Life-style Interventions for Modulating the Brain Phenotype of Takotsubo Cardiomyopathy

Study Overview
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Brief Summary
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Takotsubo cardiomyopathy presents like a heart attack and is typically triggered by intense emotional or physical stress. Recovery of this condition varies and many patients continue to suffer from symptoms such as fatigue and breathlessness for a protracted period after their event. The purpose of this study is to establish whether following a structured exercise program or a mental wellbeing program compared to usual care for 12 weeks after an episode of Takotsubo will result in significant improvement in the brain activity, general and mental wellbeing of patients.

Detailed Description
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Takotsubo cardiomyopathy is characterised by sudden onset left ventricular dysfunction precipitated by major stress. This neuro-cardiac condition has a 5-year morbidity and mortality comparable with acute myocardial infarction and no current therapies exist. The psycho-somatic basis of Takotsubo suggests that its neuro-biology could be amenable to modulation. Here, the investigators propose a mechanistic three-arm pilot feasibility trial of standardised physical exercise training, cognitive behavioural therapy and current standard of care in patients who suffered a very recent episode of takotsubo cardiomyopathy.

Official Title
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Life-Style Interventions for Modulating the Brain Phenotype of Takotsubo Cardiomyopathy - the BREAKOUT Study

Conditions
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Takotsubo Cardiomyopathy

Intervention / Treatment
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* Other: Exercise program
* Other: Cognitive behavioural therapy
* Other: Standard clinical care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with takotsubo cardiomyopathy in the previous three weeks Participant who is willing and able to give informed consent for participation in the study. Participant who is willing to travel to Aberdeen Royal Infirmary for the study visits. Healthy volunteers (for blood and saliva samples only) willing to give informed consent for participation in the study. Healthy volunteers should not be on any medication. For influenza T-Cell testing: healthy volunteers who have recently received their annual flu vaccination. Myocardial Infarction (MI) comparators: patients with type 1 acute MI (diagnosed within the last three weeks) Exclusion Criteria: Any patient whose takotsubo cardiomyopathy was triggered by a physical illness that would preclude them from taking part in a physical exercise training program Any patient who is not able or willing to travel to the cardiovascular research facility for their study visits Any patient who is not able to commit to a 12 week supervised training program Inability to exercise on a cycle ergometer or a treadmill (e.g. use of walking aids or prosthetic limbs or advanced frailty) Unwillingness to participate Contraindication to MRI scanning such as implantable cardiac devices. Pregnancy Healthy volunteers taking medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Three arm pilot feasibility study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>Takotsubo patients receiving standard care | Other: Standard clinical care<br>* Standard clinical care<br>|
| Active Comparator: Exercise Group<br>Takotsubo patients who will undergo an exercise program in addition to standard care | Other: Exercise program<br>* Exercise program<br>Other: Standard clinical care<br>* Standard clinical care<br>|
| Active Comparator: CBT Group<br>Takotsubo patients who will receive cognitive behavioural therapy in addition to standard care | Other: Cognitive behavioural therapy<br>* Cognitive behavioural therapy<br>Other: Standard clinical care<br>* Standard clinical care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hippocampal volume change | Brain Magnetic Resonance Imaging | At ≤3 weeks of diagnosis of takotsubo cardiomyopathy and repeated at completion of 12 weeks intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mental wellbeing testing | Eysenck personality questionnaires, Hospital Anxiety and Depression, Perceived Stress Scale and Work & Social Adjustment | At ≤3 weeks of diagnosis of takotsubo cardiomyopathy and repeated at completion of 12 weeks intervention | 
| Mental wellbeing testing | Blood will be collected for PBMCs isolation and serum cytokine levels | At ≤3 weeks of diagnosis of takotsubo cardiomyopathy and repeated at completion of 12 weeks intervention | 
| Mental wellbeing test | Cortisol Awakening Response | At ≤3 weeks of diagnosis of takotsubo cardiomyopathy and repeated at completion of 12 weeks intervention | 
| Exercise Capacity | 6 minute walk test and Cardiopulmonary Exercise Test | At ≤3 weeks of diagnosis of takotsubo cardiomyopathy and repeated at completion of 12 weeks intervention | 
| Cardiac Imaging | Echocardiography | At ≤3 weeks of diagnosis of takotsubo cardiomyopathy and repeated at completion of 12 weeks intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Takotsubo Cardiomyopathy