An observational study in Heart Failure, sponsored by Region Östergötland. Recruiting at 1 site in Sweden. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-11-02.
Sponsored by Region Östergötland · Observational
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:
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 subject's HeartMate device is connected to software that allows for variations in the pump's 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.
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 pump's 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.
1.2 OBJECTIVES
1.2.1 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.
1.2.2 PRIMARY SCIENTIFIC QUESTION
How do different flow levels in the HeartMate 3 left ventricular assist device influence intracardiac geometry and hemodynamics?
2.1 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.
2.2 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 subject's HM3 is connected to software that allows for variations in the pump's 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).
2.2 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.
2.3 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 pump's estimated flow (L/min), 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, kg/m\^2), and cardiovascular diagnostic codes (ICD-10), blood count (cells/μL or x10\^9/L), electrolytes (mmol/L), liver function tests (U/L or µkat/L for enzymes, and g/dL or µmol/L for substances), lactate dehydrogenase (U/L), NT-proBNP (pg/mL or ng/L), and procalcitonin (ng/mL).
2.4 DATA SOURCES AND MEASUREMENTS
2.4.1 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 institution's Picture Archiving and Communication System (PACS, IDS7, Sectra Medical Systems, Linköping, Sweden).
2.4.2 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 3.8.0). 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.
2.4.3 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.
2.4.3 PUMP VARIABLES AND BLOOD PRESSURE
Prior to every individual CT-scan, estimated flow (L/min), 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.
2.4.5 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.
2.4.6 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.
2.5 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 research's 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.
2.6 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.
2.7 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%.
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's planned enrollment of 35 is below the median of 200 across 1,983 observational studies indexed under Heart Failure.
Browse Heart Failure studies →Region Östergötland is the lead sponsor of 29 studies on the registry; 8 are open to participants now.
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All HeartMate 3 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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemodynamic Variables
Intracardiac hemodynamic variables such as blood flow velocity maps (m/s), absolute pressure maps (mmHg), turbulence kinetic energy maps (TKE), and blood stasis maps will be calculated both intracardiac and in the pump's outflow graft. 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.
Time frame: Observations are made at a single point in time. No follow-up of outcomes are analyzed. Post-processing and analysis of both hemodynamic and geometric data are performed through study completion, an average of 1 year.
Intracardiac Geometry
Intracardiac volumes (ml) will be calculated for the left atrium, left ventricle, right ventricle and right atrium over the cardiac cycle (20 phases). 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.
Time frame: Observations are made at a single point in time. No follow-up of outcomes are analyzed. Post-processing and analysis of both hemodynamic and geometric data are performed through study completion, an average of 1 year.
Plan to share: No
Started Mar 2023 (actual). Primary completion is estimated for Jan 2030, 82 months after the start.
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Region Östergötland