Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06372301
Status:
RECRUITING
Last Update Posted:
2024-04-18
First Post:
2024-04-15
Brief Title:
Dobutamine Stress Echocardiography in LFLG Aortic Stenosis and Wild-type Transthyretin Amyloid Cardiomyopathy
Sponsor:
Steen Hvitfeldt Poulsen
Organization:
Aarhus University Hospital Skejby
Study Overview
Official Title:
Utility of Dobutamine Stress Echocardiography in the Diagnosis of Severe Aortic Stenosis in Patients With Low-flow Low-gradient and Co-exiting Wild-type Transthyretin Amyloid Cardiomyopathy
Status:
RECRUITING
Status Verified Date:
2024-04
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:
DobAttrAS
Brief Summary:
The goal of this prospective clinical study is improve the diagnosis of Low-flow low-gradient aortic stenosis LFLG AS in patients with co-existing wild-type transthyretin cardiac amyloidosis ATTRwt The main question it aims to answer is whether the classic dobutamine-stress echocardiography can be used to determine AS severity in patients with ATTRwt and LFLG AS This question will be tried to answer by comparing dobutamine stress echocardiography with the invasively measured aortic valve area which is considered as the gold standard
In addition we aim to assess the degree of myocardial fibrosis and amyloid infiltration assessed by light microscopy and cardiac magnetic resonance CMRI and evaluation of myocyte mitochondrial function by high resolution respirometry and their relation to AS severity and hemodynamic response to dobutamine
In addition we aim to assess the degree of myocardial fibrosis and amyloid infiltration assessed by light microscopy and cardiac magnetic resonance CMRI and evaluation of myocyte mitochondrial function by high resolution respirometry and their relation to AS severity and hemodynamic response to dobutamine
Detailed Description:
Study protocol
A- Baseline assessment The following will be measured
Blood pressure and heart rate
ECG
Standard echocardiography
Dobutamine stress echocardiography
B- Catheterization laboratory The participant will be transferred to the catheterization laboratory after about 15-hour recovery period after the end of dobutamine stress echocardiography The following will be done in the following order
Right heart catheterization and endomyocardial biopsies
Left heart catheterization
Dobutamine challenge Infusion of increasing dobutamine dosages with simultaneous invasive measurements
Removal of left and right heart catheters The catheters will be removed after 5 minutes recovery after dobutamine challenge
C- Observation The participant will then be transferred to our out-patient hospital for observation and the participant is expected to be discharged after 2 hours of observation if no complications arise
D- CMRI All the participants will be evaluated with CMRI for estimation of LV mass T-1 values and extracellular volume ECV This will be scheduled for a separate visit
Investigations and procedures
1 Dobutamine Challenges
Dobutamine challenge will be performed two times at the trial day The first dobutamine challenge will be performed immediately after the baseline echocardiographic examination The second dobutamine challenge will be performed no earlier than 2 hours later at the catherization laboratory as described below Dobutamine known for its brief half-life of approximately 2 minutes ensures that its effects diminish rapidly and the specified two-hour interval guarantees that its influence has subsided
A ramp dobutamine infusion will be performed with a stepwise dobutamine dosage increase dosages 2351020 ugkgmin Dobutamine dosage will only be increased to 40 ugkgmin in patients with ongoing beta-blocker treatment to ensure an appropriate dobutamine response
The first dobutamine challenge with echocardiography Blood pressure heart rate and standard echocardiography images will be obtained before the infusion start at each infusion stage and during the recovery period after the infusion is omitted The projected aortic valve area AVAproj is calculated by using the simplified formula
AVAproj AVArest AVApeak- AVArest Qpeak-Qrest x 250- Qrest
Q is defined as the transvalvular flow rate SVEjection time SV is calculated by the LVOTVTI x LVOTarea Ejection time is measured by CW-Doppler of the valve profile
The second dobutamine challenge with invasive measurements This will be performed at the catheterization laboratory after the insertion of right and left heart catheters There must be a minimum of 2 hours between the two dobutamine challenges Blood pressure heart rate and pressure and flow measurements will be obtained before the infusion start at each infusion stage and during the recovery period after the infusion is omitted AVA will be estimated at rest and at each dobutamine dose level using Gorlin formulaThe abovementioned equation for AVAproj will be also used to calculate AVAproj from the invasive measurements
2 Endomyocardial biopsies and biobank Before the right and left heart catheterization are initiated three endomyocardial biopsies will be taken from the interventricular septum through the internal jugular vein access or femoral vein The first biopsy is for evaluation of mitochondrial function by high resolution respirometry The other two biopsies are for semi-quantitative evaluation of fibrosis and amyloid infiltration by standard diagnostic light microscopy at the department of pathology at Aarhus University Hospital Any residual tissue from the first biopsy to respirometry will be destroyed after completing the analysis The biopsies for light microscopy will be prepared analyzed and stored in clinical biobank according to the standard clinical practice at the department of pathology
3 High Resolution Respirometry Biopsies used for high resolution respirometry are analyzed immediately after being taken High resolution respirometry is performed at the unit of Clinical Research Department of Cardiology at Aarhus University Hospital The procedure is standard in the department
4 Cardiac Magnetic Resonance Imaging CMRI CMRI scan will be performed to assess LV mass fibrosis assessed as late gadolinium enhancement ECV assessed using T1-mapping LV volume left and right ventricular ejection fraction and strain mapping analysis Gadolinium-based contrast will not be administered to participants with an estimated Glomerular Filtration Rate eGFR 30 mlmin173 m2 due to the risk of adverse effects
A- Baseline assessment The following will be measured
Blood pressure and heart rate
ECG
Standard echocardiography
Dobutamine stress echocardiography
B- Catheterization laboratory The participant will be transferred to the catheterization laboratory after about 15-hour recovery period after the end of dobutamine stress echocardiography The following will be done in the following order
Right heart catheterization and endomyocardial biopsies
Left heart catheterization
Dobutamine challenge Infusion of increasing dobutamine dosages with simultaneous invasive measurements
Removal of left and right heart catheters The catheters will be removed after 5 minutes recovery after dobutamine challenge
C- Observation The participant will then be transferred to our out-patient hospital for observation and the participant is expected to be discharged after 2 hours of observation if no complications arise
D- CMRI All the participants will be evaluated with CMRI for estimation of LV mass T-1 values and extracellular volume ECV This will be scheduled for a separate visit
Investigations and procedures
1 Dobutamine Challenges
Dobutamine challenge will be performed two times at the trial day The first dobutamine challenge will be performed immediately after the baseline echocardiographic examination The second dobutamine challenge will be performed no earlier than 2 hours later at the catherization laboratory as described below Dobutamine known for its brief half-life of approximately 2 minutes ensures that its effects diminish rapidly and the specified two-hour interval guarantees that its influence has subsided
A ramp dobutamine infusion will be performed with a stepwise dobutamine dosage increase dosages 2351020 ugkgmin Dobutamine dosage will only be increased to 40 ugkgmin in patients with ongoing beta-blocker treatment to ensure an appropriate dobutamine response
The first dobutamine challenge with echocardiography Blood pressure heart rate and standard echocardiography images will be obtained before the infusion start at each infusion stage and during the recovery period after the infusion is omitted The projected aortic valve area AVAproj is calculated by using the simplified formula
AVAproj AVArest AVApeak- AVArest Qpeak-Qrest x 250- Qrest
Q is defined as the transvalvular flow rate SVEjection time SV is calculated by the LVOTVTI x LVOTarea Ejection time is measured by CW-Doppler of the valve profile
The second dobutamine challenge with invasive measurements This will be performed at the catheterization laboratory after the insertion of right and left heart catheters There must be a minimum of 2 hours between the two dobutamine challenges Blood pressure heart rate and pressure and flow measurements will be obtained before the infusion start at each infusion stage and during the recovery period after the infusion is omitted AVA will be estimated at rest and at each dobutamine dose level using Gorlin formulaThe abovementioned equation for AVAproj will be also used to calculate AVAproj from the invasive measurements
2 Endomyocardial biopsies and biobank Before the right and left heart catheterization are initiated three endomyocardial biopsies will be taken from the interventricular septum through the internal jugular vein access or femoral vein The first biopsy is for evaluation of mitochondrial function by high resolution respirometry The other two biopsies are for semi-quantitative evaluation of fibrosis and amyloid infiltration by standard diagnostic light microscopy at the department of pathology at Aarhus University Hospital Any residual tissue from the first biopsy to respirometry will be destroyed after completing the analysis The biopsies for light microscopy will be prepared analyzed and stored in clinical biobank according to the standard clinical practice at the department of pathology
3 High Resolution Respirometry Biopsies used for high resolution respirometry are analyzed immediately after being taken High resolution respirometry is performed at the unit of Clinical Research Department of Cardiology at Aarhus University Hospital The procedure is standard in the department
4 Cardiac Magnetic Resonance Imaging CMRI CMRI scan will be performed to assess LV mass fibrosis assessed as late gadolinium enhancement ECV assessed using T1-mapping LV volume left and right ventricular ejection fraction and strain mapping analysis Gadolinium-based contrast will not be administered to participants with an estimated Glomerular Filtration Rate eGFR 30 mlmin173 m2 due to the risk of adverse effects
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