Manganese-enhanced Magnetic Resonance Imaging in Takotsubo Cardiomyopathy (TAKO MEMRI)

University of Edinburgh

Status: Enrolling

Conditions: Takotsubo Cardiomyopathy

Treatments: Drug: Dapagliflozin (10mg Tab); Drug: Valsartan; Drug: sacubitril/ valsartan; Drug: No medications; Drug: Bisoprolol

Study type: Interventional

Funder types: Other

Identifiers

NCT07491718

PG/24/11930 (Other Grant/Funding Number)

348948

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Males and females >18 years of age
• Clinical presentation of takotsubo cardiomyopathy
• Have capacity to give formal consent

Exclusion criteria

• Unable to tolerate or contraindication to magnetic resonance imaging
• Renal failure (estimated glomerular filtration rate <30 mL/min/1.73 m2) - this would be assessed by performing a blood test
• Prior history of cardiomyopathy
• Current pregnancy
• Weight greater than 250kg
• Severe asthma for study 1 (given Bisoprolol is contraindicated in this condition)
• Type 1 diabetes mellitus for study 2 (given Dapaglifozin is contraindicated in this population)
• Significant hypotension (given the medications prescribed as part of the study can also cause hypotension as a side effect)
• Significant bradycardia for study 1 (given Bisoprolol can exacerbate any pre-existing significant bradycardia)
• Prescribed Digoxin (this medication interacts with the Manganese)
• Unable to give formal consent

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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100 participants in 6 patient groups, including a placebo group

Acute cohort - no medication

Placebo Comparator group

Description:

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.

Treatment:

Drug: No medications

Acute cohort - Bisoprolol

Active Comparator group

Description:

Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy within the last 3 months and will be randomized to receive Bisoprolol.

Treatment:

Drug: Bisoprolol

Acute cohort - Valsartan

Active Comparator group

Description:

Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy within the last 3 months and will be randomized to receive Valsartan.

Treatment:

Drug: Valsartan

Chronic cohort - Sacubitril/Valsartan first

Active Comparator group

Description:

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.

Treatment:

Drug: sacubitril/ valsartan

Chronic cohort - Dapaglifozin first

Active Comparator group

Description:

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.

Treatment:

Drug: Dapagliflozin (10mg Tab)

Healthy Volunteers

No Intervention group

Description:

Healthy volunteers will not receive any intervention.