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AIMS: Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. METHODS AND RESULTS: In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. CONCLUSION: This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Animais , Cães , Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/terapia , Arritmias Cardíacas/terapia , Frequência Cardíaca , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.
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Inteligência Artificial , Cardiologia , Algoritmos , Humanos , Medicina de PrecisãoRESUMO
AIMS: There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response. METHODS AND RESULTS: In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01). CONCLUSION: Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.
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Bloqueio de Ramo/terapia , Terapia de Ressincronização Cardíaca , Frequência Cardíaca , Contração Miocárdica , Volume Sistólico , Função Ventricular Esquerda , Animais , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/fisiopatologia , Modelos Animais de Doenças , Cães , Feminino , Masculino , Recuperação de Função Fisiológica , Pressão VentricularRESUMO
AIMS: An abnormal large leftward septal motion prior to ejection is frequently observed in left bundle branch block (LBBB) patients. This motion has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate factors that influence its magnitude. METHODS AND RESULTS: Left (LVP) and right ventricular (RVP) pressures and left ventricular (LV) volume were measured in eight canines. After induction of LBBB, LVP and, hence, the transmural septal pressure (PLV-RV = LVP-RVP) increased more slowly (P < 0.01) during the phase when septum moved leftwards. A biventricular finite-element LBBB simulation model confirmed that the magnitude of septal leftward motion depended on reduced rise of PLV-RV. The model showed that leftward septal motion was decreased with shorter activation delay, reduced global or right ventricular (RV) contractility, septal infarction, or when the septum was already displaced into the LV at end diastole by RV volume overload. Both experiments and simulations showed that pre-ejection septal hypercontraction occurs, in part, because the septum performs more of the work pushing blood towards the mitral valve leaflets to close them as the normal lateral wall contribution to this push is lost. CONCLUSIONS: Left bundle branch block lowers afterload against pre-ejection septal contraction, expressed as slowed rise of PLV-RV, which is a main cause and determinant of the magnitude of leftward septal motion. The motion may be small or absent due to septal infarct, impaired global or RV contractility or RV volume overload, which should be kept in mind if this motion is to be used in evaluation of CRT response.
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Bloqueio de Ramo/fisiopatologia , Ventrículos do Coração/fisiopatologia , Valva Mitral/fisiopatologia , Modelos Cardiovasculares , Septo Interventricular/fisiopatologia , Animais , Terapia de Ressincronização Cardíaca , Modelos Animais de Doenças , Cães , Ecocardiografia , Eletrocardiografia , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Cardiac resynchronization therapy (CRT) has been proposed in heart failure patients with narrow QRS, but the mechanism of a potential beneficial effect is unknown. The present study investigated the hypothesis that left ventricular (LV) pacing increases LV end-diastolic volume (LVEDV) by allowing the LV to start filling before the right ventricle (RV) during narrow QRS in an experimental model. LV and biventricular pacing were studied in six anesthetized dogs before and after the induction of LV failure. Function was evaluated by pressures and dimensions, and dyssynchrony was evaluated by electromyograms and deformation. In the nonfailing heart, LV pacing gave the LV a head start in filling relative to the RV (P < 0.05) and increased LVEDV (P < 0.05). The response was similar during LV failure when RV diastolic pressure was elevated. The pacing-induced increase in LVEDV was attributed to a rightward shift of the septum (P < 0.01) due to an increased left-to-right transseptal pressure gradient (P < 0.05). LV pacing, however, also induced dyssynchrony (P < 0.05) and therefore reduced LV stroke work (P < 0.05) during baseline, and similar results were seen in failing hearts. Biventricular pacing did not change LVEDV, but systolic function was impaired. This effect was less marked than with LV pacing. In conclusion, pacing of the LV lateral wall increased LVEDV by displacing the septum rightward, suggesting a mechanism for a favorable effect of CRT in narrow QRS. The pacing, however, induced dyssynchrony and therefore reduced LV systolic function. These observations suggest that detrimental effects should be considered when applying CRT in patients with narrow QRS.
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Terapia de Ressincronização Cardíaca/métodos , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/terapia , Disfunção Ventricular Esquerda/terapia , Função Ventricular Esquerda , Animais , Modelos Animais de Doenças , Cães , Eletrocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Septos Cardíacos/fisiopatologia , Masculino , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Direita , Pressão VentricularRESUMO
OBJECTIVES: Cardiovascular failure is an important feature of severe sepsis and mortality in sepsis. The aim of our study was to explore myocardial dysfunction in severe sepsis. DESIGN: Prospective experimental study. SETTING: Operating room at Intervention Centre, Oslo University Hospital. SUBJECTS: Eight Norwegian Landrace pigs. INTERVENTIONS: The pigs were anesthetized, a medial sternotomy performed and miniature sensors for wall-thickness measurements attached to the epicardium and invasive pressure monitoring established, and an infusion of Escherichia coli started. Hemodynamic response was monitored and myocardial strain assessed by echocardiography. MEASUREMENTS AND MAIN RESULTS: Left ventricular myocardial function was significantly reduced assessed by longitudinal myocardial strain (-17.2% ± 2.8% to -12.3% ± 3.2%, p = 0.04), despite a reduced afterload as expressed by the left ventricular end-systolic meridional wall stress (35 ± 13 to 18 ± 8 kdyn/cm, p = 0.04). Left ventricular ejection fraction remained unaltered (48% ± 7% to 49% ± 5%, p = 0.4) as did cardiac output (6.3 ± 1.3 to 5.9 ± 3 L/min, p = 0.7). The decline in left ventricular function was further supported by significant reductions in the index of regional work by pressure-wall thickness loop area (121 ± 45 to 73 ± 37 mm × mm Hg, p = 0.005). Left ventricular myocardial wall thickness increased in both end diastole (11.5 ± 2.7 to 13.7 ± 2.4 mm, p = 0.03) and end systole (16.1 ± 2.9 to 18.5 ± 1.8 mm, p = 0.03), implying edema of the left ventricular myocardial wall. Right ventricular myocardial function by strain was reduced (-24.2% ± 4.1% to -16.9% ± 5.7%, p = 0.02). High right ventricular pressures caused septal shift as demonstrated by the end-diastolic transseptal pressure gradient (4.1 ± 3.3 to -2.2 ± 5.8 mm Hg, p = 0.01). CONCLUSIONS: The present study demonstrates myocardial dysfunction in severe sepsis. Strain echocardiography reveals myocardial dysfunction before significant changes in ejection fraction and cardiac output and could prove to be a useful tool in clinical evaluation of septic patients.
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Débito Cardíaco/fisiologia , Ecocardiografia Doppler/métodos , Ventrículos do Coração/diagnóstico por imagem , Miocárdio/patologia , Sepse/fisiopatologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Animais , Infecções por Escherichia coli , Hemodinâmica/fisiologia , Estudos Prospectivos , Sepse/diagnóstico por imagem , SuínosRESUMO
AIMS: The non-invasive myocardial work index (MWI) has been validated in patients without aortic stenosis (AS). A thorough assessment of methodological limitations is warranted before this index can be applied to patients with AS. METHODS AND RESULTS: We simultaneously measured left ventricular pressure (LVP) by using a micromanometer-tipped catheter and obtained echocardiograms in 20 patients with severe AS. We estimated LVP curves and calculated pressure-strain loops using three different models: (i) the model validated in patients without AS; (ii) the same model, but with pressure at the aortic valve opening (AVO) adjusted to diastolic cuff pressure; and (iii) a new model based on the invasive measurements from patients with AS. Valvular events were determined by echocardiography. Peak LVP was estimated as the sum of the mean aortic transvalvular gradient and systolic cuff pressure. In same-beat comparisons between invasive and estimated LVP curves, Model 1 significantly overestimated early systolic pressure by 61 ± 5 mmHg at AVO compared with Models 2 and 3. However, the average correlation coefficients between estimated and invasive LVP traces were excellent for all models, and the overestimation had limited influence on MWI, with excellent correlation (r = 0.98, P < 0.001) and good agreement between the MWI calculated with estimated (all models) and invasive LVP. CONCLUSION: This study confirms the validity of the non-invasive MWI in patients with AS. The accuracy of estimated LVP curves improved when matching AVO to the diastolic pressure in the original model, mirroring that of the AS-specific model. This may sequentially enhance the accuracy of regional MWI assessment.
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Estenose da Valva Aórtica , Humanos , Pressão Ventricular , Estenose da Valva Aórtica/diagnóstico por imagem , Miocárdio , Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Função Ventricular EsquerdaRESUMO
Cardiac valve event timing plays a crucial role when conducting clinical measurements using echocardiography. However, established automated approaches are limited by the need of external electrocardiogram sensors, and manual measurements often rely on timing from different cardiac cycles. Recent methods have applied deep learning to cardiac timing, but they have mainly been restricted to only detecting two key time points, namely end-diastole (ED) and end-systole (ES). In this work, we propose a deep learning approach that leverages triplane recordings to enhance detection of valve events in echocardiography. Our method demonstrates improved performance detecting six different events, including valve events conventionally associated with ED and ES. Of all events, we achieve an average absolute frame difference (aFD) of maximum 1.4 frames (29 ms) for start of diastasis, down to 0.6 frames (12 ms) for mitral valve opening when performing a ten-fold cross-validation with test splits on triplane data from 240 patients. On an external independent test consisting of apical long-axis data from 180 other patients, the worst performing event detection had an aFD of 1.8 (30 ms). The proposed approach has the potential to significantly impact clinical practice by enabling more accurate, rapid and comprehensive event detection, leading to improved clinical measurements.
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Aprendizado Profundo , Ecocardiografia , Humanos , Ecocardiografia/métodos , Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/fisiologia , Masculino , Interpretação de Imagem Assistida por Computador/métodosRESUMO
BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.
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BACKGROUND: Peak left ventricular (LV) untwisting rate (UTR) has been introduced as a clinical marker of diastolic function. This study investigates if early-diastolic load and restoring forces are determinants of UTR in addition to the rate of LV relaxation. METHODS AND RESULTS: In 10 anesthetized dogs we measured UTR by sonomicrometry and speckle tracking echocardiography at varying LV preloads, increased contractility, and myocardial ischemia. UTR was calculated as the time derivative of LV twist. Because preload modified end-diastolic twist, LV systolic twist was calculated in absolute terms with reference to the end-diastolic twist configuration at baseline. Relaxation rate was measured as the time constant (τ) of LV isovolumic pressure decay. Early-diastolic load was measured as LV pressure at the time of mitral valve opening. Circumferential-longitudinal shear strain was used as an index of restoring forces. In a multivariable mixed model analysis a strong association was observed between UTR and LV pressure at the time of mitral valve opening (parameter estimate [ß]=6.9; P<0.0001), indicating an independent effect of early-diastolic load. Furthermore, the associations between UTR and circumferential-longitudinal shear strain (ß=-11.3; P<0.0001) and τ (ß=-1.6, P<0.003) were consistent with independent contributions from restoring forces and rate of relaxation. Maximal UTR before mitral valve opening, however, was determined only by relaxation rate and restoring forces. CONCLUSIONS: The present study indicates that early-diastolic load, restoring forces, and relaxation rate are independent determinants of peak UTR. However, only relaxation rate and restoring forces contributed to UTR during isovolumic relaxation.
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Diástole/fisiologia , Modelos Cardiovasculares , Contração Miocárdica/fisiologia , Isquemia Miocárdica/fisiopatologia , Função Ventricular Esquerda/fisiologia , Doença Aguda , Animais , Cardiotônicos/farmacologia , Diástole/efeitos dos fármacos , Modelos Animais de Doenças , Dobutamina/farmacologia , Cães , Feminino , Hemodinâmica/fisiologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/diagnóstico por imagem , Resistência ao Cisalhamento/fisiologia , Estresse Mecânico , Torção Mecânica , Ultrassonografia , Veia Cava Superior/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/fisiologia , Suporte de Carga/fisiologiaRESUMO
AIMS: Left ventricular (LV) pressure-strain loop area reflects regional myocardial work and metabolic demand, but the clinical use of this index is limited by the need for invasive pressure. In this study, we introduce a non-invasive method to measure LV pressure-strain loop area. METHODS AND RESULTS: Left ventricular pressure was estimated by utilizing the profile of an empiric, normalized reference curve which was adjusted according to the duration of LV isovolumic and ejection phases, as defined by timing of aortic and mitral valve events by echocardiography. Absolute LV systolic pressure was set equal to arterial pressure measured invasively in dogs (n = 12) and non-invasively in patients (n = 18). In six patients, myocardial glucose metabolism was measured by positron emission tomography (PET). First, we studied anaesthetized dogs and observed an excellent correlation (r = 0.96) and a good agreement between estimated LV pressure-strain loop area and loop area by LV micromanometer and sonomicrometry. Secondly, we validated the method in patients with various cardiac disorders, including LV dyssynchrony, and confirmed an excellent correlation (r = 0.99) and a good agreement between pressure-strain loop areas using non-invasive and invasive LV pressure. Non-invasive pressure-strain loop area reflected work when incorporating changes in local LV geometry (r = 0.97) and showed a strong correlation with regional myocardial glucose metabolism by PET (r = 0.81). CONCLUSIONS: The novel non-invasive method for regional LV pressure-strain loop area corresponded well with invasive measurements and with directly measured myocardial work and it reflected myocardial metabolism. This method for assessment of regional work may be of clinical interest for several patients groups, including LV dyssynchrony and ischaemia.
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Miocárdio/metabolismo , Função Ventricular Esquerda/fisiologia , Pressão Ventricular/fisiologia , Idoso , Animais , Bloqueio de Ramo/fisiopatologia , Cães , Ecocardiografia , Feminino , Glucose/metabolismo , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Isquemia Miocárdica/fisiopatologia , Variações Dependentes do Observador , Tomografia por Emissão de Pósitrons , Valores de Referência , Estresse Fisiológico/fisiologia , Volume Sistólico/fisiologiaRESUMO
It has been debated whether intensive selection for growth and carcass yield in pig breeding programmes can affect the size of internal organs, and thereby reduce the animal's ability to handle stress and increase the risk of sudden deaths. To explore the respiratory and circulatory system in pigs, a deep learning based computational pipeline was built to extract the size of lungs and hearts from CT-scan images. This pipeline was applied on CT images from 11,000 boar selection candidates acquired during the last decade. Further, heart and lung volumes were analysed genetically and correlated with production traits. Both heart and lung volumes were heritable, with h2 estimated to 0.35 and 0.34, respectively, in Landrace, and 0.28 and 0.4 in Duroc. Both volumes were positively correlated with lean meat percentage, and lung volume was negatively genetically correlated with growth (rg = - 0.48 ± 0.07 for Landrace and rg = - 0.44 ± 0.07 for Duroc). The main findings suggest that the current pig breeding programs could, as an indirect response to selection, affect the size of hearts- and lungs. The presented methods can be used to monitor the development of internal organs in the future.
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Carne , Tomografia Computadorizada por Raios X , Animais , Masculino , Fenótipo , SuínosRESUMO
An abnormal systolic motion is frequently observed in patients with left bundle branch block (LBBB), and it has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate if this motion can be monitored with miniaturized sensors feasible for clinical use to identify response to CRT in real time. Motion sensors were attached to the septum and the left ventricular (LV) lateral wall of eighteen anesthetized dogs. Recordings were performed during baseline, after induction of LBBB, and during biventricular pacing. The abnormal contraction pattern in LBBB was quantified by the septal flash index (SFI) equal to the early systolic shortening of the LV septal-to-lateral wall diameter divided by the maximum shortening achieved during ejection. In baseline, with normal electrical activation, there was limited early-systolic shortening and SFI was low (9 ± 8%). After induction of LBBB, this shortening and the SFI significantly increased (88 ± 34%, p < 0.001). Subsequently, CRT reduced it approximately back to baseline values (13 ± 13%, p < 0.001 vs. LBBB). The study showed the feasibility of using miniaturized sensors for continuous monitoring of the abnormal systolic motion of the LV in LBBB and how such sensors can be used to assess response to pacing in real time to guide CRT implantation.
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BACKGROUND: Miniaturized accelerometers incorporated in pacing leads attached to the myocardium, are used to monitor cardiac function. For this purpose functional indices must be extracted from the acceleration signal. A method that automatically detects the time of aortic valve opening (AVO) and aortic valve closure (AVC) will be helpful for such extraction. We tested if deep learning can be used to detect these valve events from epicardially attached accelerometers, using high fidelity pressure measurements to establish ground truth for these valve events. METHOD: A deep neural network consisting of a CNN, an RNN, and a multi-head attention module was trained and tested on 130 recordings from 19 canines and 159 recordings from 27 porcines covering different interventions. Due to limited data, nested cross-validation was used to assess the accuracy of the method. RESULT: The correct detection rates were 98.9% and 97.1% for AVO and AVC in canines and 98.2% and 96.7% in porcines when defining a correct detection as a prediction closer than 40 ms to the ground truth. The incorrect detection rates were 0.7% and 2.3% for AVO and AVC in canines and 1.1% and 2.3% in porcines. The mean absolute error between correct detections and their ground truth was 8.4 ms and 7.2 ms for AVO and AVC in canines, and 8.9 ms and 10.1 ms in porcines. CONCLUSION: Deep neural networks can be used on signals from epicardially attached accelerometers for robust and accurate detection of the opening and closing of the aortic valve.
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Estenose da Valva Aórtica , Valva Aórtica , Acelerometria , Animais , Cães , Redes Neurais de ComputaçãoRESUMO
We investigated the determinants of ventricular early diastolic lengthening and mechanics of suction using a mathematical model of the left ventricle (LV). The model was based on a force balance between the force represented by LV pressure (LVP) and active and passive myocardial forces. The predicted lengthening velocity (e') from the model agreed well with measurements from 10 dogs during 5 different interventions (R = 0.69, P < 0.001). The model showed that e' was increased when relaxation rate and systolic shortening increased, when passive stiffness was decreased, and when the rate of fall of LVP during early filling was decreased relative to the rate of fall of active stress. We first defined suction as the work the myocardium performed to pull blood into the ventricle. This occurred when contractile active forces decayed below and became weaker than restoring forces, producing a negative LVP. An alternative definition of suction is filling during falling pressure, commonly believed to be caused by release of restoring forces. However, the model showed that this phenomenon also occurred when there had been no systolic compression below unstressed length and therefore in the absence of restoring forces. In conclusion, relaxation rate, LVP, systolic shortening, and passive stiffness were all independent determinants of e'. The model generated a suction effect seen as lengthening occurring during falling pressure. However, this was not equivalent with the myocardium performing pulling work on the blood, which was performed only when restoring forces were higher than remaining active fiber force, corresponding to a negative transmural pressure.
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Diástole/fisiologia , Modelos Teóricos , Função Ventricular Esquerda/fisiologia , Animais , Fenômenos Biomecânicos , Cães , Modelos Animais , Contração Miocárdica/fisiologiaRESUMO
During left bundle branch block (LBBB), electromechanical delay (EMD), defined as time from regional electrical activation (REA) to onset shortening, is prolonged in the late-activated left ventricular lateral wall compared with the septum. This leads to greater mechanical relative to electrical dyssynchrony. The aim of this study was to determine the mechanism of the prolonged EMD. We investigated this phenomenon in an experimental LBBB dog model (n = 7), in patients (n = 9) with biventricular pacing devices, in an in vitro papillary muscle study (n = 6), and a mathematical simulation model. Pressures, myocardial deformation, and REA were assessed. In the dogs, there was a greater mechanical than electrical delay (82 ± 12 vs. 54 ± 8 ms, P = 0.002) due to prolonged EMD in the lateral wall vs. septum (39 ± 8 vs.11 ± 9 ms, P = 0.002). The prolonged EMD in later activated myocardium could not be explained by increased excitation-contraction coupling time or increased pressure at the time of REA but was strongly related to dP/dt at the time of REA (r = 0.88). Results in humans were consistent with experimental findings. The papillary muscle study and mathematical model showed that EMD was prolonged at higher dP/dt because it took longer for the segment to generate active force at a rate superior to the load rise, which is a requirement for shortening. We conclude that, during LBBB, prolonged EMD in late-activated myocardium is caused by a higher dP/dt at the time of activation, resulting in aggravated mechanical relative to electrical dyssynchrony. These findings suggest that LV contractility may modify mechanical dyssynchrony.
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Bloqueio de Ramo/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Músculos Papilares/fisiopatologia , Idoso , Animais , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/terapia , Terapia de Ressincronização Cardíaca , Simulação por Computador , Modelos Animais de Doenças , Cães , Eletrocardiografia , Eletromiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Contração Miocárdica , Proibitinas , Coelhos , Fatores de Tempo , Função Ventricular Esquerda , Pressão VentricularRESUMO
AIMS: We tested the hypothesis that shortening of time-to-peak left ventricular pressure rise (Td) reflect resynchronization in an animal model and that Td measured in patients will be helpful to identify long-term volumetric responders [end-systolic volume (ESV) decrease >15%] in cardiac resynchronization therapy (CRT). METHODS: Td was analysed in an animal study (n = 12) of left bundle-branch block (LBBB) with extensive instrumentation to detect left ventricular myocardial deformation, electrical activation, and pressures during pacing. The sum of electrical delays from the onset of pacing to four intracardiac electrodes formed a synchronicity index (SI). Pacing was performed at baseline, with LBBB, right and left ventricular pacing and finally with biventricular pacing (BIVP). We then studied Td at baseline and with BIVP in a clinical observational study in 45 patients during the implantation of CRT and followed up for up to 88 months. RESULTS: We found a strong relationship between Td and SI in the animals (R = 0.84, P < 0.01). Td and SI increased from narrow QRS at baseline (Td = 95 ± 2 ms, SI = 141 ± 8 ms) to LBBB (Td = 125 ± 2 ms, SI = 247 ± 9 ms, P < 0.01), and shortened with biventricular pacing (BIVP) (Td = 113 ± 2 ms and SI = 192 ± 7 ms, P < 0.01). Prolongation of Td was associated with more wasted deformation during the preejection period (R = 0.77, P < 0.01). Six patients increased ESV by 2.5 ± 18%, while 37 responders (85%) had a mean ESV decrease of 40 ± 15% after more than 6 months of follow-up. Responders presented with a higher Td at baseline than non-responders (163 ± 26 ms vs. 121 ± 19 ms, P < 0.01). Td decreased to 156 ± 16 ms (P = 0.02) with CRT in responders, while in non-responders, Td increased to 148 ± 21 ms (P < 0.01). A decrease in Td with BIVP to values similar or below what was found at baseline accurately identified responders to therapy (AUC 0.98, P < 0.01). Td at baseline and change in Td from baseline was linear related to the decrease in ESV at follow-up. All-cause mortality was high among six non-responders (n = 4), while no patients died in the responder group during follow-up. CONCLUSIONS: Prolongation of Td is associated with cardiac dyssynchrony and more wasted deformation during the preejection period. Shortening of a prolonged Td with CRT in patients accurately identifies volumetric responders to CRT with incremental value on top of current guidelines and practices. Thus, Td carries the potential to become a biomarker to predict long-term volumetric response in CRT candidates.
Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Animais , Arritmias Cardíacas/complicações , Bloqueio de Ramo/terapia , Humanos , Pressão VentricularRESUMO
This study describes results from an experimental ultrasound system with miniature transducers sutured directly onto the epicardial surface and used to measure heart contractions continuously. This system was used to find velocity distributions through the myocardium. The resulting velocities were used to track the motion of four layers at different depths through the myocardium and to find the regional strain in each of the four layers. Velocities inside the myocardium vary from the epicardial to the endocardial borders. Conventional velocity estimators based on Doppler and on time delay estimation were modified to better handle these variations. Results from four different velocity estimators were tested against a simulation model for ultrasound echoes from moving tissue and on ultrasound recordings from five animals. We observed that the tested velocity estimators were able to reproduce the myocardial velocity distributions, track the myocardial layer motion and estimate strain at different positions inside the myocardium for both simulated and real ultrasound recordings. The most accurate results were obtained when the digitized ultrasound scanlines were upsampled by a factor of 10 before applying cross-correlation to estimate time delays. A modified Doppler algorithm allowing the velocity to vary linearly with time throughout the duration of the pulse packet (constant acceleration Doppler) was found to be better at capturing rapidly changing velocities compared with conventional Doppler processing. The best results were obtained using upsamling and time delay estimation, but the long computation time required by this method may make it best suited in a laboratory setting. In a real-time system, the computationally quicker constant acceleration Doppler may be preferred.
Assuntos
Contração Miocárdica/fisiologia , Pericárdio/fisiologia , Ultrassonografia Doppler , Animais , Miniaturização , Modelos Teóricos , Suínos , TransdutoresRESUMO
OBJECTIVE: A miniaturized accelerometer can be incorporated in temporary pacemaker leads which are routinely attached to the epicardium during cardiac surgery and provide continuous monitoring of cardiac motion during and following surgery. We tested if such a sensor could be used to assess volume status, which is essential in hemodynamically unstable patients. METHODS: An accelerometer was attached to the epicardium of 9 pigs and recordings performed during baseline, fluid loading, and phlebotomy in a closed chest condition. Alterations in left ventricular (LV) preload alter myocardial tension which affects the frequency of myocardial acceleration associated with the first heart sound ( fS1). The accuracy of fS1 as an estimate of preload was evaluated using sonomicrometry measured end-diastolic volume (EDV[Formula: see text]). Standard clinical estimates of global end-diastolic volume using pulse index continuous cardiac output (PiCCO) measurements (GEDV[Formula: see text]) and pulmonary artery occlusion pressure (PAOP) were obtained for comparison. The diagnostic accuracy of identifying fluid responsiveness was analyzed for fS1, stroke volume variation (SVV[Formula: see text]), pulse pressure variation (PPV[Formula: see text]), GEDV[Formula: see text], and PAOP. RESULTS: Changes in fS1 correlated well to changes in EDV[Formula: see text] ( r2=0.81, 95%CI: [0.68, 0.89]), as did GEDV[Formula: see text] ( r2=0.59, 95%CI: [0.36, 0.76]) and PAOP ( r2=0.36, 95%CI: [0.01, 0.73]). The diagnostic accuracy [95%CI] in identifying fluid responsiveness was 0.79 [0.66, 0.94] for fS1, 0.72 [0.57, 0.86] for SVV[Formula: see text], and 0.63 (0.44, 0.82) for PAOP. CONCLUSION: An epicardially placed accelerometer can assess changes in preload in real-time. SIGNIFICANCE: This novel method can facilitate continuous monitoring of the volemic status in open-heart surgery patients and help guiding fluid resuscitation.