599, R = 0.421, and R = 0.410, respectively, P < .01 for all). The association between septal systolic rebound stretch and LV volumetric remodeling was even stronger in patients without RV dysfunction (R = 0.648, P < .01). However, none of the mechanical dyssynchrony parameters were associated with LV remodeling in the RV dysfunction subgroup. The computer simulations showed that low RV contractility reduced CRT response but hardly affected mechanical dyssynchrony. In contrast, LV contractility changes had congruent effects on mechanical dyssynchrony and CRT response. CONCLUSIONS: Mechanical dyssynchrony parameters do not reflect the negative impact of reduced RV contractility on CRT response. Echocardiographic prediction of CRT response should therefore include parameters of mechanical dyssynchrony and RV function.


Assuntos
Terapia de Ressincronização Cardíaca , Simulação por Computador , Ecocardiografia/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita , Idoso , Terapia de Ressincronização Cardíaca/métodos , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade
10.
J Am Chem Soc ; 139(10): 3706-3715, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28191967

RESUMO

Size-dependent phenomena at the nanoscale influence many applications, notably in the science of heterogeneous catalysis. In cobalt-based Fischer-Tropsch synthesis (FTS), the size of Co nanoparticles (NPs) dictates to a high degree catalyst's performance in terms of activity, selectivity, and stability. Here, a highly dispersed Re/Co/γ-Al2O3 catalyst with high Co surface area per gram of catalyst was exposed to industrially relevant FTS conditions and monitored in situ by synchrotron X-ray radiation. X-ray absorption near-edge structure spectra were obtained on the cobalt K edge and Re L3 edge of the working catalyst. The experimental results demonstrate development of tetrahedrally coordinated Co2+ forming at the expense of metallic Co(0). The structure of the oxide resembles CoAl2O4 and appears at the onset (first 5-10 h) of the reaction. Reoxidation of Co(0) is more pronounced close to the outlet of the reactor, where higher pH2O is anticipated. The state of the Re promoter does not change during the FT process. We propose that reoxidation of small Co NPs is followed by spreading of Co oxide that leads to the formation of CoxAlyOz phases. Hence, in order to avoid an irreversible loss of the active phase during process start-up, catalyst design should be restricted to Co NPs larger than 5.3 nm.

11.
Am J Physiol Heart Circ Physiol ; 312(4): H691-H700, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28039201

RESUMO

Rapid leftward septal motion (RLSM) during early left ventricular (LV) diastole is observed in patients with pulmonary arterial hypertension (PAH). RLSM exacerbates right ventricular (RV) systolic dysfunction and impairs LV filling. Increased RV wall tension caused by increased RV afterload has been suggested to cause interventricular relaxation dyssynchrony and RLSM in PAH. Simulations using the CircAdapt computational model were used to unravel the mechanism underlying RLSM by mechanistically linking myocardial tissue and pump function. Simulations of healthy circulation and mild, moderate, and severe PAH were performed. We also assessed the effects on RLSM when PAH coexists with RV or LV contractile dysfunction. Our results showed prolonged RV shortening in PAH causing interventricular relaxation dyssynchrony and RLSM. RLSM was observed in both moderate and severe PAH. A negative transseptal pressure gradient only occurred in severe PAH, demonstrating that negative pressure gradient does not entirely explain septal motion abnormalities. PAH coexisting with RV contractile dysfunction exacerbated both interventricular relaxation dyssynchrony and RLSM. LV contractile dysfunction reduced both interventricular relaxation dyssynchrony and RLSM. In conclusion, dyssynchrony in ventricular relaxation causes RLSM in PAH. Onset of RLSM in patients with PAH appears to indicate a worsening in RV function and hence can be used as a sign of RV failure. However, altered RLSM does not necessarily imply an altered RV afterload, but it can also indicate altered interplay of RV and LV contractile function. Reduction of RLSM can result from either improved RV function or a deterioration of LV function.NEW & NOTEWORTHY A novel approach describes the mechanism underlying abnormal septal dynamics in pulmonary arterial hypertension. Change in motion is not uniquely induced by altered right ventricular afterload, but also by altered ventricular relaxation dyssynchrony. Extension or change in motion is a marker reflecting interplay between right and left ventricular contractility.


Assuntos
Septos Cardíacos/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Biomarcadores , Simulação por Computador , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/complicações , Contração Miocárdica , Miocárdio/metabolismo , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Disfunção Ventricular Direita/etiologia , Função Ventricular
12.
J Am Coll Cardiol ; 68(20): 2185-2197, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27855808

RESUMO

BACKGROUND: Previous studies suggested that electrical abnormalities precede overt structural disease in arrhythmogenic right ventricular cardiomyopathy (ARVC). Abnormal RV deformation has been reported in early ARVC without structural abnormalities. The pathophysiological mechanisms underlying these abnormalities remain unknown. OBJECTIVES: The authors used imaging and computer simulation to differentiate electrical from mechanical tissue substrates among ARVC clinical stages. METHODS: ARVC desmosomal mutation carriers (n = 84) were evaluated by electrocardiography (ECG), Holter monitoring, late-enhancement cardiac magnetic resonance imaging, and echocardiographic RV deformation imaging. Subjects were categorized based on the presence of 2010 International Task Force criteria: 1) subclinical stage (n = 21); 2) electrical stage (n = 15); and 3) structural stage (n = 48). Late enhancement was not present in any subclinical or electrical stage subjects. RESULTS: Three distinctive characteristic RV longitudinal deformation patterns were identified: type I: normal deformation (n = 12); type II: delayed onset of shortening, reduced systolic peak strain, and mild post-systolic shortening (n = 35); and type III: systolic stretching with large post-systolic shortening (n = 37). A majority (69%) of structural staged mutation carriers were type III, whereas a large proportion of both electrical and subclinical stage subjects (67% and 48%, respectively) were type II. Computer simulations demonstrated that the type II pattern can be explained by a combination of reduced contractility and mildly increased passive myocardial stiffness. This evolved into type III by aggravating both mechanical substrates. Electrical activation delay alone explained none of the patterns. CONCLUSIONS: Different ARVC stages were characterized by distinct RV deformation patterns, all of which could be reproduced by simulating different degrees of mechanical substrates. Subclinical and electrical staged ARVC subjects already showed signs of local mechanical abnormalities. Our novel approach could lead to earlier disease detection and, thereby, influence current definitions of electrical and subclinical ARVC stages.


Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico , Simulação por Computador , Eletrocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Contração Miocárdica/fisiologia , Adulto , Displasia Arritmogênica Ventricular Direita/classificação , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Ecocardiografia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Estudos Retrospectivos
13.
ChemSusChem ; 9(21): 3093-3101, 2016 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-27754604

RESUMO

The specific energy of a supercapacitor (SC) with an ionic liquid (IL)-based electrolyte is larger than that using an aqueous electrolyte owing to the wide operating voltage window provided by the IL. However, the wide-scale application of high-energy SCs using ILs is limited owing to a serious reduction of the energy with increasing power. The introduction of macropores to the porous material can mitigate the reduction in the gravimetric capacitance at high rates, but this lowers the volumetric capacitance. Synthetic polymers can be used to obtain macroporous frameworks with high apparent densities, but the preservation of the frameworks during activation is challenging. To simultaneously achieve high gravimetric capacitance, volumetric capacitance, and rate capability, a systematic strategy was used to synthesize a densely knitted carbon framework with a hierarchical pore structure by using a polymer. The energy of the SC using the hierarchically porous carbon was 160 Wh kg-1 and 85 Wh L-1 on an active material base at a power of 100 W kg-1 in an IL electrolyte, and 60 % of the energy was still retained at a power larger than 5000 W kg-1 . To illustrate, a full-packaged SC with the material could store/release energy comparable to a Ni-metal hydride battery (gravimetrically) and one order of magnitude higher than a commercial carbon-based SC (volumetrically), within one minute.


Assuntos
Capacitância Elétrica , Fontes de Energia Elétrica , Líquidos Iônicos/química , Eletrólitos/química , Polímeros/química , Porosidade
14.
J Am Soc Echocardiogr ; 29(11): 1122-1130.e4, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27638236

RESUMO

BACKGROUND: Assessment of aortic regurgitation (AR) severity is often based on Doppler echocardiographic imaging. Hemodynamic responses to AR are influenced by the interplay among cardiovascular properties, including left ventricular (LV) and aortic tissue properties, that cannot be measured directly. The aim of this study was to investigate how both echocardiographic measures of AR severity and the hemodynamic consequences of AR are influenced by LV and aortic stiffness. METHODS: AR was simulated using the CircAdapt computational model of the human cardiovascular system. Simulations were performed with normal LV and aortic stiffness, high LV stiffness, high aortic stiffness, and high LV and aortic stiffness. For each configuration of levels of stiffness, four AR severity grades were simulated by setting the effective regurgitant orifice area (ROA) of the aortic valve at 0, 0.05, 0.25, and 0.6 cm2, representing no, mild, moderate, and severe AR, respectively. The regurgitant volume, regurgitant fraction (RF), and pressure half-time (PHT) were computed for each simulation giving an AR severity score (mild, moderate, or severe). Mean left atrial pressure was also calculated. RESULTS: Increasing ROA resulted in faster decay of diastolic flow velocity and larger regurgitant blood flow across the aortic valve. This caused shorter PHT and larger regurgitant volume and RF, all indicating higher AR severity. Increasing aortic stiffness resulted in a larger decline in diastolic aortic pressure, whereas increasing LV stiffness resulted in a larger rise in diastolic LV pressure. Hence, increasing LV and/or aortic stiffness led to faster decay of the transvalvular pressure gradient and, therefore, to faster decay of diastolic flow velocity across the aortic valve compared with normal stiffness with the same ROA. This faster decay led, on one hand, to a shorter PHT, indicating higher severity scores, and, on the other hand, to a lower RF, as less regurgitant blood volume traveled into the left ventricle, indicating lower severity scores. AR severity scores reflected mean left atrial pressure poorly when variations in tissue properties were present. CONCLUSIONS: Simulating altered AR hemodynamics caused by variations in cardiovascular tissue properties led to inconsistent severity scores when evaluating the severity using RF, regurgitant volume, and PHT. In this situation, pulmonary congestion is poorly reflected by AR severity as quantified by ROA, RF, and PHT. Cardiac and aortic tissue properties should therefore be taken into account to improve clinical assessment of AR severity.


Assuntos
Aorta/fisiopatologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Ecocardiografia Doppler/métodos , Ventrículos do Coração/fisiopatologia , Modelos Cardiovasculares , Aorta/diagnóstico por imagem , Artefatos , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Ventrículos do Coração/diagnóstico por imagem , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Rigidez Vascular
15.
Am J Physiol Heart Circ Physiol ; 310(3): H394-403, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26721864

RESUMO

Abnormal left-right motion of the interventricular septum in early systole, known as septal flash (SF), is frequently observed in patients with left bundle branch block (LBBB). Transseptal pressure gradient and early active septal contraction have been proposed as explanations for SF. Similarities in timing (early systole) and location (septum) suggest that SF may be related to septal systolic rebound stretch (SRSsept). We aimed to clarify the mechanisms generating SF and SRSsept. The CircAdapt computer model was used to isolate the effects of timing of activation of the left ventricular free wall (LVFW), right ventricular free wall (RVFW), and septum on SF and SRSsept. LVFW and septal activation times were varied by ±80 ms relative to RVFW activation time. M-mode-derived wall motions and septal strains were computed and used to quantify SF and SRSsept, respectively. SF depended on early activation of the RVFW relative to the LVFW. SF and SRSsept occurred in LBBB-like simulations and against a rising transseptal pressure gradient. When the septum was activated before both LVFW and RVFW, no SF occurred despite the presence of SRSsept. Computer simulations therefore indicate that SF and SRSsept have different underlying mechanisms, even though both can occur in LBBB. The mechanism of leftward motion during SF is early RVFW contraction pulling on and straightening the septum when unopposed by the LVFW. SRSsept is caused by late LVFW contraction following early contraction of the septum. Changes in transseptal pressure gradient are not the main cause of SF in LBBB.


Assuntos
Bloqueio de Ramo/fisiopatologia , Contração Miocárdica/fisiologia , Septo Interventricular/fisiopatologia , Simulação por Computador , Ecocardiografia , Humanos , Modelos Cardiovasculares , Sístole
17.
Circ Cardiovasc Imaging ; 8(9): e003744, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26338877

RESUMO

BACKGROUND: Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates. METHODS AND RESULTS: First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35%) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7% had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95% confidence interval, 0.19-0.53; P<0.001) and less deaths, transplants, or LV assist devices (hazard ratio, 0.28; 95% confidence interval, 0.15-0.55; P<0.001). Furthermore, in a subgroup of 113 patients with intermediate electrocardiographic criteria (QRS duration of 120-149 ms or non-left bundle branch block), SSI≥9.7% was independently associated with significantly less heart failure hospitalizations or deaths (hazard ratio, 0.41; 95% confidence interval, 0.23-0.79; P=0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95% confidence interval, 0.12-0.60; P=0.001). CONCLUSIONS: Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone.


Assuntos
Terapia de Ressincronização Cardíaca , Simulação por Computador , Ecocardiografia/métodos , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Idoso , Eletrocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento
18.
PLoS Comput Biol ; 11(7): e1004284, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26204520

RESUMO

Cardiac electrical asynchrony occurs as a result of cardiac pacing or conduction disorders such as left bundle-branch block (LBBB). Electrically asynchronous activation causes myocardial contraction heterogeneity that can be detrimental for cardiac function. Computational models provide a tool for understanding pathological consequences of dyssynchronous contraction. Simulations of mechanical dyssynchrony within the heart are typically performed using the finite element method, whose computational intensity may present an obstacle to clinical deployment of patient-specific models. We present an alternative based on the CircAdapt lumped-parameter model of the heart and circulatory system, called the MultiPatch module. Cardiac walls are subdivided into an arbitrary number of patches of homogeneous tissue. Tissue properties and activation time can differ between patches. All patches within a wall share a common wall tension and curvature. Consequently, spatial location within the wall is not required to calculate deformation in a patch. We test the hypothesis that activation time is more important than tissue location for determining mechanical deformation in asynchronous hearts. We perform simulations representing an experimental study of myocardial deformation induced by ventricular pacing, and a patient with LBBB and heart failure using endocardial recordings of electrical activation, wall volumes, and end-diastolic volumes. Direct comparison between simulated and experimental strain patterns shows both qualitative and quantitative agreement between model fibre strain and experimental circumferential strain in terms of shortening and rebound stretch during ejection. Local myofibre strain in the patient simulation shows qualitative agreement with circumferential strain patterns observed in the patient using tagged MRI. We conclude that the MultiPatch module produces realistic regional deformation patterns in the asynchronous heart and that activation time is more important than tissue location within a wall for determining myocardial deformation. The CircAdapt model is therefore capable of fast and realistic simulations of dyssynchronous myocardial deformation embedded within the closed-loop cardiovascular system.


Assuntos
Bloqueio de Ramo/fisiopatologia , Acoplamento Excitação-Contração , Sistema de Condução Cardíaco/fisiopatologia , Modelos Cardiovasculares , Contração Miocárdica , Disfunção Ventricular Esquerda/fisiopatologia , Algoritmos , Animais , Bloqueio de Ramo/complicações , Simulação por Computador , Humanos , Software , Disfunção Ventricular Esquerda/etiologia
19.
J Appl Phycol ; 27(2): 777-786, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25866446

RESUMO

Diatoms are an ecologically successful group within the phytoplankton, and their special feature is a biofabricated silica cell encasement called a frustule. These frustules attract interest in material technology, and one potential application is to use them in solar cell technology. The silica frustule with its nanoscaled pattern is interesting per se, but the utility is enhanced if we succeed in incorporating other elements. Titanium is an interesting element because its oxide is a semi-conductor with a high band gap. However, doping with relevant elements through bioincorporation is challenging, and it is necessary to understand the biology involved in element uptake and incorporation. Here we present data on bioincorporation of Ti into the silica frustules of the pennate diatom Pinnularia sp. (Ehrenberg) and show that the distribution of the incorporated Ti is inhomogeneous both between and within valves. More than a tenfold increase of Ti in newly synthesised valves was achieved, and increased Ti around the pores was confirmed by both EDS and EELS analyses. HAADF STEM spectroscopy revealed a grainy surface with amorphous silica particles of 4 to 5 nm in size. These observations are explained by what is known from the physico-chemical processes involved in biosilification and frustule formation, looking into it from a biological point of view.

20.
J Theor Biol ; 365: 325-36, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25451525

RESUMO

Variability in the action potential of isolated myocytes and tissue samples is observed in experimental studies. Variability is manifested as both differences in the action potential (AP) morphology between cells (extrinsic variability), and also 'intrinsic' or beat-to-beat variability of repolarization (BVR) in the AP duration of each cell. We studied the relative contributions of experimentally recorded intrinsic and extrinsic variability to dispersion of repolarization in tissue. We developed four cell-specific parameterizations of a phenomenological stochastic differential equation AP model exhibiting intrinsic variability using APs recorded from isolated guinea pig ventricular myocytes exhibiting BVR. We performed simulations in tissue using the four different model parameterizations in the presence and the absence of both intrinsic and extrinsic variability. We altered the coupling of the tissue to determine how inter-cellular coupling affected the dispersion of the AP duration in tissue. Both intrinsic and extrinsic variability were gradually revealed by reduction of tissue coupling. However, the recorded extrinsic variability between individual myocytes produced a greater degree of dispersion in repolarization in tissue than the intrinsic variability of each myocyte.


Assuntos
Fenômenos Eletrofisiológicos , Frequência Cardíaca/fisiologia , Coração/fisiologia , Modelos Cardiovasculares , Potenciais de Ação/fisiologia , Animais , Simulação por Computador , Cobaias , Processos Estocásticos , Fatores de Tempo
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