Amyloidosis CardiacCAUSATIVENCT06066632
Analysis of Calcium Score of Severe Aortic Stenosis in Patients With and Without Cardiac Amyloidosis (CAUSATIVE Study)
An observational study of Amyloidosis Cardiac and Aortic Stenosis, Severe, run by University Hospital of Ferrara at 1 site in Italy.
Trial summary
The concomitant presence of cardiac amyloidosis (CA) in patients with aortic stenosis (AS) may challenge the estimation of stenosis degree. In patients with dual pathology (AS + CA) the most frequent AS hemodynamic profile is paradoxical low-flow, low-gradient AS. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Amyloidosis Cardiac, Aortic Stenosis, Severe
- How many people
- 480 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jun 2023to 1 Jun 2024
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: Group 1 "DUAL PATHOLOGY" * Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * Cardiac uptake at bone tracer scintigraphy with a Perugini score of 2 or 3. Group 2 "CONTROL GROUP" * Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * patients with no cardiac uptake at scintigraphy with bone tracer.
Who may be able to join
- signed informed consent
- age ≥65 years old
- severe AS
- planned or performed TAVI/SAVR
- at least one red-flag suggestive of CA
- availability of EKG-gated CT
- availability of echocardiogram performed before TAVI/SAVR
- availability of bone scintigraphy performed within 1 year from CT
Who cannot join
- suboptimal acoustic window that may undermine the assessment of AS severity and phenotype profiling
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
University Hospital of Ferrara
Ferrara, 44124
Matteo Serenelli, Doctor, 0532236269, m.serenelli@ospfe.it
Paolo Cimaglia, Doctor, 0532236269, paolo.cimaglia@ospfe.it
About this study
Official title: Analysis of Calcium Score Values of Severe Aortic Stenosis in Patients With and Without Cardiac Amyloidosis (CAUSATIVE Study)
The concomitant presence of cardiac amyloidosis (CA) in patients with aortic stenosis (AS) may challenge the estimation of stenosis degree. In patients with dual pathology (AS + CA) the most frequent AS hemodynamic profile is paradoxical low-flow, low-gradient AS.
In this setting, estimating stenosis degree with cardiac ultrasound may be challenging and aortic valve calcium score estimation by cardiac CT is a valuable exam.
Read more
Preliminary findings from small case series showed that patients with severe AS and CA presented less valvular calcium deposition compared to patients with severe AS alone. On this basis, confirmation of these findings would have a huge clinical impact on diagnosis, choice of treatment strategy and understanding of the pathophysiology of these patients.
The aim of the study is to study the correlation between valvular calcium score (assessed by EKG-gated CT) and effective orifice area (assessed through echocardiogram) according to cardiac amyloidosis presence (in the overall population and among hemodynamic phenotypes of cardiac amyloidosis).
As secondary endpoints the study will sought to assess TAVI/SAVR efficacy, procedural complications, in-hospital mortality, all-cause death and heart failure hospitalization at 1 year, according to absence or presence of CA.
Read the detailed description
Aortic stenosis (AS) is the most common valvular pathology in the elderly population, and there is an anticipated increase in prevalence and associated costs for treating this condition in the future. In a non-negligible percentage of cases (approximately 15%), another pathology is associated, namely cardiac amyloidosis, especially in the wild-type ATTR form. Patients with both pathologies (AS+ATTR) have a worse prognosis compared to those with AS alone. Based on the available data up to now, ATTR-associated amyloidotic cardiomyopathy does not appear to significantly influence the immediate outcome of TAVI or short-term outcomes. However, among patients with amyloidosis, there is an increased frequency of heart failure in subsequent follow-ups. The mechanism behind this dual pathology remains unclear. Epidemiological similarities (advanced age) alone do not explain the association. It is possible that there is a direct causal link between amyloidosis and aortic stenosis (amyloidosis as a co-cause or contributing factor to valvular stenosis), or that the elevated intramyocardial strain due to degenerative valvular stenosis promotes amyloidogenesis and myocardial infiltration. Understanding the extent of valvular calcifications in individual cases would provide better insights into the pathogenesis of this dual pathology. There are also diagnostic implications. Amyloidosis could potentially complicate the accurate classification of the severity of aortic pathology. For example, patients with AS+ATTR often exhibit a "low-flow low-gradient" paradoxical hemodynamic profile. In these cases, estimating the valve area with an echocardiogram is challenging, and evaluating the valvular calcium score through CT assumes an important diagnostic role. Preliminary studies suggest that, for the same degree of stenosis severity, there may be a lower quantity of calcium in the valves of patients with AS+ATTR compared to those with AS alone. Preliminary studies suggest that, for the same degree of stenosis severity, there may be a lower quantity of calcium in the valves of patients with AS+ATTR compared to those with AS alone. In a 1:1 propensity matching of over 300 patients (mostly without aortic stenosis), those with amyloidosis had lower aortic valvular calcium scores (p<0.01). In a small series of 13 cases with AS+ATTR, 12 had aortic valvular calcium scores below the severity cut-offs recommended by the guidelines. If confirmed, traditionally used calcium score cut-offs may be inadequate, with significant implications for treatment selection and therefore prognosis.
- Conditions
- Amyloidosis Cardiac, Aortic Stenosis, Severe
- Keywords
- Amyloidosis, Aortic stenosis, Calcium Score, Low-flow low-gradient
- Medical subject headings
- Amyloid Neuropathies, Familial, Aortic Valve Stenosis, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - "Dual Pathology" | * Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * Cardiac uptake at bone tracer scintigraphy with a Perugini score of 2 or 3. | |
| Group 2- "Control Group" | * Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * Patients with no cardiac uptake at scintigraphy with bone tracer. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between valvular calcium score and effective orifice area.
Correlation between valvular calcium score (assessed by EKG-gated CT) and effective orifice area (assessed through echocardiogram) according to cardiac amyloidosis presence (in the overall population and among hemodynamic phenotypes of cardiac amyloidosis).
Measured: Up to 12 months
Secondary outcomes (5)
TAVI/SAVR efficacy
Echocardiographic mean and maximal aortic gradient (mmHg) will be assessed.
Measured: At time of post-procedural echocardiographic assessment (through study completion, an average of 1 month)
TAVI/SAVR efficacy
Echocardiographic effective orifice valvular area (EROA) will be assessed and reported in cm2.
Measured: At time of post-procedural echocardiographic assessment (through study completion, an average of 1 month)
Procedural Complications
Procedural complications will be assessed as per VARC definitions
Measured: At an average of 12 months
In-hospital Mortality
In-hospital Mortality will be assessed from hospital records
Measured: At an average of 12 months
All-cause Mortality and Heart Failure Hospitalization
The composite of all-cause Mortality and Heart Failure Hospitalization will be assessed through clinical follow-up, hospital records, and telephone follow-up.
Measured: At an average of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2023
- Study start1 Jun 2023
- Primary completion1 May 2024 (estimated)
- Study completion1 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Amyloidosis CardiacStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 480 participants (estimated)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- University Hospital of Ferrara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matteo Serenelli, University Hospital of Ferrara
- Investigators
- Matteo Serenelli, Doctor, Principal investigator, Azienda Ospedaliero Universitaria di Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06066632
- Sponsor's protocol ID
- 72/2022/Oss/AOUFe
- Acronym
- CAUSATIVE
- Status last verified
- Sep 2023
- First submitted
- 15 Sep 2023
- Last updated
- 4 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The data will be available from the principal investigator on reasonable request.
Publications
Hussan et al. Aortic Valve Calcium Score Cut-Offs Used To Identify Hemodynamically Severe Aortic Stenosis May Not Apply In Patients With Cardiac Amyloidosis. ACC.20 World Congress of Cardiology (https://www.jacc.org/doi/abs/10.1016/S0735-1097%2820%2932791-1)
Hussain M, Hanna M, Griffin BP, Conic J, Patel J, Fava AM, Watson C, Phelan DM, Jellis C, Grimm RA, Rodriguez LL, Schoenhagen P, Hachamovitch R, Jaber WA, Cremer PC, Collier P. Aortic Valve Calcium in Patients With Transthyretin Cardiac Amyloidosis: A Propensity-Matched Analysis. Circ Cardiovasc Imaging. 2020 Oct;13(10):e011433. doi: 10.1161/CIRCIMAGING.120.011433. Epub 2020 Sep 23. No abstract available.
PubMed 32967445
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Calcium Score Values of Severe Aortic Stenosis in Patients With and Without Cardiac Amyloidosis (CAUSATIVE Study)
- ClinicalTrials.gov ID
- NCT06066632
- Acronym / sponsor ID
- CAUSATIVE / 72/2022/Oss/AOUFe
- Conditions
- Amyloidosis Cardiac, Aortic Stenosis, Severe
- Keywords
- Amyloidosis, Aortic stenosis, Calcium Score, Low-flow low-gradient
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 480 participants (estimated)
- Lead sponsor
- University Hospital of FerraraUniversity, hospital or other
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 1 May 2024 (estimated)
- Study completion
- 1 Jun 2024 (estimated)
- First posted
- 4 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The concomitant presence of cardiac amyloidosis (CA) in patients with aortic stenosis (AS) may challenge the estimation of stenosis degree. In patients with dual pathology (AS + CA) the most frequent AS hemodynamic profile is paradoxical low-flow, low-gradient AS.
In this setting, estimating stenosis degree with cardiac ultrasound may be challenging and aortic valve calcium score estimation by cardiac CT is a valuable exam.
Preliminary findings from small case series showed that patients with severe AS and CA presented less valvular calcium deposition compared to patients with severe AS alone. On this basis, confirmation of these findings would have a huge clinical impact on diagnosis, choice of treatment strategy and understanding of the pathophysiology of these patients.
The aim of the study is to study the correlation between valvular calcium score (assessed by EKG-gated CT) and effective orifice area (assessed through echocardiogram) according to cardiac amyloidosis presence (in the overall population and among hemodynamic phenotypes of cardiac amyloidosis).
As secondary endpoints the study will sought to assess TAVI/SAVR efficacy, procedural complications, in-hospital mortality, all-cause death and heart failure hospitalization at 1 year, according to absence or presence of CA.
Detailed description
Aortic stenosis (AS) is the most common valvular pathology in the elderly population, and there is an anticipated increase in prevalence and associated costs for treating this condition in the future. In a non-negligible percentage of cases (approximately 15%), another pathology is associated, namely cardiac amyloidosis, especially in the wild-type ATTR form. Patients with both pathologies (AS+ATTR) have a worse prognosis compared to those with AS alone. Based on the available data up to now, ATTR-associated amyloidotic cardiomyopathy does not appear to significantly influence the immediate outcome of TAVI or short-term outcomes. However, among patients with amyloidosis, there is an increased frequency of heart failure in subsequent follow-ups. The mechanism behind this dual pathology remains unclear. Epidemiological similarities (advanced age) alone do not explain the association. It is possible that there is a direct causal link between amyloidosis and aortic stenosis (amyloidosis as a co-cause or contributing factor to valvular stenosis), or that the elevated intramyocardial strain due to degenerative valvular stenosis promotes amyloidogenesis and myocardial infiltration. Understanding the extent of valvular calcifications in individual cases would provide better insights into the pathogenesis of this dual pathology. There are also diagnostic implications. Amyloidosis could potentially complicate the accurate classification of the severity of aortic pathology. For example, patients with AS+ATTR often exhibit a "low-flow low-gradient" paradoxical hemodynamic profile. In these cases, estimating the valve area with an echocardiogram is challenging, and evaluating the valvular calcium score through CT assumes an important diagnostic role. Preliminary studies suggest that, for the same degree of stenosis severity, there may be a lower quantity of calcium in the valves of patients with AS+ATTR compared to those with AS alone. Preliminary studies suggest that, for the same degree of stenosis severity, there may be a lower quantity of calcium in the valves of patients with AS+ATTR compared to those with AS alone. In a 1:1 propensity matching of over 300 patients (mostly without aortic stenosis), those with amyloidosis had lower aortic valvular calcium scores (p<0.01). In a small series of 13 cases with AS+ATTR, 12 had aortic valvular calcium scores below the severity cut-offs recommended by the guidelines. If confirmed, traditionally used calcium score cut-offs may be inadequate, with significant implications for treatment selection and therefore prognosis.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Target follow-up
- 12 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 - "Dual Pathology" | – | –* Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * Cardiac uptake at bone tracer scintigraphy with a Perugini score of 2 or 3. |
| Group 2- "Control Group" | – | –* Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * Patients with no cardiac uptake at scintigraphy with bone tracer. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- Group 1 "DUAL PATHOLOGY" * Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * Cardiac uptake at bone tracer scintigraphy with a Perugini score of 2 or 3. Group 2 "CONTROL GROUP" * Age >65 years * Severe aortic stenosis at echocardiographic examination * TAVI o SAVR planned or already undergone TAVI/SAVR * ECG-gated cardiac CT and echocardiographic examinations available before TAVI/SAVR * patients with no cardiac uptake at scintigraphy with bone tracer.
Key inclusion criteria (8 listed)
- signed informed consent
- age ≥65 years old
- severe AS
- planned or performed TAVI/SAVR
- at least one red-flag suggestive of CA
Key exclusion criteria (1 listed)
- suboptimal acoustic window that may undermine the assessment of AS severity and phenotype profiling
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation between valvular calcium score and effective orifice area.
Time frame: Up to 12 months
Correlation between valvular calcium score (assessed by EKG-gated CT) and effective orifice area (assessed through echocardiogram) according to cardiac amyloidosis presence (in the overall population and among hemodynamic phenotypes of cardiac amyloidosis).
5 secondary outcomes
TAVI/SAVR efficacy
Time frame: At time of post-procedural echocardiographic assessment (through study completion, an average of 1 month)
TAVI/SAVR efficacy
Time frame: At time of post-procedural echocardiographic assessment (through study completion, an average of 1 month)
Procedural Complications
Time frame: At an average of 12 months
In-hospital Mortality
Time frame: At an average of 12 months
All-cause Mortality and Heart Failure Hospitalization
Time frame: At an average of 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2023.
- BackgroundHussan et al. Aortic Valve Calcium Score Cut-Offs Used To Identify Hemodynamically Severe Aortic Stenosis May Not Apply In Patients With Cardiac Amyloidosis. ACC.20 World Congress of Cardiology (https://www.jacc.org/doi/abs/10.1016/S0735-1097%2820%2932791-1)
- Results publication: PubMed 32967445Hussain M, Hanna M, Griffin BP, Conic J, Patel J, Fava AM, Watson C, Phelan DM, Jellis C, Grimm RA, Rodriguez LL, Schoenhagen P, Hachamovitch R, Jaber WA, Cremer PC, Collier P. Aortic Valve Calcium in Patients With Transthyretin Cardiac Amyloidosis: A Propensity-Matched Analysis. Circ Cardiovasc Imaging. 2020 Oct;13(10):e011433. doi: 10.1161/CIRCIMAGING.120.011433. Epub 2020 Sep 23. No abstract available.
- Individual participant dataSharing planned: Undecided. The data will be available from the principal investigator on reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matteo Serenelli, Doctor principal investigator
Azienda Ospedaliero Universitaria di Ferrara
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amyloidosis Cardiac and Aortic Stenosis, Severe, run by University Hospital of Ferrara at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matteo Serenelli, Doctor (0532236269, m.serenelli@ospfe.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between valvular calcium score and effective orifice area. (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06066632, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2023.