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| ID | Type | Description | Link |
|---|---|---|---|
| PG/24/11930 | Other Grant/Funding Number | BHF |
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The goal of this research study is to further understand the physiological mechanisms involved in a heart condition called takotsubo cardiomyopathy, also known as broken heart syndrome. Furthermore, the investigators will be assessing the effects different cardiac medications have on these physiological mechanisms.
This will be achieved by performing cardiac MRI scans using a special dye called manganese. Manganese uptake in the heart is altered in patients with takotsubo cardiomyopathy. The investigators will study the effects that different cardiac medications have on manganese uptake.
Takotsubo cardiomyopathy is a medical condition which presents similarly to a heart attack. It is usually caused by physical or emotional stress and typically affects women aged 50-74. It causes sudden severe impairment in heart muscle function, which was previously thought to get better in a matter of weeks. However, 1 in 10 patients will die in hospital and those that recover have substantially reduced long-term survival. There is no definitive treatment for takotsubo cardiomyopathy at present. Standard heart scans carried out in clinical care suggest that takotsubo cardiomyopathy gets better within a few weeks. However, patients don't always feel better at this stage.
Researchers at the University of Edinburgh have previously demonstrated that performing an MRI scan of the heart using a special dye called manganese shows that changes in the heart muscle persist for months to years after the original diagnosis of takotsubo cardiomyopathy. The investigators propose to assess the effects of established heart failure therapy on patients with takotsubo cardiomyopathy, specifically the effects this has on manganese-enhanced MRI scans.
Participants will be divided into two study groups based on the timing of their diagnoses. Participants with a recent diagnosis less than 3 months ago will be allocated to receive Bisoprolol, Valsartan or no medication. Participants with a diagnosis more than 6 months ago will be allocated to receive Sacubitril/Valsartan or Dapaglifozin for 3 months then will change to the alternative medication for 3 months with a 1-month wash-out period in between. Participants will attend for study visits every few weeks-months to assess the effects of the medication. At the study visits the participants will undergo a range of investigations including the manganese-enhanced MRI scan, echocardiogram, ECG, walking test and blood tests. Furthermore, participants will undergo a clinical assessment by the study doctor and be asked to complete a symptom questionnaire.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute cohort - no medication | Placebo Comparator | Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy within the last 3 months and will be randomized to receive no medication. |
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| Acute cohort - Bisoprolol | Active Comparator | Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy within the last 3 months and will be randomized to receive Bisoprolol. |
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| Acute cohort - Valsartan | Active Comparator | Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy within the last 3 months and will be randomized to receive Valsartan. |
|
| Chronic cohort - Sacubitril/Valsartan first | Active Comparator | Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy more than 6 months ago. They will be randomised to receive Sacubitril/Valsartan first for a 3 month period then switch onto Dapaglifozin for 3 months with a 1 month wash out period in between. |
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| Chronic cohort - Dapaglifozin first | Active Comparator | Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy more than 6 months ago. They will be randomised to receive Dapaglifozin first for a 3 month period then switch onto Sacubitril/Valsartan for 3 months with a 1 month wash out period in between. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bisoprolol | Drug | Participants will be randomised to receive Bisoprolol medication. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Left ventricular myocardial manganese uptake. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Assessing effects of renin-angiotensin system inhibition and beta-adrenoreceptor blockade on myocardial manganese uptake. | 2 years | |
| Assessing effects of angiotensin receptor/neprilysin inhibition and sodium-glucose co-transporter 2 inhibition on myocardial manganese uptake. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jennifer Ramsay | Contact | 01316501000 | jramsay5@ed.ac.uk |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Edinburgh | Recruiting | Edinburgh | United Kingdom |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 4, 2025 | Jan 8, 2026 | Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: Study 2 - Chronic Cohort | Sep 9, 2025 | Jan 8, 2026 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: Study 1 - Acute Cohort | Sep 9, 2025 | Jan 8, 2026 | ICF_002.pdf |
| ICF | No | No | Yes | Informed Consent Form: Healthy Volunteers | Sep 9, 2025 | Jan 8, 2026 | ICF_003.pdf |
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| ID | Term |
|---|---|
| D054549 | Takotsubo Cardiomyopathy |
| ID | Term |
|---|---|
| D009202 | Cardiomyopathies |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D018487 | Ventricular Dysfunction, Left |
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| ID | Term |
|---|---|
| D017298 | Bisoprolol |
| D000068756 | Valsartan |
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
| C529054 | dapagliflozin |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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This will be a prospective randomised open-label blinded endpoint (PROBE) study design with additional use of a cross-over design.
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|
| Healthy Volunteers | No Intervention | Healthy volunteers will not receive any intervention. |
| Valsartan | Drug | Participants will be randomised to receive Valsartan medication. |
|
| sacubitril/ valsartan | Drug | Participants will be randomised to receive Sacubitril/Valsartan medication first. |
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| Dapagliflozin (10mg Tab) | Drug | Participants will be randomised to receive Dapaglifozin medication first. |
|
| No medications | Drug | Participants will be randomised to receive no study medication. |
|
| 2 years |
| Assessing the effects of cardiovascular risk factors on myocardial manganese uptake. | 2 years |
| Correlation of neurohumoral markers and myocardial manganese uptake. | 2 years |
| Correlations between myocardial manganese uptake and self-reported symptoms and objective assessments of exercise capacity in Takotsubo Cardiomyopathy. | 2 years |
| D018754 |
| Ventricular Dysfunction |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014633 | Valine |
| D000597 | Amino Acids, Branched-Chain |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |