Multiparametric MRI for Fabry Cardiomyopathy

(FIESTA-MRI Trial)

Overseen By Kate Hanneman

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Myocardial infarction, MRI contraindication

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

250 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Cardiac MRI for Fabry Cardiomyopathy?

Cardiac MRI is effective in diagnosing and monitoring Fabry cardiomyopathy by measuring heart function, volume, and mass, and detecting early signs of heart involvement, which helps in managing the disease and improving patient outcomes. ^{1 2 3 4 5}

Is cardiac MRI safe for humans?

Cardiac MRI is generally safe, but some people may experience mild reactions to the contrast agent used, like gadolinium, which can cause temporary side effects. It's important to note that people with certain heart devices, like pacemakers, need special precautions during the procedure. ^{6 7 8 9 10}

How is cardiac MRI used as a treatment for Fabry cardiomyopathy different from other treatments?

Cardiac MRI is unique for Fabry cardiomyopathy because it is a noninvasive imaging technique that helps diagnose and monitor the disease by assessing heart structure and function, and detecting early signs of heart involvement, unlike other treatments that may focus on managing symptoms or enzyme replacement. ^{2 3 4 11 12}

What is the purpose of this trial?

This study will evaluate whether cardiac MRI T1 and T2 mapping improves our ability to detect early abnormalities in the heart in patients with Fabry disease and identify patients at increase risk of adverse events.

Research Team

Kate Hanneman, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults over 18 with Fabry disease, aiming to detect early heart issues. It's not suitable for those who've had a heart attack or can't undergo MRI scans due to health risks or implanted medical devices.

Inclusion Criteria

I have Fabry disease.

Exclusion Criteria

I have had a heart attack before.

You cannot have an MRI for medical reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cardiac MRI and Biomarker Assessment

Participants undergo cardiac MRI, ECG, and blood biomarker assessments to detect early myocardial abnormalities

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for major adverse cardiac events and changes in the FASTEX score

5 years

Periodic visits (in-person)

Treatment Details

Interventions

• Cardiac MRI

Trial Overview The study tests if advanced cardiac MRI techniques can spot early signs of heart damage in Fabry patients and predict future complications better than traditional methods.

Participant Groups

Group I: Cardiac MRI, ECG and Blood Biomarkers Experimental Treatment 1 Intervention

Additional sequences will be performed during routine clinical cardiac MRI and additional blood samples will be collected during routine blood work.

Cardiac MRI is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Cardiac MRI for:

• Congenital heart disease
• Cardiomyopathies
• Valvular heart disease
• Diseases of the aorta
• Coronary heart disease
• Cardiac tumors

Approved in United States as Cardiac MRI for:

• Coronary heart disease
• Congenital heart defects
• Heart valve problems
• Pericarditis
• Cardiac tumors
• Myocardial infarction

Approved in Canada as Cardiac MRI for:

• Cardiomyopathies
• Valvular heart disease
• Diseases of the aorta
• Coronary heart disease
• Cardiac tumors
• Myocardial infarction

Approved in Japan as Cardiac MRI for:

• Congenital heart disease
• Cardiomyopathies
• Valvular heart disease
• Diseases of the aorta
• Coronary heart disease

Approved in China as Cardiac MRI for:

• Congenital heart disease
• Cardiomyopathies
• Valvular heart disease
• Diseases of the aorta
• Coronary heart disease

Approved in Switzerland as Cardiac MRI for:

• Congenital heart disease
• Cardiomyopathies
• Valvular heart disease
• Diseases of the aorta
• Coronary heart disease

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

IRCCS Policlinico S. Donato

Collaborator

Trials

102

Recruited

108,000+

Alberta Health services

Collaborator

Trials

168

Recruited

658,000+

Libin Cardiovascular Institute of Alberta

Collaborator

Trials

4

Recruited

650+

Vancouver General Hospital

Collaborator

Trials

42

Recruited

19,700+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Findings from Research

Cardiac magnetic resonance feature tracking (CMR-FT) effectively identifies myocardial dysfunction in Fabry disease (FD) patients, showing significant reductions in global longitudinal strain (GLS) across all stages of the disease compared to healthy controls.

The study, involving 20 FD patients and 20 healthy controls, indicates that CMR-FT can track disease severity, with the most severe myocardial impairment observed in patients with advanced disease stages, suggesting its potential as a valuable tool for monitoring FD progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantification of myocardial deformation in patients with Fabry disease by cardiovascular magnetic resonance feature tracking imaging. Zhao, L., Zhang, C., Tian, J., et al.[2022]

Cardiac MRI is essential for diagnosing cardiac involvement in Fabry disease, as it helps assess heart function, volume, and mass, which are critical for evaluating patient prognosis.

Measuring native myocardial T1 values through cardiac MRI can lead to early detection of cardiac issues, while tracking left ventricular myocardial mass can help monitor treatment effectiveness in patients with Fabry disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Role of Cardiac MRI in the Diagnosis of Fabry Disease]. Hong, YJ., Kim, YJ.[2022]

Fabry disease is a rare genetic disorder caused by a deficiency of the α-galactosidase A enzyme, leading to harmful accumulation of certain substances in various organs, particularly affecting the heart and kidneys.

Early diagnosis and treatment of Fabry disease are crucial to prevent serious complications like heart failure, and cardiovascular magnetic resonance imaging plays a key role in diagnosing and monitoring the effectiveness of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac MRI in Fabry disease. Umer, M., Kalra, DK.[2023]

Fabry disease (FD) is a genetic condition that can lead to serious heart issues, including left ventricular hypertrophy (LVH) and heart failure, making early diagnosis essential for effective treatment.

Multimodality cardiac imaging techniques, such as echocardiography and cardiovascular magnetic resonance, are crucial for diagnosing FD and monitoring its progression, helping differentiate it from other causes of LVH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fabry Disease: More than a Phenocopy of Hypertrophic Cardiomyopathy. Stankowski, K., Figliozzi, S., Battaglia, V., et al.[2023]

In a study of 55 patients with Fabry disease followed for about 4.9 years, 16.3% experienced serious cardiac events, highlighting the importance of monitoring heart health in these patients.

Maximal wall thickness (MWT) was identified as a strong independent predictor of cardiac events, suggesting that measuring LVH through cardiac MRI can help assess risk and guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and CMR characteristics associated with cardiac events in patients with Fabry disease. Hiestand, R., Nowak, A., Sokolska, JM., et al.[2023]

In a study of 1334 cardiovascular magnetic resonance (CMR) procedures for patients with congenital heart disease, the overall incidence of adverse events (AEs) was low at 1.6%, with most being minor in severity.

The use of general anesthesia and the status of being an inpatient were identified as independent risk factors for experiencing AEs, particularly in the most critically ill patients, highlighting the need for careful monitoring in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events during cardiovascular magnetic resonance in congenital heart disease. Dorfman, AL., Odegard, KC., Powell, AJ., et al.[2013]

The MagnaSafe Registry is a large-scale study aiming to evaluate the safety of performing MRI on patients with non-MRI-conditional cardiac devices, involving up to 1500 MRI examinations to assess adverse events and device changes.

As of August 2012, 701 MRI studies have been completed, indicating significant progress in understanding the risks associated with MRI in patients with implanted pacemakers or defibrillators, which could lead to more informed clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the risks of clinically indicated nonthoracic magnetic resonance imaging at 1.5 T for patients with pacemakers and implantable cardioverter-defibrillators: rationale and design of the MagnaSafe Registry. Russo, RJ.[2022]

In a study involving 17,767 patients across 45 European centers, only 30 acute adverse reactions (0.17%) were reported after administering gadolinium-based contrast agents during cardiac magnetic resonance imaging, all classified as mild.

The most common reactions included rashes, hives, nausea, and anxiety, with the incidence of adverse events being comparable to that seen in general radiology settings, indicating that the off-label use of these agents in CMR is safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patients from the EuroCMR Registry. Bruder, O., Schneider, S., Nothnagel, D., et al.[2016]

Cardiovascular magnetic resonance (CMR) scans can be safely performed in non-pacemaker dependent patients with pacemakers, as demonstrated in 6 scans involving 5 patients, with careful monitoring and reprogramming of the devices.

The scans provided valuable diagnostic information without significant complications, although one incident occurred where a pacemaker began pacing at maximum voltage, which was managed without any adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular magnetic resonance at 0.5T in five patients with permanent pacemakers. Heatlie, G., Pennell, DJ.[2006]

In a study of 72,839 patients undergoing gadolinium-enhanced cardiac magnetic resonance imaging, the incidence of acute adverse events (AAEs) was low at 0.36%, with severe AAEs occurring in only 0.033% of cases.

AAE rates were influenced by factors such as the type of gadolinium-based contrast agent used, the presence of pharmacological stress during imaging, and the specific indications for the imaging, with higher rates observed during stress imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute adverse events in cardiac MR imaging with gadolinium-based contrast agents: results from the European Society of Cardiovascular Radiology (ESCR) MRCT Registry in 72,839 patients. Uhlig, J., Lücke, C., Vliegenthart, R., et al.[2021]

Anderson-Fabry disease (AFD) leads to serious long-term heart issues, including left ventricular hypertrophy and myocardial fibrosis, which can cause complications like arrhythmias and coronary artery disease.

Cardiac magnetic resonance (CMR) imaging is crucial for diagnosing and monitoring heart involvement in AFD, utilizing advanced techniques like myocardial strain and T1/T2 mapping to assess heart function and tissue health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced CMR Techniques in Anderson-Fabry Disease: State of the Art. Ponsiglione, A., De Giorgi, M., Ascione, R., et al.[2023]

In a study of 40 patients with Fabry disease and hypertrophic cardiomyopathy, 3D late gadolinium enhancement (LGE) MRI provided comparable results to the traditional 2D MRI for quantifying myocardial fibrosis, indicating its diagnostic reliability.

The 3D imaging technique significantly reduced acquisition time (25 seconds) compared to the 2D method (349 seconds), making it a faster and more efficient option for assessing myocardial fibrosis in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative comparison of 2D and 3D late gadolinium enhancement MR imaging in patients with Fabry disease and hypertrophic cardiomyopathy. Morsbach, F., Gordic, S., Gruner, C., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

Quantification of myocardial deformation in patients with Fabry disease by cardiovascular magnetic resonance feature tracking imaging. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

[The Role of Cardiac MRI in the Diagnosis of Fabry Disease]. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiac MRI in Fabry disease. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Fabry Disease: More than a Phenocopy of Hypertrophic Cardiomyopathy. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical and CMR characteristics associated with cardiac events in patients with Fabry disease. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events during cardiovascular magnetic resonance in congenital heart disease. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Determining the risks of clinically indicated nonthoracic magnetic resonance imaging at 1.5 T for patients with pacemakers and implantable cardioverter-defibrillators: rationale and design of the MagnaSafe Registry. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patients from the EuroCMR Registry. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Cardiovascular magnetic resonance at 0.5T in five patients with permanent pacemakers. [2006]

10. Germany pubmed.ncbi.nlm.nih.gov

Acute adverse events in cardiac MR imaging with gadolinium-based contrast agents: results from the European Society of Cardiovascular Radiology (ESCR) MRCT Registry in 72,839 patients. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Advanced CMR Techniques in Anderson-Fabry Disease: State of the Art. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Quantitative comparison of 2D and 3D late gadolinium enhancement MR imaging in patients with Fabry disease and hypertrophic cardiomyopathy. [2022]