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

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.

Study Overview

• Status: Recruiting
• Conditions: Takotsubo Cardiomyopathy
• Intervention / Treatment: Drug: No medications; Drug: Bisoprolol; Drug: Valsartan; Drug: sacubitril/ valsartan; Drug: Dapagliflozin (10mg Tab)

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jennifer Ramsay; Phone Number: 01316501000; Email: jramsay5@ed.ac.uk

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom
    • Recruiting
    • University of Edinburgh
    • Contact: Jennifer Ramsay; Phone Number: 01316501000; Email: jramsay5@ed.ac.uk
    • Principal Investigator: Jennifer Ramsay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Acute cohort - no medication; 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.	Drug: No medications; Participants will be randomised to receive no study medication.
Active Comparator: Acute cohort - Bisoprolol; Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy within the last 3 months and will be randomized to receive Bisoprolol.	Drug: Bisoprolol; Participants will be randomised to receive Bisoprolol medication.
Active Comparator: Acute cohort - Valsartan; Participants in this arm will have had a diagnosis of takotsubo cardiomyopathy within the last 3 months and will be randomized to receive Valsartan.	Drug: Valsartan; Participants will be randomised to receive Valsartan medication.
Active Comparator: Chronic cohort - Sacubitril/Valsartan first; 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.	Drug: sacubitril/ valsartan; Participants will be randomised to receive Sacubitril/Valsartan medication first.
Active Comparator: Chronic cohort - Dapaglifozin first; 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.	Drug: Dapagliflozin (10mg Tab); Participants will be randomised to receive Dapaglifozin medication first.
No Intervention: Healthy Volunteers; Healthy volunteers will not receive any intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Left ventricular myocardial manganese uptake.	2 years

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: University of Edinburgh

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2025
• Primary Completion (Estimated): August 9, 2028
• Study Completion (Estimated): August 9, 2028

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Manganese; Takotsubo; Stress cardiomyopathy; Broken heart syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Cardiomyopathies; Ventricular Dysfunction; Ventricular Dysfunction, Left; Takotsubo Cardiomyopathy; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Amines; Amino Acids; Alcohols; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Amino Acids, Essential; Tetrazoles; Valine; Amino Acids, Branched-Chain; Valsartan; Bisoprolol; sacubitril and valsartan sodium hydrate drug combination; dapagliflozin
• Other Study ID Numbers: 348948; PG/24/11930 (Other Grant/Funding Number: BHF)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No