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Background: Diastolic left ventricular (LV) dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed LV systolic function, the E/A ratio, the ratio between the peak early (E) and the peak late (A) transmitral flow velocity, is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography (echo) is the preferred imaging technique for diastolic function assessment, while cardiovascular magnetic resonance (CMR) is less established as a method. Previous four-dimensional (4D) Flow -based studies have looked at the E/A ratio proximal to the mitral valve, requiring manual interaction. In this study, we compare an automated, deep learning -based and two semi -automated approaches for 4D Flow CMR-based E/A ratio assessment to conventional, gold -standard echo -based methods. Methods: Ninety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by CMR investigation. 4D Flow -based E/A ratio values were computed using three different approaches; two semi -automated, assessing the E/A ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning -based method with which the E/A ratio could be assessed without constraint to the mitral plane (LVvel). Results: MVvel, MVflow, and LVvel E/A ratios were strongly associated with echocardiographically derived E/A ratio (R 2 = 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R 2 = 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed a strong association (R 2 = 0.26, 0.57). Conclusion: Peak E, peak A, and E/A ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in, Funding Agencies|Swedish Research Council [2022-03931]; Swedish Heart and Lung Foundation [20210441]; ALF Grants Region stergtland [R-987498]; Sweden's Innovation Agency Vinnova [2019-02261]; EU [223615]

Plain language summaryAssessing the blood flow inside the heart is important in diagnosis and treatment of various cardiovascular diseases, such as atrial fibrillation or heart failure. We developed a method to accurately track the motion of the heart walls over the course of a heartbeat in three-dimensional Computed Tomography (CT) images. Based on the motion, we calculated the amount of blood passing through the mitral valve and the left atrial appendage orifice, which are markers used in the diagnostic of heart failure and assessment of stroke risk in atrial fibrillation. The results agreed well with measurements from 4D flow MRI, an imaging technique that measures blood velocities. Our method could broaden the use of CT and make additional exams redundant. It can even be used to calculate the blood flow inside the heart. BackgroundCardiac time-resolved CT (4D-CT) acquisitions provide high quality anatomical images of the heart. However, some cardiac diseases require assessment of blood flow in the heart. Diastolic dysfunction, for instance, is diagnosed by measuring the flow through the mitral valve (MV), while in atrial fibrillation, the flow through the left atrial appendage (LAA) indicates the risk for thrombus formation. Accurate validated techniques to extract this information from 4D-CT have been lacking, however.MethodsTo measure the flow rate though the MV and the LAA from 4D-CT, we developed a motion tracking algorithm that performs a nonrigid deformation of the surface separating the blood pool from the myocardium. To improve the tracking of the LAA, this region was deformed separately from the left atrium and left ventricle. We compared the CT based flow with 4D flow and short axis MRI data from the same individual in 9 patients.ResultsFor the mitral valve flow, good agreement was found for the time span between the early and late diastolic peak flow (bias: <0.1 s). The ventricular stroke volume is similar compared to short-axis MRI (bias 3 ml)

Plain language summaryAssessing the blood flow inside the heart is important in diagnosis and treatment of various cardiovascular diseases, such as atrial fibrillation or heart failure. We developed a method to accurately track the motion of the heart walls over the course of a heartbeat in three-dimensional Computed Tomography (CT) images. Based on the motion, we calculated the amount of blood passing through the mitral valve and the left atrial appendage orifice, which are markers used in the diagnostic of heart failure and assessment of stroke risk in atrial fibrillation. The results agreed well with measurements from 4D flow MRI, an imaging technique that measures blood velocities. Our method could broaden the use of CT and make additional exams redundant. It can even be used to calculate the blood flow inside the heart. BackgroundCardiac time-resolved CT (4D-CT) acquisitions provide high quality anatomical images of the heart. However, some cardiac diseases require assessment of blood flow in the heart. Diastolic dysfunction, for instance, is diagnosed by measuring the flow through the mitral valve (MV), while in atrial fibrillation, the flow through the left atrial appendage (LAA) indicates the risk for thrombus formation. Accurate validated techniques to extract this information from 4D-CT have been lacking, however.MethodsTo measure the flow rate though the MV and the LAA from 4D-CT, we developed a motion tracking algorithm that performs a nonrigid deformation of the surface separating the blood pool from the myocardium. To improve the tracking of the LAA, this region was deformed separately from the left atrium and left ventricle. We compared the CT based flow with 4D flow and short axis MRI data from the same individual in 9 patients.ResultsFor the mitral valve flow, good agreement was found for the time span between the early and late diastolic peak flow (bias: <0.1 s). The ventricular stroke volume is similar compared to short-axis MRI (bias 3 ml)

Plain language summaryAssessing the blood flow inside the heart is important in diagnosis and treatment of various cardiovascular diseases, such as atrial fibrillation or heart failure. We developed a method to accurately track the motion of the heart walls over the course of a heartbeat in three-dimensional Computed Tomography (CT) images. Based on the motion, we calculated the amount of blood passing through the mitral valve and the left atrial appendage orifice, which are markers used in the diagnostic of heart failure and assessment of stroke risk in atrial fibrillation. The results agreed well with measurements from 4D flow MRI, an imaging technique that measures blood velocities. Our method could broaden the use of CT and make additional exams redundant. It can even be used to calculate the blood flow inside the heart. BackgroundCardiac time-resolved CT (4D-CT) acquisitions provide high quality anatomical images of the heart. However, some cardiac diseases require assessment of blood flow in the heart. Diastolic dysfunction, for instance, is diagnosed by measuring the flow through the mitral valve (MV), while in atrial fibrillation, the flow through the left atrial appendage (LAA) indicates the risk for thrombus formation. Accurate validated techniques to extract this information from 4D-CT have been lacking, however.MethodsTo measure the flow rate though the MV and the LAA from 4D-CT, we developed a motion tracking algorithm that performs a nonrigid deformation of the surface separating the blood pool from the myocardium. To improve the tracking of the LAA, this region was deformed separately from the left atrium and left ventricle. We compared the CT based flow with 4D flow and short axis MRI data from the same individual in 9 patients.ResultsFor the mitral valve flow, good agreement was found for the time span between the early and late diastolic peak flow (bias: <0.1 s). The ventricular stroke volume is similar compared to short-axis MRI (bias 3 ml)

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 4D Flow CMR Consensus Statement. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

Plain language summaryAssessing the blood flow inside the heart is important in diagnosis and treatment of various cardiovascular diseases, such as atrial fibrillation or heart failure. We developed a method to accurately track the motion of the heart walls over the course of a heartbeat in three-dimensional Computed Tomography (CT) images. Based on the motion, we calculated the amount of blood passing through the mitral valve and the left atrial appendage orifice, which are markers used in the diagnostic of heart failure and assessment of stroke risk in atrial fibrillation. The results agreed well with measurements from 4D flow MRI, an imaging technique that measures blood velocities. Our method could broaden the use of CT and make additional exams redundant. It can even be used to calculate the blood flow inside the heart. BackgroundCardiac time-resolved CT (4D-CT) acquisitions provide high quality anatomical images of the heart. However, some cardiac diseases require assessment of blood flow in the heart. Diastolic dysfunction, for instance, is diagnosed by measuring the flow through the mitral valve (MV), while in atrial fibrillation, the flow through the left atrial appendage (LAA) indicates the risk for thrombus formation. Accurate validated techniques to extract this information from 4D-CT have been lacking, however.MethodsTo measure the flow rate though the MV and the LAA from 4D-CT, we developed a motion tracking algorithm that performs a nonrigid deformation of the surface separating the blood pool from the myocardium. To improve the tracking of the LAA, this region was deformed separately from the left atrium and left ventricle. We compared the CT based flow with 4D flow and short axis MRI data from the same individual in 9 patients.ResultsFor the mitral valve flow, good agreement was found for the time span between the early and late diastolic peak flow (bias: <0.1 s). The ventricular stroke volume is similar compared to short-axis MRI (bias 3 ml)

Plain language summaryAssessing the blood flow inside the heart is important in diagnosis and treatment of various cardiovascular diseases, such as atrial fibrillation or heart failure. We developed a method to accurately track the motion of the heart walls over the course of a heartbeat in three-dimensional Computed Tomography (CT) images. Based on the motion, we calculated the amount of blood passing through the mitral valve and the left atrial appendage orifice, which are markers used in the diagnostic of heart failure and assessment of stroke risk in atrial fibrillation. The results agreed well with measurements from 4D flow MRI, an imaging technique that measures blood velocities. Our method could broaden the use of CT and make additional exams redundant. It can even be used to calculate the blood flow inside the heart. BackgroundCardiac time-resolved CT (4D-CT) acquisitions provide high quality anatomical images of the heart. However, some cardiac diseases require assessment of blood flow in the heart. Diastolic dysfunction, for instance, is diagnosed by measuring the flow through the mitral valve (MV), while in atrial fibrillation, the flow through the left atrial appendage (LAA) indicates the risk for thrombus formation. Accurate validated techniques to extract this information from 4D-CT have been lacking, however.MethodsTo measure the flow rate though the MV and the LAA from 4D-CT, we developed a motion tracking algorithm that performs a nonrigid deformation of the surface separating the blood pool from the myocardium. To improve the tracking of the LAA, this region was deformed separately from the left atrium and left ventricle. We compared the CT based flow with 4D flow and short axis MRI data from the same individual in 9 patients.ResultsFor the mitral valve flow, good agreement was found for the time span between the early and late diastolic peak flow (bias: <0.1 s). The ventricular stroke volume is similar compared to short-axis MRI (bias 3 ml)

Funding agencies: This study was partially financed through ALF Grants, Region Ostergotland LIO-284291, LIO-284411, and LIO-448281, and LIU Cancer Projects Grants 2012.

Funding agencies: This study was partially financed through ALF Grants, Region Ostergotland LIO-284291, LIO-284411, and LIO-448281, and LIU Cancer Projects Grants 2012.

Funding agencies: This study was partially financed through ALF Grants, Region Ostergotland LIO-284291, LIO-284411, and LIO-448281, and LIU Cancer Projects Grants 2012.

Funding agencies: This study was partially financed through ALF Grants, Region Ostergotland LIO-284291, LIO-284411, and LIO-448281, and LIU Cancer Projects Grants 2012.

Funding agencies: This study was partially financed through ALF Grants, Region Ostergotland LIO-284291, LIO-284411, and LIO-448281, and LIU Cancer Projects Grants 2012.

Significant mitral valve regurgitation creates progressive adverse remodeling of the left ventricle (LV). Replacement of the failing valve with a prosthesis generally improves patient outcomes but leaves the patient with non-physiological intracardiac flow patterns that might contribute to their future risk of thrombus formation and embolism. It has been suggested that the angular orientation of the implanted valve might modify the postoperative distortion of the intraventricular flow field. In this study, we investigated the effect of prosthetic valve orientation on LV flow patterns by using heart geometry from a patient with LV dysfunction and a competent native mitral valve to calculate intracardiac flow fields with computational fluid dynamics (CFD). Results were validated using in vivo 4D Flow MRI. The computed flow fields were compared to calculations following virtual implantation of a mechanical heart valve oriented in four different angles to assess the effect of leaflet position. Flow patterns were visualized in longand short-axes and quantified with flow component analysis. In comparison to a native valve, valve implantation increased the proportion of the mitral inflow remaining in the basal region and further increased the residual volume in the apical area. Only slight changes due to valve orientation were observed. Using our numerical framework, we demonstrated quantitative changes in left ventricular blood flow due to prosthetic mitral replacement. This framework may be used to improve design of prosthetic heart valves and implantation procedures to minimize the potential for apical flow stasis, and potentially assist personalized treatment planning. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Funding Agencies|Knut and Alice Wallenberg Foundation through the project Seeing Organ Function; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation; VinnovaVinnova; Swedish Research CouncilSwedish Research CouncilEuropean Commission; County Council of Ostergotland

Significant mitral valve regurgitation creates progressive adverse remodeling of the left ventricle (LV). Replacement of the failing valve with a prosthesis generally improves patient outcomes but leaves the patient with non-physiological intracardiac flow patterns that might contribute to their future risk of thrombus formation and embolism. It has been suggested that the angular orientation of the implanted valve might modify the postoperative distortion of the intraventricular flow field. In this study, we investigated the effect of prosthetic valve orientation on LV flow patterns by using heart geometry from a patient with LV dysfunction and a competent native mitral valve to calculate intracardiac flow fields with computational fluid dynamics (CFD). Results were validated using in vivo 4D Flow MRI. The computed flow fields were compared to calculations following virtual implantation of a mechanical heart valve oriented in four different angles to assess the effect of leaflet position. Flow patterns were visualized in longand short-axes and quantified with flow component analysis. In comparison to a native valve, valve implantation increased the proportion of the mitral inflow remaining in the basal region and further increased the residual volume in the apical area. Only slight changes due to valve orientation were observed. Using our numerical framework, we demonstrated quantitative changes in left ventricular blood flow due to prosthetic mitral replacement. This framework may be used to improve design of prosthetic heart valves and implantation procedures to minimize the potential for apical flow stasis, and potentially assist personalized treatment planning. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Funding Agencies|Knut and Alice Wallenberg Foundation through the project Seeing Organ Function; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation; VinnovaVinnova; Swedish Research CouncilSwedish Research CouncilEuropean Commission; County Council of Ostergotland

Significant mitral valve regurgitation creates progressive adverse remodeling of the left ventricle (LV). Replacement of the failing valve with a prosthesis generally improves patient outcomes but leaves the patient with non-physiological intracardiac flow patterns that might contribute to their future risk of thrombus formation and embolism. It has been suggested that the angular orientation of the implanted valve might modify the postoperative distortion of the intraventricular flow field. In this study, we investigated the effect of prosthetic valve orientation on LV flow patterns by using heart geometry from a patient with LV dysfunction and a competent native mitral valve to calculate intracardiac flow fields with computational fluid dynamics (CFD). Results were validated using in vivo 4D Flow MRI. The computed flow fields were compared to calculations following virtual implantation of a mechanical heart valve oriented in four different angles to assess the effect of leaflet position. Flow patterns were visualized in longand short-axes and quantified with flow component analysis. In comparison to a native valve, valve implantation increased the proportion of the mitral inflow remaining in the basal region and further increased the residual volume in the apical area. Only slight changes due to valve orientation were observed. Using our numerical framework, we demonstrated quantitative changes in left ventricular blood flow due to prosthetic mitral replacement. This framework may be used to improve design of prosthetic heart valves and implantation procedures to minimize the potential for apical flow stasis, and potentially assist personalized treatment planning. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Funding Agencies|Knut and Alice Wallenberg Foundation through the project Seeing Organ Function; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation; VinnovaVinnova; Swedish Research CouncilSwedish Research CouncilEuropean Commission; County Council of Ostergotland

Significant mitral valve regurgitation creates progressive adverse remodeling of the left ventricle (LV). Replacement of the failing valve with a prosthesis generally improves patient outcomes but leaves the patient with non-physiological intracardiac flow patterns that might contribute to their future risk of thrombus formation and embolism. It has been suggested that the angular orientation of the implanted valve might modify the postoperative distortion of the intraventricular flow field. In this study, we investigated the effect of prosthetic valve orientation on LV flow patterns by using heart geometry from a patient with LV dysfunction and a competent native mitral valve to calculate intracardiac flow fields with computational fluid dynamics (CFD). Results were validated using in vivo 4D Flow MRI. The computed flow fields were compared to calculations following virtual implantation of a mechanical heart valve oriented in four different angles to assess the effect of leaflet position. Flow patterns were visualized in longand short-axes and quantified with flow component analysis. In comparison to a native valve, valve implantation increased the proportion of the mitral inflow remaining in the basal region and further increased the residual volume in the apical area. Only slight changes due to valve orientation were observed. Using our numerical framework, we demonstrated quantitative changes in left ventricular blood flow due to prosthetic mitral replacement. This framework may be used to improve design of prosthetic heart valves and implantation procedures to minimize the potential for apical flow stasis, and potentially assist personalized treatment planning. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Funding Agencies|Knut and Alice Wallenberg Foundation through the project Seeing Organ Function; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation; VinnovaVinnova; Swedish Research CouncilSwedish Research CouncilEuropean Commission; County Council of Ostergotland

Significant mitral valve regurgitation creates progressive adverse remodeling of the left ventricle (LV). Replacement of the failing valve with a prosthesis generally improves patient outcomes but leaves the patient with non-physiological intracardiac flow patterns that might contribute to their future risk of thrombus formation and embolism. It has been suggested that the angular orientation of the implanted valve might modify the postoperative distortion of the intraventricular flow field. In this study, we investigated the effect of prosthetic valve orientation on LV flow patterns by using heart geometry from a patient with LV dysfunction and a competent native mitral valve to calculate intracardiac flow fields with computational fluid dynamics (CFD). Results were validated using in vivo 4D Flow MRI. The computed flow fields were compared to calculations following virtual implantation of a mechanical heart valve oriented in four different angles to assess the effect of leaflet position. Flow patterns were visualized in longand short-axes and quantified with flow component analysis. In comparison to a native valve, valve implantation increased the proportion of the mitral inflow remaining in the basal region and further increased the residual volume in the apical area. Only slight changes due to valve orientation were observed. Using our numerical framework, we demonstrated quantitative changes in left ventricular blood flow due to prosthetic mitral replacement. This framework may be used to improve design of prosthetic heart valves and implantation procedures to minimize the potential for apical flow stasis, and potentially assist personalized treatment planning. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., Funding Agencies|Knut and Alice Wallenberg Foundation through the project Seeing Organ Function; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation; VinnovaVinnova; Swedish Research CouncilSwedish Research CouncilEuropean Commission; County Council of Ostergotland

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion. Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate similar to 60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated. Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase. Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusi, Funding Agencies|Swedish Medical Research CouncilSwedish Medical Research Council (SMRC) [2018-02779]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20170440]; ALF Grants Region Ostergotland [LIO-797721]

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion. Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate similar to 60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated. Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase. Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusi, Funding Agencies|Swedish Medical Research CouncilSwedish Medical Research Council (SMRC) [2018-02779]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20170440]; ALF Grants Region Ostergotland [LIO-797721]

Correction to: Scientifc Reports https://doi.org/10.1038/s41598-017-06339-0

Correction to: Scientifc Reports https://doi.org/10.1038/s41598-017-06339-0

Correction to: Scientifc Reports https://doi.org/10.1038/s41598-017-06339-0

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion. Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate similar to 60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated. Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase. Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusi, Funding Agencies|Swedish Medical Research CouncilSwedish Medical Research Council (SMRC) [2018-02779]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20170440]; ALF Grants Region Ostergotland [LIO-797721]

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion. Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate similar to 60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated. Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase. Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusi, Funding Agencies|Swedish Medical Research CouncilSwedish Medical Research Council (SMRC) [2018-02779]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20170440]; ALF Grants Region Ostergotland [LIO-797721]

Correction to: Scientifc Reports https://doi.org/10.1038/s41598-017-06339-0

Correction to: Scientifc Reports https://doi.org/10.1038/s41598-017-06339-0

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion. Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate similar to 60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated. Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase. Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusi, Funding Agencies|Swedish Medical Research CouncilSwedish Medical Research Council (SMRC) [2018-02779]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20170440]; ALF Grants Region Ostergotland [LIO-797721]

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics, Funding Agencies|European Union [310612]; Swedish Research Council [621-2014-6191]; Swedish Heart and Lung Foundation [20140398]

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics, Funding Agencies|European Union [310612]; Swedish Research Council [621-2014-6191]; Swedish Heart and Lung Foundation [20140398]

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood's timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P = 0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy., Funding agencies: Swedish Heart and Lung Foundation [20140398]; Swedish Research Council [621-2014-6191]; European Research Council [310612]

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood's timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P = 0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy., Funding agencies: Swedish Heart and Lung Foundation [20140398]; Swedish Research Council [621-2014-6191]; European Research Council [310612]

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics, Funding Agencies|European Union [310612]; Swedish Research Council [621-2014-6191]; Swedish Heart and Lung Foundation [20140398]

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood's timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P = 0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy., Funding agencies: Swedish Heart and Lung Foundation [20140398]; Swedish Research Council [621-2014-6191]; European Research Council [310612]

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics, Funding Agencies|European Union [310612]; Swedish Research Council [621-2014-6191]; Swedish Heart and Lung Foundation [20140398]

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood's timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P = 0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy., Funding agencies: Swedish Heart and Lung Foundation [20140398]; Swedish Research Council [621-2014-6191]; European Research Council [310612]

Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics, Funding Agencies|European Union [310612]; Swedish Research Council [621-2014-6191]; Swedish Heart and Lung Foundation [20140398]

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood's timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P = 0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy., Funding agencies: Swedish Heart and Lung Foundation [20140398]; Swedish Research Council [621-2014-6191]; European Research Council [310612]

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Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements., Funding Agencies|European Research Council [310612]; Swedish Research Council [2014-6191]

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT., Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Research Council [310612]

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT., Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Research Council [310612]

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT., Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Research Council [310612]

Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements., Funding Agencies|European Research Council [310612]; Swedish Research Council [2014-6191]

Lumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements., Funding Agencies|European Research Council [310612]; Swedish Research Council [2014-6191]

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT., Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Research Council [310612]