Ignite Creation Date:
2024-05-06 @ 7:44 PM
Last Modification Date:
2024-10-26 @ 3:12 PM
Study NCT ID:
NCT06115096
Status:
RECRUITING
Last Update Posted:
2023-11-02
First Post:
2023-10-16
Brief Title:
Cardiac Hemodynamics During Left Ventricular Assist
Sponsor:
Region Östergötland
Organization:
Region Östergötland
Study Overview
Official Title:
Exploration of Intracardiac Geometry and Hemodynamics During HeartMate 3 Therapy A Novel Approach Using Photon-Counting CT and Computational Fluid Dynamics
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FlowVAD
Brief Summary:
The goal of this observational study is to exploratively investigate intracardiac geometry and hemodynamics in patients with ongoing HeartMate 3-therapy in the Swedish Southeast Healthcare region The main question it aims to answer is
- How do different flow levels in the HeartMate 3 left ventricular assist system influence intracardiac geometry and hemodynamics
Participating research subjects are called upon to undergo three followed photon-counting CT scans as well as certain echocardiographic imaging all in one session The research subjects HeartMate device is connected to software that allows for variations in the pumps flow between these image collections Analyzed variables includes three-dimensional geometry CFD-computed parameters such as blood velocity pressure turbulence and blood stasis The variables are related with device settings and alongside selected echocardiographic measurements and patient details such as age BMI and diagnostic codes for both method validation and comprehensive perspective
- How do different flow levels in the HeartMate 3 left ventricular assist system influence intracardiac geometry and hemodynamics
Participating research subjects are called upon to undergo three followed photon-counting CT scans as well as certain echocardiographic imaging all in one session The research subjects HeartMate device is connected to software that allows for variations in the pumps flow between these image collections Analyzed variables includes three-dimensional geometry CFD-computed parameters such as blood velocity pressure turbulence and blood stasis The variables are related with device settings and alongside selected echocardiographic measurements and patient details such as age BMI and diagnostic codes for both method validation and comprehensive perspective
Detailed Description:
1 BACKGROUND
In recent years the use of the mechanical circulatory support device HeartMate 3 HM3 Abbott Laboratories Lake Forest IL has garnered significant attention in the realm of circulatory support for advanced heart failure The tangible advantages of the HM3 including enhanced hemocompatibility leading to reduced thromboembolic events and improved survival rates compared to its predecessors The transition towards HM3 is particularly noteworthy as the system is not only likely to serve as a bridge to heart transplantation or decision-making but is increasingly being discussed as an effective destination therapy Despite these advancements there remains an imperative for meticulous hemodynamic monitoring throughout any mechanical circulatory support treatment Traditionally echocardiography has been predominantly employed as the hemodynamic imaging modality However echocardiographic evaluations of these patients present notable challenges especially concerning shadows from the pumps metal making it difficult to fully comprehend cardiac function and hemodynamics during the treatment
Over the past decade computed tomography CT has seen rapid advancements with modern equipment now facilitating high-resolution anatomical imaging of the heart throughout the cardiac cycle 4D CT Until recently however CT also posed a challenge for the examination of patients with mechanical circulatory support devices due to significant metal artifacts The newly introduced photon-counting computed tomography PC-CT however now enables scans that yield higher resolution images with reduced metal artifacts From time-resolved CT functional information can subsequently be derived and extracted Techniques for automatic tracking of cardiac wall motion throughout the cardiac cycle along with the utilization of computational dynamics to numerically solve fluid mechanical equations have previously been shown which have proven to enable simulations of intracardiac hemodynamic maps
The increasing indications for treatment with mechanical circulatory support underscore the current demand for continuously improved care quality and clinical understanding of this therapeutic option Although the treatment enhances both prognosis and quality of life serious and fatal complications remain recurrent To the knowledge of the investigators there has yet been no conducted research addressing the potential application of the novel PC-CT in patients with mechanical circulatory support devices and certainly none that have established numerical frameworks on this data in an attempt to compute visualize and exploratively understand intracardiac hemodynamics during the treatment
12 OBJECTIVES
121 AIM
The aim of this observational study is to exploratively investigate intracardiac geometry and hemodynamics in patients with ongoing HeartMate 3-therapy in the Swedish Southeast Healthcare region
122 PRIMARY SCIENTIFIC QUESTION
How do different flow levels in the HeartMate 3 left ventricular assist device influence intracardiac geometry and hemodynamics
2 METHODS
21 STUDY DESIGN
This study has an explorative analytic multiple cross-sectional design The study seeks to uncover new insights patterns and associations within the data partly without predetermined hypotheses Further the study investigates relationships or associations between variables to derive meaningful conclusions from the data The study will examine three distinct observations of the variables wherein the subjects device settings will vary These observations however will be executed in close temporal proximity with intervals of approximately 15 minutes between each As such while the study does not fully conform to the criteria of a multiple cross-sectional study design it also does not align with a traditional one-time-point cross-sectional approach
22 OVERALL SETTING
Participating research subjects are called upon to undergo three followed PC-CT scans as well as certain echocardiographic imaging all in one session The research subjects HM3 is connected to software that allows for variations in the pumps flow between these image collections All examinations will be performed at Center for Medical Image Science and Visualization CMIV at Linköping University Sweden Recruitment and examination within the study will undergo during January-December 2023 The study has been approved by the Swedish ethics review authority Reference number 2022-06934-01
22 PARTICIPANTS
All patients within the Swedish Southeastern healthcare region encompassing Östergötland Jönköping and Kalmar counties who meet the inclusion criteria and none of the exclusion criteria will be invited to participate in this study during 2023 Screening for inclusion is conducted by the LVAD-responsible physicians within the Cardiology Department at Linköping University Hospital
23 VARIABLES
Regarding specification of variables that will be studied it is essential to clarify that due to the exploratory nature of the research and the intricate dynamics inherent to both using numerical frameworks for calculating intracardiac hemodynamic maps and the dynamic geometric nature of time-resolved CT all variables at the study onset are not pre-defined As the analysis progresses and the full depth of the data becomes apparent additional variables may be identified and incorporated Subsequent decision-making process relating to the inclusion or exclusion of these newly discovered variables will be rigorously documented to ensure transparency and robustness in the study approach
Quantified variables will be compared with respect to the pumps estimated flow Lmin power W pulsatility index and rotor speed rpm Whenever possible based on image quality the results will also be related to and compared with echocardiographic measurements to discuss the validity of the method To reduce the risk of unintended confounding factors and to minimize the potential for bias several baseline data regarding the included research subjects will also be collected These variables include age years gender HM3 implantation date body mass index BMI kgm2 and cardiovascular diagnostic codes ICD-10 blood count cellsμL or x109L electrolytes mmolL liver function tests UL or µkatL for enzymes and gdL or µmolL for substances lactate dehydrogenase UL NT-proBNP pgmL or ngL and procalcitonin ngmL
24 DATA SOURCES AND MEASUREMENTS
241 PC-CT EXAMINATION PCCT-examinations will be performed utilizing a CE-marked photon-counting computed tomography system NAETOM Alpha Siemens Healthineer Erlangen Germany The acquisitions will be effectuated at 120 kVp with image quality IQ levels set at 70 A biphasic contrast administration protocol will be employed to guarantee opacification across all four cardiac chambers The entirety of the scan range will undergo multiphase reconstructions at intervals corresponding to every 5 of the cardiac cycle culminating in 20 distinct phases Acquired CT-images were relayed to the institutions Picture Archiving and Communication System PACS IDS7 Sectra Medical Systems Linkoping Sweden
242 SEGMENTATION AND WALL MOTION TRACKING
The motion of the endocardium will be tracked from the acquired CT-data In this process the endocardium will semi-automatically be outlined with ITK-SNAP version 380 The geometry will then be refined using Ansys SpaceClaim version 2019 R3 Ansys Inc Canonsburg PA 15317 USA Following this the endocardial surface will be reshaped using a non-rigid iterative closed point method to align with threshold-based segmentations from the remaining 19 cardiac phases
243 CFD SIMULATIONS
Blood flow velocity absolute pressure turbulence kinetic energy and blood stasis and other potential hemodynamic variables will be derived using Computational Fluid Dynamics CFD simulations considering the participant-specific cardiac wall motion The CFD simulations will be performed using Ansys Fluent version 2019 R3 based on the process previously validated using 4D flow MRI Two cardiac models will be applied The left model will include pulmonary veins left atrium left ventricle the HM3 outflow graft left ventricular outflow tract and ascending aorta The right model will include superior vena cava inferior vena cava right atrium right ventricle right ventricular outflow tract and the pulmonary artery All openings will be modelled as pressure openings with the flow rate resulting from the motion of the endocardium
243 PUMP VARIABLES AND BLOOD PRESSURE
Prior to every individual CT-scan estimated flow Lmin power W pulsatility index and rotor speed rpm will be acquired from the HeartMate 3 System Monitor together with systolic blood pressure mmHg acquired using doppler technology of the radial artery These details will be transferred to an established dataset within the project
245 ECHOCARDIOGRAPHY
Selected echocardiographic imaging will be conducted between each CT scan The specified protocol for the study is derived from the routine clinical protocol used to examine this patient group but is selected based on the time aspect of the full examination in the research project Clinical staff experienced in these examinations will perform the tests
246 PATIENT CHARACTERISTICS
Characteristic variables of the research subjects will be obtained from the medical record of the research subjects Furthermore results from the most recent clinical blood tests will be obtained These details will be transferred to an established dataset within the project
25 BIAS
Due to the exploratory nature of the study there are inherent risks of both systematic and non-systematic bias Firstly the variables to be studied are not entirely predefined at the outset due to the researchs exploratory design which may introduce bias To counteract this the decision-making process surrounding the inclusion or exclusion of emergent variables will be meticulously documented to ensure transparency and robustness in the research methodology Another significant consideration in this study is the use of CFD simulations These simulations while powerful in modeling fluid dynamics within the cardiovascular system are susceptible to biases based on the input parameters boundary conditions and numerical methods employed The chosen mesh resolution turbulence models and assumptions about blood rheology can all influence the results To bolster the validity of the quantified CFD results a key validation attempt in this study is the inclusion of echocardiography assessments However the echocardiographic image quality will vary between patients which in itself can introduce bias and impair the possibilities for adequate validation of the CFD simulations
26 STUDY SIZE
Determining the requisite sample size for this project is a challenge due to the method not having been previously evaluated Given this context the investigators have thus drawn upon the available literature from echocardiography studies and attempted to derive clinically significant differences based on pump settings from this The study aims to recruit up to 35 participants to ensure interpretable results
27 STATISTICAL METHODS
Inter-group comparisons will be performed using two-sample t-test To assess the association between variables such as CFD-variables and geometrical parameters linear regression analysis will be performed All statistical computations will be done using MATLAB R2021b and the significance level will be set at 5
In recent years the use of the mechanical circulatory support device HeartMate 3 HM3 Abbott Laboratories Lake Forest IL has garnered significant attention in the realm of circulatory support for advanced heart failure The tangible advantages of the HM3 including enhanced hemocompatibility leading to reduced thromboembolic events and improved survival rates compared to its predecessors The transition towards HM3 is particularly noteworthy as the system is not only likely to serve as a bridge to heart transplantation or decision-making but is increasingly being discussed as an effective destination therapy Despite these advancements there remains an imperative for meticulous hemodynamic monitoring throughout any mechanical circulatory support treatment Traditionally echocardiography has been predominantly employed as the hemodynamic imaging modality However echocardiographic evaluations of these patients present notable challenges especially concerning shadows from the pumps metal making it difficult to fully comprehend cardiac function and hemodynamics during the treatment
Over the past decade computed tomography CT has seen rapid advancements with modern equipment now facilitating high-resolution anatomical imaging of the heart throughout the cardiac cycle 4D CT Until recently however CT also posed a challenge for the examination of patients with mechanical circulatory support devices due to significant metal artifacts The newly introduced photon-counting computed tomography PC-CT however now enables scans that yield higher resolution images with reduced metal artifacts From time-resolved CT functional information can subsequently be derived and extracted Techniques for automatic tracking of cardiac wall motion throughout the cardiac cycle along with the utilization of computational dynamics to numerically solve fluid mechanical equations have previously been shown which have proven to enable simulations of intracardiac hemodynamic maps
The increasing indications for treatment with mechanical circulatory support underscore the current demand for continuously improved care quality and clinical understanding of this therapeutic option Although the treatment enhances both prognosis and quality of life serious and fatal complications remain recurrent To the knowledge of the investigators there has yet been no conducted research addressing the potential application of the novel PC-CT in patients with mechanical circulatory support devices and certainly none that have established numerical frameworks on this data in an attempt to compute visualize and exploratively understand intracardiac hemodynamics during the treatment
12 OBJECTIVES
121 AIM
The aim of this observational study is to exploratively investigate intracardiac geometry and hemodynamics in patients with ongoing HeartMate 3-therapy in the Swedish Southeast Healthcare region
122 PRIMARY SCIENTIFIC QUESTION
How do different flow levels in the HeartMate 3 left ventricular assist device influence intracardiac geometry and hemodynamics
2 METHODS
21 STUDY DESIGN
This study has an explorative analytic multiple cross-sectional design The study seeks to uncover new insights patterns and associations within the data partly without predetermined hypotheses Further the study investigates relationships or associations between variables to derive meaningful conclusions from the data The study will examine three distinct observations of the variables wherein the subjects device settings will vary These observations however will be executed in close temporal proximity with intervals of approximately 15 minutes between each As such while the study does not fully conform to the criteria of a multiple cross-sectional study design it also does not align with a traditional one-time-point cross-sectional approach
22 OVERALL SETTING
Participating research subjects are called upon to undergo three followed PC-CT scans as well as certain echocardiographic imaging all in one session The research subjects HM3 is connected to software that allows for variations in the pumps flow between these image collections All examinations will be performed at Center for Medical Image Science and Visualization CMIV at Linköping University Sweden Recruitment and examination within the study will undergo during January-December 2023 The study has been approved by the Swedish ethics review authority Reference number 2022-06934-01
22 PARTICIPANTS
All patients within the Swedish Southeastern healthcare region encompassing Östergötland Jönköping and Kalmar counties who meet the inclusion criteria and none of the exclusion criteria will be invited to participate in this study during 2023 Screening for inclusion is conducted by the LVAD-responsible physicians within the Cardiology Department at Linköping University Hospital
23 VARIABLES
Regarding specification of variables that will be studied it is essential to clarify that due to the exploratory nature of the research and the intricate dynamics inherent to both using numerical frameworks for calculating intracardiac hemodynamic maps and the dynamic geometric nature of time-resolved CT all variables at the study onset are not pre-defined As the analysis progresses and the full depth of the data becomes apparent additional variables may be identified and incorporated Subsequent decision-making process relating to the inclusion or exclusion of these newly discovered variables will be rigorously documented to ensure transparency and robustness in the study approach
Quantified variables will be compared with respect to the pumps estimated flow Lmin power W pulsatility index and rotor speed rpm Whenever possible based on image quality the results will also be related to and compared with echocardiographic measurements to discuss the validity of the method To reduce the risk of unintended confounding factors and to minimize the potential for bias several baseline data regarding the included research subjects will also be collected These variables include age years gender HM3 implantation date body mass index BMI kgm2 and cardiovascular diagnostic codes ICD-10 blood count cellsμL or x109L electrolytes mmolL liver function tests UL or µkatL for enzymes and gdL or µmolL for substances lactate dehydrogenase UL NT-proBNP pgmL or ngL and procalcitonin ngmL
24 DATA SOURCES AND MEASUREMENTS
241 PC-CT EXAMINATION PCCT-examinations will be performed utilizing a CE-marked photon-counting computed tomography system NAETOM Alpha Siemens Healthineer Erlangen Germany The acquisitions will be effectuated at 120 kVp with image quality IQ levels set at 70 A biphasic contrast administration protocol will be employed to guarantee opacification across all four cardiac chambers The entirety of the scan range will undergo multiphase reconstructions at intervals corresponding to every 5 of the cardiac cycle culminating in 20 distinct phases Acquired CT-images were relayed to the institutions Picture Archiving and Communication System PACS IDS7 Sectra Medical Systems Linkoping Sweden
242 SEGMENTATION AND WALL MOTION TRACKING
The motion of the endocardium will be tracked from the acquired CT-data In this process the endocardium will semi-automatically be outlined with ITK-SNAP version 380 The geometry will then be refined using Ansys SpaceClaim version 2019 R3 Ansys Inc Canonsburg PA 15317 USA Following this the endocardial surface will be reshaped using a non-rigid iterative closed point method to align with threshold-based segmentations from the remaining 19 cardiac phases
243 CFD SIMULATIONS
Blood flow velocity absolute pressure turbulence kinetic energy and blood stasis and other potential hemodynamic variables will be derived using Computational Fluid Dynamics CFD simulations considering the participant-specific cardiac wall motion The CFD simulations will be performed using Ansys Fluent version 2019 R3 based on the process previously validated using 4D flow MRI Two cardiac models will be applied The left model will include pulmonary veins left atrium left ventricle the HM3 outflow graft left ventricular outflow tract and ascending aorta The right model will include superior vena cava inferior vena cava right atrium right ventricle right ventricular outflow tract and the pulmonary artery All openings will be modelled as pressure openings with the flow rate resulting from the motion of the endocardium
243 PUMP VARIABLES AND BLOOD PRESSURE
Prior to every individual CT-scan estimated flow Lmin power W pulsatility index and rotor speed rpm will be acquired from the HeartMate 3 System Monitor together with systolic blood pressure mmHg acquired using doppler technology of the radial artery These details will be transferred to an established dataset within the project
245 ECHOCARDIOGRAPHY
Selected echocardiographic imaging will be conducted between each CT scan The specified protocol for the study is derived from the routine clinical protocol used to examine this patient group but is selected based on the time aspect of the full examination in the research project Clinical staff experienced in these examinations will perform the tests
246 PATIENT CHARACTERISTICS
Characteristic variables of the research subjects will be obtained from the medical record of the research subjects Furthermore results from the most recent clinical blood tests will be obtained These details will be transferred to an established dataset within the project
25 BIAS
Due to the exploratory nature of the study there are inherent risks of both systematic and non-systematic bias Firstly the variables to be studied are not entirely predefined at the outset due to the researchs exploratory design which may introduce bias To counteract this the decision-making process surrounding the inclusion or exclusion of emergent variables will be meticulously documented to ensure transparency and robustness in the research methodology Another significant consideration in this study is the use of CFD simulations These simulations while powerful in modeling fluid dynamics within the cardiovascular system are susceptible to biases based on the input parameters boundary conditions and numerical methods employed The chosen mesh resolution turbulence models and assumptions about blood rheology can all influence the results To bolster the validity of the quantified CFD results a key validation attempt in this study is the inclusion of echocardiography assessments However the echocardiographic image quality will vary between patients which in itself can introduce bias and impair the possibilities for adequate validation of the CFD simulations
26 STUDY SIZE
Determining the requisite sample size for this project is a challenge due to the method not having been previously evaluated Given this context the investigators have thus drawn upon the available literature from echocardiography studies and attempted to derive clinically significant differences based on pump settings from this The study aims to recruit up to 35 participants to ensure interpretable results
27 STATISTICAL METHODS
Inter-group comparisons will be performed using two-sample t-test To assess the association between variables such as CFD-variables and geometrical parameters linear regression analysis will be performed All statistical computations will be done using MATLAB R2021b and the significance level will be set at 5
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None