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Cardiac transthyretin amyloidosis (ATTR), caused by ventricular depositions of misfolded transthyretin, results in an infiltrative cardiomyopathy, progressing from pronounced myocardial wall thickening, diastolic and systolic dysfunction to the development of terminal heart failure. Recently, treatment options for TTR amyloidosis have become available. However costs for therapy are enormous and previous trials were not able to differentiate between patients that might benefit from treatment and those without a need for treatment.
the investigators study aims to determine markers, as assessed by cardiac magnet resonance imaging (CMR) feature tracking (FT) and T1- and T2- mapping, that might reliably indicate disease severity and could help to identify patients that might benefit from (ongoing) TTR stabilization treatment.
Cardiac transthyretin amyloidosis (ATTR), the most common amyloidosis form with cardiac involvement, is caused by tissue deposition of misfolded TTR, a transport Protein for thyroxine and retinol. Ventricular depositions of amyloid fibrils results in an infiltrative cardiomyopathy, progressing from pronounced myocardial wall thickening, to diastolic and systolic dysfunction and finally chronic heart failure.
While treatment options are now available, it remains unclear how to monitor therapy response and disease progression. No makers have been identified that predict outcome prior to initiation of therapy, thus patient selection for therapy remains challenging.
The investigators study will address these issues and will provide systematically assessed CMR data before and over the course of 18 months after therapy initiation. Clinical and laboratory follow-up will be performed every 3-6 months. The investigators study is based on an open, uncontrolled, structured collection of retrospective and prospective data from all patients diagnosed with amyloidosis at the Inselspital Bern with the aim to follow patients undergoing therapy.
The investigators hypothesize that CMR feature tracking (FT) and measures of T1- and T2- mapping, such as extracellular volume (ECV) may better correlate with disease severity and help to identify patients likely to benefit from (ongoing) TTR stabilizing therapy. Beside standard CMR assessments, the investigators will use CMR feature tracking to quantify global and regional myocardial function. FT has proven to be an excellent predictor in various cardiomyopathies.
The proposed study will evaluate the potential of CMR to identify patients likely to benefit from therapy, monitor treatment response and balance individual patient benefit and health care cost.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with confirmed amyloidosis | Confirmed diagnosis of amyloidosis w/wo cardiac involvement |
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| Measure | Description | Time Frame |
|---|---|---|
| LV (left ventricle) and RV (right ventricle) function as assessed by CMR feature tracking as predictor for MACE (major adverse cardiac event) | Global and regional longitudinal (%), circumferential (%) and radial (%) strain measurements are used to quantify LV and RV function before and after therapy initiation. MACE is defined as a composite of sustained ventricular tachycardia, hospitalization for heart failure and all-cause death. | 5 years |
| LV and RV tissue characterization as assessed by T1 and T2 mapping as predictor for MACE | Global and regional tissue characteristics are assessed by repetitive T1 and T2 mapping (global and regional T1 and T2 time (ms)) before and during therapy. MACE is defined as a composite of major cardiovascular endpoints listed above. | 5 years |
| Late gadolinium enhancement as predictor for MACE | Global and regional myocardial tissue is characterized by gadolinium contrast agent application. The presence and extent (% and total mass (g)) of late gadolinium enhancement is evaluated as a predictor for MACE. | 5 years |
| Extracellular volume (ECV) as predictor for MACE | ECV (%) as a marker of myocardial tissue remodelling is calculated from native and post-contrast T1 mapping and haematocrit before and during therapy. | 5 years |
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Inclusion Criteria:
Exclusion Criteria:
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Confirmed diagnosis of amyloidosis w/wo cardiac involvement
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Christoph Gräni, MD, PhD | Contact | +41 31 632 4508 | christoph.graeni@insel.ch | |
| Moritz Hundertmark, MD, PhD | Contact | +41 31 63 2 40 86 | moritz.hundertmark@insel.ch |
| Name | Affiliation | Role |
|---|---|---|
| Christoph Gräni, MD, PhD | Department of Cardiology, University Hospital Bern, Inselspital, Bern | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USB | Not yet recruiting | Basel | 4031 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41804669 | Derived | Caobelli F, Popescu CE, Gozlugol N, Rominger A, Zangeneh FA, Munsch LH, Ciocca N, Stortecky S, Dobner S, Hundertmark M, Grani C. Correlation of global and regional quantitative 99m Tc-3,3-diphosphono-1,2 propanodicarboxylicacid single-photon emission computed tomography with echocardiography in patients with suspected transthyretin-related cardiomyopathy. Nucl Med Commun. 2026 Jun 1;47(6):638-643. doi: 10.1097/MNM.0000000000002138. Epub 2026 Mar 10. | |
| 38724281 |
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| ID | Term |
|---|---|
| D028227 | Amyloid Neuropathies, Familial |
| D013180 | Sprains and Strains |
| ID | Term |
|---|---|
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D009422 | Nervous System Diseases |
| D017772 | Amyloid Neuropathies |
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Genetic testing is a part of the routine diagnostic work-up of TTR amyloidosis patients. Current knowledge suggests that therapy response and clinical outcome may differ in TTR patients suffering from wt-TTR and h-/m-TTR-amyloidosis, respectively. Therefore, the genetic background should also be assessed as part of the registry.
| Department of Cardiology, University Hospital Bern, Inselspital, Bern | Recruiting | Bern | 3010 | Switzerland |
|
| HUG | Recruiting | Geneva | 1211 | Switzerland |
|
| CHUV | Recruiting | Lausanne | 1011 | Switzerland |
|
| LUKS | Recruiting | Lucerne | 6000 | Switzerland |
|
| KSSG | Recruiting | Sankt Gallen | 9007 | Switzerland |
|
| Stadtspital Triemli | Recruiting | Zurich | 8063 | Switzerland |
|
| Derived |
| Caobelli F, Gozlugol N, Bakula A, Rominger A, Schepers R, Stortecky S, Hunziker Munsch L, Dobner S, Grani C. Prognostic Value of [99mTc]Tc-DPD Quantitative SPECT/CT in Patients with Suspected and Confirmed Amyloid Transthyretin-Related Cardiomyopathy and Preserved Left Ventricular Function. J Nucl Med. 2024 Jun 3;65(6):944-951. doi: 10.2967/jnumed.123.266926. |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028226 | Amyloidosis, Familial |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000686 | Amyloidosis |
| D057165 | Proteostasis Deficiencies |
| D014947 | Wounds and Injuries |